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The ExTINGUISH Trial of Inebilizumab in NMDAR Encephalitis (ExTINGUISH)
Determine the difference in the modified Rankin score at 16 weeks in participants with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis treated with "first-line" immunomodulatory therapies provided as standard-of-care, and either inebilizumab (investigational agent) or placebo.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Taylor.Hinojo@UTSouthwestern.edu
Kyle Blackburn
ALL
12 Years and over
PHASE2
NCT04372615
STU-2021-1105
Inclusion Criteria
• Diagnosis of NMDAR encephalitis, defined by both a and b:
• A subacute onset of change in mental status consistent with autoimmune encephalitis,
• A positive cell-based assay for anti-NMDA receptor IgG antibody in the CSF confirmed in study-specified laboratories.
• Participants, ≥ 12 years of age at the time of informed consent. Participants under 18 years of age must weigh ≥40 kilograms.
• Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act \[HIPAA\] in the United States of America \[USA\], European Union \[EU\] Data Privacy Directive in the EU) obtained from the participant/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Non-sterilized participants who are sexually active with a partner capable of becoming pregnant must use a condom with spermicide from Day 1 through to the end of the study and must agree to continue using such precautions for at least 6 months after the final dose of IP. A recommendation will be made that the partners (capable of becoming pregnant) of study participants (capable of getting their partner pregnant) should use a highly effective method of contraception other than a physical method. Participants of childbearing potential who are sexually active with a non-sterilized partner capable of getting their partner pregnant must agree to use a highly effective method of contraception beginning at screening or upon discharge from hospitalization/inpatient rehabilitation (for participants who were incapacitated at the time of screening), and to continue precautions for 12 months after the final dose of IP.
• Participants of childbearing potential are defined as those who are not surgically sterile (e.g., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or those who are not postmenopausal (per ICH M3 (R2) 11.2: defined as 12 months with no menses without an alternative medical cause).
• A highly effective method of contraception is defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. Periodic abstinence, the rhythm method, and the withdrawal method do not qualify as "highly effective" or acceptable methods of contraception for study purposes. Acceptable methods of contraception are listed in the table below: Physical Methods Hormonal Methods e • Intrauterine device (IUD) • Intrauterine hormone-releasing system, also known as drug-eluting IUD a • Bilateral tubal occlusion • Vasectomized partner b • Sexual abstinence c • Combined (estrogen and progestogen-containing hormonal contraception) * Oral (combined pill) * Injectable * Transdermal (patch) * Progestogen-only hormonal contraception associated with inhibition of ovulation d * Implantable * Intravaginal a This is also considered to be a hormonal method. b With appropriate post-vasectomy documentation of surgical success (absence of sperm in ejaculate). c Sexual abstinence is considered to be a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of the study and if it is the preferred and usual lifestyle of the participant. d Progestogen-only hormonal contraception, where inhibition of ovulation is not the primary mode of action (minipill) is not accepted as a highly effective method. e These methods are only considered highly effective and therefore acceptable when used in conjunction with a barrier method (i.e., diaphragm with spermicide, sponge with spermicide, cervical cap with spermicide, condoms, spermicide alone.)
• Willing to forgo other immunomodulatory therapies (investigational or otherwise) for NMDAR encephalitis during the study.
• Participant must have received at least 3 days of methylprednisolone 1000 mg IV or equivalent corticosteroid within 90 days prior to randomization (Day 1). In addition, participants must have received EITHER of the following treatments within 90 days before randomization.
• IVIg, at a dose range between 1.2 and 2 g/kg
• Plasma exchange or plasmapheresis, (defined as 5 to 6 exchanges). NOTE: These treatments may be provided during the screening period but must be completed prior to randomization. Participants who receive methylprednisolone and BOTH IVIg and plasma exchange are not excluded from participating in the trial, however, this treatment course with both IVIg and plasma exchange is not encouraged, and enrollment and randomization should not be delayed in order to complete additional first line treatments.
• Modified Rankin Score of ≥3 at the screening visit, indicating at least moderate disability. The baseline mRS must be confirmed by Site Investigators at screening and confirmed / adjudicated before randomization.
• Ability and willingness to attend study visits and complete the study. \*All inclusion criteria must be met during the screening period, prior to randomization, except where noted. Exclusion Criteria Any of the following excludes an individual from participation in the study:
• Any condition that, in the opinion of the Investigator, would interfere with the evaluation or administration of the IP, interpretation of participant safety or study results, or would make participation in the study an unacceptable risk. This specifically includes recent history (last 5 years) of herpes simplex virus encephalitis or known central nervous system demyelinating disease (e.g., multiple sclerosis).
• Presence of an active or chronic infection that is serious in the opinion of the Investigator.
• History of solid organ or cell-based transplantation.
• Concurrent/previous enrollment in another clinical study involving an investigational treatment within 4 weeks or 5 published half-lives of the investigational treatment, whichever is longer, prior to randomization.
• Lactating or pregnant individuals, or individuals who intend to become pregnant anytime from study enrollment to 12 months following last dose of investigational agent.
• Known history of allergy or reaction to any component of the investigational agent formulation or history of anaphylaxis following any biologic therapy.
• Receipt of the following at any time prior to randomization: a. Alemtuzumab b. Total lymphoid irradiation c. Bone marrow transplant d. T-cell vaccination therapy
• Receipt of any biologic B cell-depleting therapy (e.g., rituximab, ocrelizumab, obinutuzumab, ofatumumab, inebilizumab) in the 6 months prior to screening. Receipt of such a B cell-depleting agent in the period 6-12 months prior to screening is exclusionary unless B cell counts have returned to ≥ age-based LLN by central laboratory. For EU participants, B cell counts at screening will be determined by the laboratories of the participating sites. Receipt of non-depleting B cell-directed therapy (e.g., belimumab), abatacept, or other biologic immunomodulatory agent within 6 months prior screening.
• Treatment at therapeutic doses/durations with any of the following within 3 months prior to randomization a. Natalizumab (Tysabri®) b. Cyclosporine c. Methotrexate d. Mitoxantrone e. Cyclophosphamide\* f. Azathioprine g. Mycophenolate mofetil \*Cyclophosphamide is only permitted as rescue therapy to be administered as outlined in Section 5.4.1 no earlier than the week 6 visit.
• Severe drug allergic history or anaphylaxis to two or more food products or medicines (including known sensitivity to acetaminophen/paracetamol, diphenhydramine (cetirizine in EU) or equivalent antihistamine, and methylprednisolone or equivalent glucocorticoid).
• Known history of a primary immunodeficiency (congenital or acquired) or an underlying condition such as human immunodeficiency virus (HIV) infection or splenectomy that predisposes the participant to infection.
• Active malignancy or history of malignancy that was active within the last 10 years, apart from ovarian or extra-ovarian teratoma (also known as a dermoid cyst) or germ cell tumor, or squamous cell carcinoma of the skin or basal cell carcinoma of the skin, that in the opinion of the Medical Safety Monitor (MSM) would preclude enrollment due to safety concerns. Squamous cell and basal cell carcinomas should be treated with documented success of curative therapy \> 3 months prior to randomization.
• At screening (repeat testing may be conducted to confirm results within the same screening period, prior to randomization), any of the following: a. Total white blood count \<2,500 cells/mm3 (or \< 2.5 × 109/L) b. Total immunoglobulin \< 600 mg/dL (or 6 µmol/L; 400 mg/dL for participants \<18 years)\* c. Absolute neutrophil count \< 1200 cells/μL (or \< 1.2 × 109/L) d. CD4 T lymphocyte count \< 300 cells/µL (or \< 0.3 × 109/L) \*Baseline levels of IgG prior to first line treatments (methylprednisolone, plasmapheresis/plasma exchange) should be used to determine eligibility.
• Active hepatitis B or C established with positive hepatitis B serology (hepatitis B surface antigen and core antigen) and/or positive hepatitis C PCR testing and confirmed by the MSM
• Any live or attenuated vaccine within 4 weeks prior to Day 1 (administration of killed vaccines is acceptable).
• Bacillus of Calmette and Guérin (BCG) vaccine within 1 year of enrollment.
• History of alcohol or drug abuse that, in the opinion of the Investigator, might affect participant safety or compliance with visits or interfere with safety or other study assessments.
• Recurrence of previously treated NMDAR encephalitis within the last 5 years, or suspicion of symptomatic untreated NMDAR encephalitis of greater than 3 months duration at the time of screening.
• Evidence of active tuberculosis\* (TB) or being at high risk for TB based on: a. History of active TB or untreated/incompletely treated latent TB. Participants with a history of active or latent TB who have documentation of completion of treatment according to local guidelines may be enrolled. b. History of recent (≤ 12 weeks of screening) close contact with someone with active TB (close contact is defined as ≥ 4 hours/week OR living in the same household OR in a house where a person with active TB is a frequent visitor). c. Signs or symptoms that could represent active TB by medical history or physical examination. d. Positive, indeterminate, or invalid interferon-gamma release assay test result at screening, unless previously treated for TB. Participants with an indeterminate test result can repeat the test once, but if the repeat test is also indeterminate, the participant is excluded. e. Chest radiograph, chest computed tomography or MRI scan that suggests a possible diagnosis of TB or suggests that a work-up for TB should be considered; all participants must have had lung imaging with an acceptable reading within 6 months prior to consent, or during screening.
• Active, clinically significant (CS) infection at the time of randomization (IP administration may be delayed until recovery, if within 14-day screening window, otherwise participant may be rescreened). Exclusion criteria are applied at time of screening and are applicable throughout the study. * Participants will undergo QuantiFERON®-TB Gold testing or equivalent TB testing during screening as standard of care. A positive result will not exclude patients from participation; thus, enrollment should not be delayed awaiting this result. If positive, an appropriate course of anti-TB treatment will need to be documented. If results are in indeterminate, participants may still be eligible for randomization if history is not suggestive of active / latent TB and a chest x-ray shows no evidence of active or latent TB.
• 1 Additional Eligibility Considerations The following criteria are not necessarily exclusionary but require review from the MSM to determine if a participant should be excluded due to safety concerns:
• At screening (out of range lab values may be reviewed with the MSM to determine whether a potential participant should be excluded for safety reasons; repeat testing may be conducted to confirm results within the same screening period, prior to randomization), any of the following:
• Aspartate transaminase (AST) \> 2.5 × age-based upper limit of normal (ULN)
• Alanine transaminase (ALT) \> 2.5 × age-based ULN
• Total bilirubin \> 1.5 × age-based ULN (unless due to Gilbert's syndrome)
• Platelet count \< 75,000/μL (or \< 75 × 109/L)
• Hemoglobin \< 8 g/dL (or \< 80 g/L or 5 mmol/L)
• History of untreated hepatitis C infection. Participants who are considered cured following antiviral therapy with an HCV load below the limit of detection may be enrolled pending confirmation from the MSM that there are no safety concerns for inclusion.
• Patients with coexistent autoantibodies should not immediately be excluded but should be reviewed with the MSM to determine eligibility.
• Diagnosis of NMDAR encephalitis, defined by both a and b:
• A subacute onset of change in mental status consistent with autoimmune encephalitis,
• A positive cell-based assay for anti-NMDA receptor IgG antibody in the CSF confirmed in study-specified laboratories.
• Participants, ≥ 12 years of age at the time of informed consent. Participants under 18 years of age must weigh ≥40 kilograms.
• Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act \[HIPAA\] in the United States of America \[USA\], European Union \[EU\] Data Privacy Directive in the EU) obtained from the participant/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Non-sterilized participants who are sexually active with a partner capable of becoming pregnant must use a condom with spermicide from Day 1 through to the end of the study and must agree to continue using such precautions for at least 6 months after the final dose of IP. A recommendation will be made that the partners (capable of becoming pregnant) of study participants (capable of getting their partner pregnant) should use a highly effective method of contraception other than a physical method. Participants of childbearing potential who are sexually active with a non-sterilized partner capable of getting their partner pregnant must agree to use a highly effective method of contraception beginning at screening or upon discharge from hospitalization/inpatient rehabilitation (for participants who were incapacitated at the time of screening), and to continue precautions for 12 months after the final dose of IP.
• Participants of childbearing potential are defined as those who are not surgically sterile (e.g., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or those who are not postmenopausal (per ICH M3 (R2) 11.2: defined as 12 months with no menses without an alternative medical cause).
• A highly effective method of contraception is defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. Periodic abstinence, the rhythm method, and the withdrawal method do not qualify as "highly effective" or acceptable methods of contraception for study purposes. Acceptable methods of contraception are listed in the table below: Physical Methods Hormonal Methods e • Intrauterine device (IUD) • Intrauterine hormone-releasing system, also known as drug-eluting IUD a • Bilateral tubal occlusion • Vasectomized partner b • Sexual abstinence c • Combined (estrogen and progestogen-containing hormonal contraception) * Oral (combined pill) * Injectable * Transdermal (patch) * Progestogen-only hormonal contraception associated with inhibition of ovulation d * Implantable * Intravaginal a This is also considered to be a hormonal method. b With appropriate post-vasectomy documentation of surgical success (absence of sperm in ejaculate). c Sexual abstinence is considered to be a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of the study and if it is the preferred and usual lifestyle of the participant. d Progestogen-only hormonal contraception, where inhibition of ovulation is not the primary mode of action (minipill) is not accepted as a highly effective method. e These methods are only considered highly effective and therefore acceptable when used in conjunction with a barrier method (i.e., diaphragm with spermicide, sponge with spermicide, cervical cap with spermicide, condoms, spermicide alone.)
• Willing to forgo other immunomodulatory therapies (investigational or otherwise) for NMDAR encephalitis during the study.
• Participant must have received at least 3 days of methylprednisolone 1000 mg IV or equivalent corticosteroid within 90 days prior to randomization (Day 1). In addition, participants must have received EITHER of the following treatments within 90 days before randomization.
• IVIg, at a dose range between 1.2 and 2 g/kg
• Plasma exchange or plasmapheresis, (defined as 5 to 6 exchanges). NOTE: These treatments may be provided during the screening period but must be completed prior to randomization. Participants who receive methylprednisolone and BOTH IVIg and plasma exchange are not excluded from participating in the trial, however, this treatment course with both IVIg and plasma exchange is not encouraged, and enrollment and randomization should not be delayed in order to complete additional first line treatments.
• Modified Rankin Score of ≥3 at the screening visit, indicating at least moderate disability. The baseline mRS must be confirmed by Site Investigators at screening and confirmed / adjudicated before randomization.
• Ability and willingness to attend study visits and complete the study. \*All inclusion criteria must be met during the screening period, prior to randomization, except where noted. Exclusion Criteria Any of the following excludes an individual from participation in the study:
• Any condition that, in the opinion of the Investigator, would interfere with the evaluation or administration of the IP, interpretation of participant safety or study results, or would make participation in the study an unacceptable risk. This specifically includes recent history (last 5 years) of herpes simplex virus encephalitis or known central nervous system demyelinating disease (e.g., multiple sclerosis).
• Presence of an active or chronic infection that is serious in the opinion of the Investigator.
• History of solid organ or cell-based transplantation.
• Concurrent/previous enrollment in another clinical study involving an investigational treatment within 4 weeks or 5 published half-lives of the investigational treatment, whichever is longer, prior to randomization.
• Lactating or pregnant individuals, or individuals who intend to become pregnant anytime from study enrollment to 12 months following last dose of investigational agent.
• Known history of allergy or reaction to any component of the investigational agent formulation or history of anaphylaxis following any biologic therapy.
• Receipt of the following at any time prior to randomization: a. Alemtuzumab b. Total lymphoid irradiation c. Bone marrow transplant d. T-cell vaccination therapy
• Receipt of any biologic B cell-depleting therapy (e.g., rituximab, ocrelizumab, obinutuzumab, ofatumumab, inebilizumab) in the 6 months prior to screening. Receipt of such a B cell-depleting agent in the period 6-12 months prior to screening is exclusionary unless B cell counts have returned to ≥ age-based LLN by central laboratory. For EU participants, B cell counts at screening will be determined by the laboratories of the participating sites. Receipt of non-depleting B cell-directed therapy (e.g., belimumab), abatacept, or other biologic immunomodulatory agent within 6 months prior screening.
• Treatment at therapeutic doses/durations with any of the following within 3 months prior to randomization a. Natalizumab (Tysabri®) b. Cyclosporine c. Methotrexate d. Mitoxantrone e. Cyclophosphamide\* f. Azathioprine g. Mycophenolate mofetil \*Cyclophosphamide is only permitted as rescue therapy to be administered as outlined in Section 5.4.1 no earlier than the week 6 visit.
• Severe drug allergic history or anaphylaxis to two or more food products or medicines (including known sensitivity to acetaminophen/paracetamol, diphenhydramine (cetirizine in EU) or equivalent antihistamine, and methylprednisolone or equivalent glucocorticoid).
• Known history of a primary immunodeficiency (congenital or acquired) or an underlying condition such as human immunodeficiency virus (HIV) infection or splenectomy that predisposes the participant to infection.
• Active malignancy or history of malignancy that was active within the last 10 years, apart from ovarian or extra-ovarian teratoma (also known as a dermoid cyst) or germ cell tumor, or squamous cell carcinoma of the skin or basal cell carcinoma of the skin, that in the opinion of the Medical Safety Monitor (MSM) would preclude enrollment due to safety concerns. Squamous cell and basal cell carcinomas should be treated with documented success of curative therapy \> 3 months prior to randomization.
• At screening (repeat testing may be conducted to confirm results within the same screening period, prior to randomization), any of the following: a. Total white blood count \<2,500 cells/mm3 (or \< 2.5 × 109/L) b. Total immunoglobulin \< 600 mg/dL (or 6 µmol/L; 400 mg/dL for participants \<18 years)\* c. Absolute neutrophil count \< 1200 cells/μL (or \< 1.2 × 109/L) d. CD4 T lymphocyte count \< 300 cells/µL (or \< 0.3 × 109/L) \*Baseline levels of IgG prior to first line treatments (methylprednisolone, plasmapheresis/plasma exchange) should be used to determine eligibility.
• Active hepatitis B or C established with positive hepatitis B serology (hepatitis B surface antigen and core antigen) and/or positive hepatitis C PCR testing and confirmed by the MSM
• Any live or attenuated vaccine within 4 weeks prior to Day 1 (administration of killed vaccines is acceptable).
• Bacillus of Calmette and Guérin (BCG) vaccine within 1 year of enrollment.
• History of alcohol or drug abuse that, in the opinion of the Investigator, might affect participant safety or compliance with visits or interfere with safety or other study assessments.
• Recurrence of previously treated NMDAR encephalitis within the last 5 years, or suspicion of symptomatic untreated NMDAR encephalitis of greater than 3 months duration at the time of screening.
• Evidence of active tuberculosis\* (TB) or being at high risk for TB based on: a. History of active TB or untreated/incompletely treated latent TB. Participants with a history of active or latent TB who have documentation of completion of treatment according to local guidelines may be enrolled. b. History of recent (≤ 12 weeks of screening) close contact with someone with active TB (close contact is defined as ≥ 4 hours/week OR living in the same household OR in a house where a person with active TB is a frequent visitor). c. Signs or symptoms that could represent active TB by medical history or physical examination. d. Positive, indeterminate, or invalid interferon-gamma release assay test result at screening, unless previously treated for TB. Participants with an indeterminate test result can repeat the test once, but if the repeat test is also indeterminate, the participant is excluded. e. Chest radiograph, chest computed tomography or MRI scan that suggests a possible diagnosis of TB or suggests that a work-up for TB should be considered; all participants must have had lung imaging with an acceptable reading within 6 months prior to consent, or during screening.
• Active, clinically significant (CS) infection at the time of randomization (IP administration may be delayed until recovery, if within 14-day screening window, otherwise participant may be rescreened). Exclusion criteria are applied at time of screening and are applicable throughout the study. * Participants will undergo QuantiFERON®-TB Gold testing or equivalent TB testing during screening as standard of care. A positive result will not exclude patients from participation; thus, enrollment should not be delayed awaiting this result. If positive, an appropriate course of anti-TB treatment will need to be documented. If results are in indeterminate, participants may still be eligible for randomization if history is not suggestive of active / latent TB and a chest x-ray shows no evidence of active or latent TB.
• 1 Additional Eligibility Considerations The following criteria are not necessarily exclusionary but require review from the MSM to determine if a participant should be excluded due to safety concerns:
• At screening (out of range lab values may be reviewed with the MSM to determine whether a potential participant should be excluded for safety reasons; repeat testing may be conducted to confirm results within the same screening period, prior to randomization), any of the following:
• Aspartate transaminase (AST) \> 2.5 × age-based upper limit of normal (ULN)
• Alanine transaminase (ALT) \> 2.5 × age-based ULN
• Total bilirubin \> 1.5 × age-based ULN (unless due to Gilbert's syndrome)
• Platelet count \< 75,000/μL (or \< 75 × 109/L)
• Hemoglobin \< 8 g/dL (or \< 80 g/L or 5 mmol/L)
• History of untreated hepatitis C infection. Participants who are considered cured following antiviral therapy with an HCV load below the limit of detection may be enrolled pending confirmation from the MSM that there are no safety concerns for inclusion.
• Patients with coexistent autoantibodies should not immediately be excluded but should be reviewed with the MSM to determine eligibility.
DRUG: Inebilizumab, DRUG: Placebo
Autoimmune Encephalitis, Encephalitis, Brain and Nervous System
Inebilizumab, NMDAR encephalitis, Autoimmune Encephalitis, Rare Disease
UT Southwestern; Children’s Health
Pathogenesis of Uric Acid Nephrolithiasis: Role of Pioglitazone/Weight Loss
The investigators will randomize overweight and obese iuan patients to Pio (45 mg/day, highest approved dose or placebo), WL (10% of body weight, following the established program used in the Diabetes Prevention Program), or Pio+WL. Participants will be evaluated at baseline and after 24 weeks of intervention while on a fixed metabolic diet to exclude the confounding effects of diet and perspiration. The primary endpoint will be change in upH, and multiple additional endpoints (serum, urine, imaging) will be assessed.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Sudeepa.Bhattacharya@UTSouthwestern.edu
Khashayar Sakhaee
ALL
21 Years to 99 Years old
PHASE4
NCT04370093
STU-2019-0907
Inclusion Criteria:
Idiopathic uric acid nephrolithiasis, with last stone analysis showing that stone has \>90% uric acid in composition Age \>21 years Any gender, race/ethnicity (from weight loss), but weight \<165 Kg (to fit into MR instrument); eGFR\>60ml/min/1.73 m2
Exclusion Criteria:
Bariatric surgery, chronic diarrhea, recurrent UTIs current insulin use use of a thiazolidinedione in past 2 years contraindication to thiazolidinedione use (liver dz, pedal edema, CHF NYHA class III/IV, no contraception) Bladder cancer Use of SGLT2-i, GLP-1 analogs, gemfibrozil, topiramate, rifampin Hba1c \> 8.5% DRUG: Pioglitazone 45 mg, BEHAVIORAL: Weight Loss, OTHER: Pioglitazone + Weight Loss
Nephrolithiasis, Uric Acid
Biomedical Sciences
Parkland Health & Hospital System
Trial of Encapsulated Rapamycin (eRapa) for Bladder Cancer Prevention (eRapa)
eRapa (encapsulated rapamycin) will be investigated for secondary prevention in patients with diagnosed non-muscle invasive bladder cancer (NMIBC) through a phase II double-blind randomized controlled trial of long-term (one year) prevention with eRapa versus placebo. The primary hypothesis is that eRapa decreases the risk of cancer relapse for patients with NMIBC. Secondary hypotheses are that eRapa can improve certain immune parameters and improve cognition and physical function without adversely affecting patient-reported outcomes and quality of life.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yair Lotan
ALL
18 Years and over
PHASE2
NCT04375813
STU-2020-0994
Inclusion Criteria:
* Pathologically (histologically) proven diagnosis of non-muscle invasive (Ta, Tis, or T1) bladder cancer within 90 days prior to enrollment
* Able to give informed consent
* 18 years or older
* Patients must not be taking oral glucocorticoids at the time of registration
* Not have active, uncontrolled infections
* No other prior non-bladder malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years.
* Patients with localized prostate cancer who are being followed by an active survelillance program are also eligible.
* Patients must not be pregnant or nursing, as the use of Intravesical BCG is not recommended during pregnancy. Women/ men of reproductive potential must have agreed to use an effective contraceptive method. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. Examples of effective contraception include hormonal contraception, double barrier method (condom with spermicidal cream, diaphragms with spermicidal cream, or condoms with diaphragms), Intrauterine device, and/or partner vasectomy. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy, or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures. Both male and female patients will be required to disclose contraception method during screening and agree to continue to use that contraception method through the end of their participation in the study.
* Patients must have had all grossly visible papillary tumors removed within 90 days prior to registration or cystoscopy confirming no grossly visible papillary tumors within 90 days prior to registration.
* Patients with T1 disease must have cross-sectional imaging of abdomen/pelvis demonstrating no evidence of nodal involvement or metastatic disease (MRI or CT scan) within 90 days prior to registration. Patients with T1 disease must have re-resection confirming ≤ T1 disease within 90 days prior to registration.
* Patients must no have received prior intravesical BCG
Exclusion Criteria:
* Have muscle-invasive or higher (≥T2) bladder cancer
* Unable to give informed consent
* Age 17 or younger
* Taking oral glucocorticoids at the time of registration
* Another cancer requiring active treatment (except basal cell carcinoma or squamous cell carcinoma of the skin)
* Patients at risk of pregnancy that are unwilling or unable to take effective contraception during the study period, or patients that are nursing during the study period. Women/ Men of reproductive potential must have agreed to use an effective contraceptive method or will be considered ineligible for study participation.
* Evidence of nodal involvement or metastatic disease (MRI or CT scan) within 90 days prior to registration
* History of prior intravesical BCG
* History of prior Rapamycin treatment DRUG: eRapa, DRUG: Placebos
Non-muscle Invasive Bladder Cancer, Urinary Bladder
UT Southwestern
Post-Surgical Stereotactic Radiotherapy (SRT) Versus GammaTile-ROADS (Radiation One and Done Study)
This trial will be a randomized controlled study comparing the efficacy and safety of intraoperative radiation therapy using GammaTilesTM (GT) versus SRT 3-4 weeks following metastatic tumor resection which is the current standard of care.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Toral Patel
ALL
18 Years and over
PHASE3
NCT04365374
STU-2020-1338
Inclusion Criteria:
• Patients aged 18 years old and above. Eligibility is restricted to this age group given that the battery of neurocognitive tests utilized in this protocol are not developed or validated for use in a younger population.
• One to six newly diagnosed brain metastases, identified on the screening MRI, from an extracranial primary tumor.
• Only one lesion, designated the index lesion, is planned for surgical resection. The index lesion must be between 2.0 and 7.0 cm in maximal extent on the screening MRI, and gross total resection is expected by the neurosurgeon.
• Non-index lesions must measure ≤ 4.0 cm in maximal extent on the screening MRI brain scan. The unresected lesions will be treated with SRT as outlined in the treatment section of the concept.
• All metastases must be located ≥ 5 mm from the optic chiasm and outside the brainstem. Dural based metastasis are eligible.
• Previous and/or concurrent treatment with investigational or FDA approved systemic therapies (e.g., chemotherapy, targeted therapeutics, immunotherapy) are permitted and must follow protocol guidelines as follows: Systemic therapy is allowed a minimum of one week from last systemic therapy cycle to surgical resection, and one week after surgical resection to allow a minimum of one week before starting/resuming systemic therapy, depending on the specific systemic agent(s), as recommended by medical/neuro-oncology. Systemic therapy is not allowed 1 day before SRT, the same day as the SRT, or 1 day after the completion of the SRT or longer, depending on the specific systemic agent(s), as recommended by medical/neuro-oncology. Agents that are delivered by implant or depot injections (such as hormonal therapies) are excluded from these restrictions.
• Karnofsky Performance Scale (KPS) score of ≥ 70. Patients with KPS \< 70 can be enrolled if their baseline KPS within 14 days of screening was estimated ≥ 70 and surgical management is expected to improve KPS to ≥ 70.
• Stable systemic disease or reasonable systemic treatment options predicting a life expectancy of ≥6 months.
• Ability to complete an MRI of the head with contrast
• Adequate renal and hepatic function to undergo surgery, in investigators opinion.
• For women of childbearing potential only, a negative urine or serum pregnancy test done \<7 days prior to randomization is required. Women must be willing to notify investigator immediately if they become pregnant at any time during the trial period.
• Men and women of childbearing potential must be willing to employ adequate contraception throughout the study and for men for up to 3 months after completing treatment.
• Subjects must be fluent in English, Spanish, or another language the study site is prepared to obtain informed consent for in this trial. English speaking subjects will complete Neurocognitive assessments. Non-English-speaking subjects are trial-eligible but will not complete the Neurocognitive assessments as the psychometric properties for translated tests are either not known or not as robust.
• Willingness and ability to provide written informed consent and HIPAA authorization prior to performance of any study-related procedures. A legally authorized representative may provide consent if the potential subject lacks the capacity to provide consent themselves. Exclusion Criteria
• Age \<18 years.
• Karnofsky Performance Scale (KPS) score of \<70. Patients with KPS \< 70 can be enrolled if their baseline KPS within 14 days of screening was estimated ≥ 70 and surgical management is expected to improve KPS to ≥ 70.
• Sensitivity to bovine (cow) derived materials including collagen products.
• Past radiation or surgical therapy to the index lesion or the newly diagnosed non-index lesion(s) is exclusionary. However, up to a total of 2 prior courses of SRT treatment to previously diagnosed lesions are allowed as long as any treated lesions are were ≥15mm from the index lesion.
• Patients with \>6 newly diagnosed metastases on screening MRI
• Pregnant patients.
• Primary germ cell tumor, small cell carcinoma, or lymphoma.
• Leptomeningeal metastasis (LMD). Note: For the purposes of exclusion, LMD is a clinical diagnosis, defined as radiologic or clinical evidence of leptomeningeal involvement with or without positive cerebrospinal fluid (CSF) cytology.
• Prior WBRT for brain metastases.
• Concomitant therapy that, in the investigator's opinion, would interfere with the evaluation of the safety or efficacy of the study device.
• Comorbid psychiatric or neurologic disease or injury impacting cognition, in the opinion of the treating physician, that might impair patient's ability to understand or comply with the requirements of the study or to provide consent
• Subjects who, in the investigator's opinion, are unable to understand the protocol or to give informed consent, have a history of poor cooperation, noncompliance with medical treatment, or difficulty in returning for follow up care. A legally authorized representative may provide consent if the potential subject lacks the capacity to provide consent themselves.
DEVICE: Gamma Tile-Surgically Targeted Radiation Therapy (STaRT), RADIATION: Stereotactic Radiation Therapy
Brain Metastases, Brain and Nervous System
Brain, Tumor, Cancer, New Diagnosis, Metastases, GammaTile, Radiation, Cs-131
UT Southwestern
Testing the Use of the Usual Chemotherapy Before and After Surgery for Removable Pancreatic Cancer
This phase III trial compares perioperative chemotherapy (given before and after surgery) versus adjuvant chemotherapy (given after surgery) for the treatment of pancreatic cancer that can be removed by surgery (removable/resectable). Chemotherapy drugs, such as fluorouracil, irinotecan, leucovorin, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before and after surgery (perioperatively) may work better in treating patients with pancreatic cancer compared to giving chemotherapy after surgery (adjuvantly).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Patricio Polanco
ALL
18 Years and over
PHASE3
NCT04340141
STU-2020-0951
Inclusion Criteria:
PRE-REGISTRATION:
* Pathology: Histologic or cytologic proof of pancreatic adenocarcinoma or adenosquamous carcinoma
* TNM Stage: Tx-4, N0-1, M0 (M0 disease does not include spread to distant lymph nodes and organs)
* Resectable Primary Tumor: Local radiographic reading must be consistent with resectable disease defined as the following on 1) arterial and venous phase contrast-enhanced abdominal/pelvic CT scan or abdominal/pelvic magnetic resonance imaging (MRI) scan and 2) chest CT:
* No involvement or abutment of the celiac artery, common hepatic artery, superior mesenteric artery, or replaced right hepatic artery (if applicable)
* Less than 180 degree interface between tumor and vessel wall of the portal vein or superior mesenteric vein, and patent portal vein/splenic vein confluence
* No evidence of metastatic disease
* Measurable disease or non-measurable disease o Non-measurable disease is defined as cytologic or histologic confirmation of adenocarcinoma of adenosquamous carcinoma by fine needle aspiration or core-biopsy of the pancreas without measurable disease by radiographic imaging
REGISTRATION:
* Confirmation of resectable disease by real-time central imaging review by the Alliance Imaging Core Lab at Imaging and Radiation Oncology Core (IROC) Ohio
* Determined to be appropriate candidate for curative-intent pancreatectomy by surgeon intending to perform the resection
* No prior radiation therapy, chemotherapy, targeted therapy, investigational therapy, or surgery for pancreatic cancer
* Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects.
* Therefore, for women of childbearing potential only, a negative pregnancy test done =\< 14 days prior to registration is required
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Total Neuropathy Score \< 2
* Absolute neutrophil count (ANC) \>= 1,500/uL
* Platelet count \>= 100,000/uL
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) (If obstructive jaundice is present, then biliary drainage must be initiated and total bilirubin =\< 3.0)
* Creatinine =\< 1.5 x ULN OR calculated (Calc.) creatinine clearance \>= 30 mL/min (Calculated using the Cockcroft-Gault equation)
* No known Gilbert's Syndrome or known homozygosity for UGAT1A1\*28 polymorphism
* No comorbid conditions that would prohibit curative-intent pancreatectomy
* Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug prior to registration
* Chronic concomitant treatment with strong inducers of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inducers must discontinue the drug prior to registration DRUG: Oxaliplatin, DRUG: Irinotecan Hydrochloride, DRUG: Leucovorin Calcium, DRUG: Fluorouracil, PROCEDURE: Resection, OTHER: Questionnaire Administration
Pancreatic Adenosquamous Carcinoma, Resectable Pancreatic Adenocarcinoma, Pancreatic Cancer, Pancreas
UT Southwestern
Study Of Oral Elagolix Tablets In Combination With Combined Oral Contraceptive Capsules/Tablets To Assess Dysmenorrhea Response In Adult Female Participants With Endometriosis And Associated Moderate To Severe Pain (ELARIS EM-COC)
Endometriosis is a painful disorder of the uterus affecting 6-10% of women of childbearing age. Endometriosis affects daily activities, social relationships, sexuality and sexual activity, and mental health. This study will evaluate how well elagolix in combination with combined oral contraceptives (COC) works within the body and/or how safe it is compared to placebo (does not contain treatment drug). This study will assess the dysmenorrhea (painful periods) response in participants with endometriosis and associated pain. Elagolix is an approved drug for the management of moderate to severe pain associated with endometriosis. Participants are randomly put in 1 of 3 groups, called treatment arms. Each group receives a different treatment. There is a 1 in 3 chance that participants will be assigned to placebo. Adult female participants who still have periods with a diagnosis of endometriosis will be enrolled. Around 800 participants will be enrolled in the study at multiple sites in the United States, including Puerto Rico. Participants will receive oral elagolix or placebo tablets in combination with combined oral contraceptive (COC) or placebo capsules for 3 months. All the participants will receive elagolix tablets in combination with COC tablets from Month 4 through Month 18. There will be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the course of the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
studyfinder@utsouthwestern.edu
FEMALE
18 Years to 49 Years old
PHASE3
NCT04333576
Inclusion Criteria:
* Documented surgical confirmation of endometriosis and associated moderate to severe pain.
* Participants must agree to use dual non-hormonal methods of contraception consistently during washout (if applicable), screening, and 3-month double-blind placebo-controlled treatment periods of the study.
* Participant, in the investigator's opinion must be an appropriate candidate to receive combined oral contraceptives (COCs).
Exclusion Criteria:
* Pregnant or breastfeeding or planning a pregnancy until completion of the study.
* Surgical history of hysterectomy or bilateral oophorectomy.
* Participant has osteoporosis or other metabolic bone disease or clinically significant gynecological findings from Screening.
* Participant has any other active chronic pain condition that would interfere with their assessment of endometriosis-related pain. DRUG: Elagolix, DRUG: Placebo, DRUG: Combined Oral Contraceptive
Endometriosis
Endometriosis, Elagolix, Combined oral contraceptives (COC), Orilissa, Dysmenorrhea
A Study of Combination Chemotherapy for Patients With Newly Diagnosed DAWT and Relapsed FHWT
This phase II trial studies how well combination chemotherapy works in treating patients with newly diagnosed stage II-IV diffuse anaplastic Wilms tumors (DAWT) or favorable histology Wilms tumors (FHWT) that have come back (relapsed). Drugs used in chemotherapy regimens such as UH-3 (vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan) and ICE/Cyclo/Topo (ifosfamide, carboplatin, etoposide, cyclophosphamide, and topotecan) work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial may help doctors find out what effects, good and/or bad, regimen UH-3 has on patients with newly diagnosed DAWT and standard risk relapsed FHWT (those treated with only 2 drugs for the initial WT) and regimen ICE/Cyclo/Topo has on patients with high and very high risk relapsed FHWT (those treated with 3 or more drugs for the initial WT).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Jonathan Wickiser
ALL
up to 30 Years old
PHASE2
NCT04322318
STU-2020-1103
Inclusion Criteria:
* Patients with newly diagnosed stages 2 - 4 diffuse anaplastic Wilms tumor must be enrolled on APEC14B1, consented to Part A - Eligibility Screening, and have received an initial stratum assignment showing DAWT (if anaplasia first identified at diagnostic, pre-treatment nephrectomy or biopsy) or a final stratum assignment showing DAWT (if anaplasia first noted at delayed nephrectomy) prior to enrollment on AREN1921. Prior enrollment on APEC14B1 is not an eligibility requirement for patients with relapsed favorable histology Wilms tumor.
* Patients must be =\< 30 years old at study enrollment
* Patients with the following diagnoses are eligible for this study:
* Newly diagnosed stages 2 - 4 diffuse anaplastic Wilms tumor as confirmed by central review
* Favorable histology Wilms tumor at first relapse. Relapsed FHWT patients must have previously achieved remission for their initial FHWT diagnosis to be eligible for this study. The relapse risk groups are defined as follows, regardless of radiation therapy:
* Standard-Risk relapse: Patients who received two chemotherapy agents for frontline therapy; primarily actinomycin D and vincristine
* High-Risk relapse: Patients who received three chemotherapy agents for frontline therapy; primarily vincristine, actinomycin D and doxorubicin or vincristine, actinomycin D and irinotecan
* Very High-Risk relapse: Patients who received four or more chemotherapy agents as part of initial therapy; primarily regimen M or its variations
* Patients with newly diagnosed DAWT must have had histologic verification of the malignancy. For relapsed FHWT patients, biopsy to prove recurrence is encouraged, but not required
* Note: For relapsed FHWT patients, an institutional pathology report confirming favorable histology Wilms tumor (from relapse, if available, or from original diagnosis) must be available for upload prior to initiation of protocol therapy
* Patients with newly diagnosed Stages 2 - 4 diffuse anaplastic Wilms tumor must be enrolled on AREN1921 within 2 weeks of the tumor-directed surgery or biopsy procedure that first confirms a diagnosis of DAWT, whether at initial diagnostic procedure or delayed nephrectomy (such surgery/biopsy is day 0). For patients who received prior therapy for presumed favorable histology Wilms tumor, later confirmed to have diffuse anaplastic Wilms tumor at subsequent review of the initial biopsy
* Patients with newly diagnosed DAWT who undergo upfront nephrectomy must have at least 1 lymph node sampled prior to study enrollment
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* Patients must have a life expectancy of \>= 8 weeks
* Diffuse Anaplastic Wilms Tumor: Patients with diffuse anaplastic histology must have had no prior systemic therapy, except in the following situations:
* Patients with diffuse anaplastic Wilms tumor who received no more than 12 weeks of pre nephrectomy chemotherapy for what was originally presumed to be favorable histology Wilms tumor, subsequently confirmed to be diffuse anaplastic Wilms tumor at delayed nephrectomy
* Patients with diffuse anaplastic Wilms tumor who received no more than 6 weeks of chemotherapy following upfront biopsy, initiated within 14 days of biopsy, for presumed favorable histology Wilms tumor based on institutional review, but subsequently corrected to diffuse anaplastic Wilms tumor based on the initial stratum assignment on APEC14B1-REN
* Treatment consisting of vincristine/doxorubicin/cyclophosphamide initiated on an emergent basis and within allowed timing as described
* Note: Patients who received prior therapy for presumed favorable histology Wilms tumor, later identified to have diffuse anaplastic Wilms tumor as per above, must begin study treatment starting at cycle 3 (week 7) of regimen UH 3. Patients who received emergency radiation to preserve organ function are eligible as noted. Patients who received radiation as part of standard of care for presumed newly diagnosed favorable histology Wilms tumor, along with chemotherapy as noted above, prior to identification of diffuse anaplasia, are also eligible
* Relapsed Favorable Histology Wilms Tumor: Patients must not have received prior chemotherapy for their relapsed favorable histology Wilms tumor diagnosis. In addition, patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
* Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this study
* Radiation therapy (RT): \>= 2 weeks (wks) must have elapsed for local palliative RT (small port); \>= 6 months must have elapsed if prior craniospinal RT or if \>= 50% radiation of pelvis; \>= 6 wks must have elapsed if other substantial bone marrow (BM) radiation. Patients with relapsed favorable histology Wilms tumor who received emergency radiation to preserve organ function are eligible and do not need to washout with the above criteria
* Patients may not be receiving any other investigational agents (within 4 weeks prior to study enrollment)
* Peripheral absolute neutrophil count (ANC) \>= 750/uL (performed within 7 days prior to enrollment)
* Platelet count \>= 75,000/uL (transfusion independent) (performed within 7 days prior to enrollment)
* Hemoglobin \>= 8.0 g/dL (may receive red blood cell \[RBC\] transfusions) (performed within 7 days prior to enrollment)
* Patients with high-risk or very high-risk relapsed FHWT who will be treated with regimen ICE/Cyclo/Topo, must have renal function assessed by creatinine clearance or radioisotope glomerular filtration rate (GFR) and meet the following requirement:
* Creatinine clearance or radioisotope GFR \>= 60 mL/min/1.73 m\^2 (performed within 7 days prior to enrollment)
* Patients diagnosed with stage 2-4 DAWT or standard risk relapsed FHWT, who will be treated with regimen UH 3, may either obtain a creatinine clearance, radioisotope GFR (meeting the above criteria of GFR \>= 60 mL/min/1.73 m\^2), or an adequate serum creatinine as per the following table:
* Age: Maximum Serum Creatinine (mg/dL)
* 1 month to \< 6 months: 0.4 (male and female)
* 6 months to \< 1 year: 0.5 (male and female)
* 1 to \< 2 years: 0.6 (male and female)
* 2 to \< 6 years: 0.8 (male and female)
* 6 to \< 10 years: 1 (male and female)
* 10 to \< 13 years: 1.2 (male and female)
* 13 to \< 16 years: 1.5 (male), 1.4 (female)
* \>= 16 years: 1.7 (male), 1.4 (female)
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age or direct bilirubin =\< ULN for patients whose total bilirubin \> 1.5 x ULN (performed within 7 days prior to enrollment)
* Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 2.5 x upper limit of normal (ULN) for age or =\< 5 x ULN for patients with liver metastases (performed within 7 days prior to enrollment)
* Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \>= 50% by radionuclide angiogram (obtained within 21 days prior to enrollment and start of protocol therapy)
Exclusion Criteria:
* Patients with a history of bilateral Wilms tumor (synchronous or metachronous)
* Patients with any uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, or symptomatic congestive heart failure (defined as grade 2 or higher heart failure per Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0)
* Relapsed FHWT patients who did not receive frontline chemotherapy (e.g., very low risk FHWT initially observed without chemotherapy) or received only one chemotherapy agent for frontline therapy
* For patients with high-risk or very high-risk relapsed FHWT:
* Patients with renal tubular acidosis (RTA) as evidenced by serum bicarbonate \< 16 mmol/L and serum phosphate =\< 2 mg/dL (or \< 0.8 mmol/L) without supplementation
* For stages 2-4 DAWT and standard-risk relapsed FHWT patients:
* Chronic inflammatory bowel disease and/or bowel obstruction
* Concomitant use of St. John's wort, which cannot be stopped prior to the start of trial treatment
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, DRUG: Carboplatin, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, DRUG: Doxorubicin, DRUG: Etoposide, DRUG: Ifosfamide, DRUG: Irinotecan, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, RADIATION: Radiation Therapy, PROCEDURE: Surgical Procedure, DRUG: Topotecan, PROCEDURE: Transabdominal Ultrasound, DRUG: Vincristine, PROCEDURE: X-Ray Imaging
Anaplastic Kidney Wilms Tumor, Recurrent Kidney Wilms Tumor, Stage II Kidney Wilms Tumor, Stage III Kidney Wilms Tumor, Stage IV Kidney Wilms Tumor, Kidney
Children’s Health
Eflornithine (DFMO) and Etoposide for Relapsed/Refractory Neuroblastoma
Difluoromethylornithine (DFMO) will be used in an open label, multicenter, study in combination with etoposide for subjects with relapsed/refractory neuroblastoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tanya Watt
ALL
up to 31 Years old
PHASE2
NCT04301843
STU-2020-1293
Inclusion Criteria:
* All patients must have a pathologically confirmed diagnosis of neuroblastoma, ≤ 30.99 years of age with history of relapsed/refractory neuroblastoma.
* All patients must have completed upfront therapy with at least 4 cycles of aggressive multi-drug chemotherapy.
* Specific Criteria by Arm:
Arms 1 and 2:
Subjects with no active disease:
i. No evidence of residual disease by CT/MRI and MIBG scan (or PET for patients who have a history of MIBG non-avid disease).
o Note: Patients with residual masses detected by CT/MRI may be considered in CR if their MIBG is negative or if MIBG positive and evaluated by PET and found to have negative PET scans; biopsy confirmation may be considered if there is still reasonable concern for persistent disease but is not required.
ii. No evidence of disease metastatic to bone marrow.
Arm 3:
Measurable or evaluable disease, including at least one of the following:
Measurable tumor by CT or MRI; or a positive MIBG and PET; or positive bone marrow biopsy/aspirate in at least one site.
* Timing from prior therapy: Enrollment (first dose of DFMO) no later than 60 days from last dose of the most recent therapy.
* Subjects must have fully recovered from the acute toxic effects of all prior anti- cancer chemotherapy and be within the following timelines:
• Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study (6 weeks if prior nitrosourea).
• Hematopoietic growth factors: At least 5 days since the completion of therapy with a growth factor.
• Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the Study Chair.
• Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines, CAR-T cells.
• Anti-GD2 Monoclonal antibodies: At least 2 weeks must have elapsed since prior treatment with a monoclonal antibody.
• XRT: At least 14 days since the last treatment except for radiation delivered with palliative intent to a non-target site.
• Stem Cell Transplant:
• Allogeneic: No evidence of active graft vs. host disease
• Allo/Auto: ≥ 2 months must have elapsed since transplant.
• MIBG Therapy: At least 8 weeks since treatment with MIBG therapy * Subjects must have a Lansky or Karnofsky Performance Scale score of 60% or higher. * Life expectancy \> 2 months * All clinical and laboratory studies for organ functions to determine eligibility must be performed within 7 days prior to first dose of study drug unless otherwise indicated below. * Subjects must have adequate organ functions at the time of registration: * Hematological: Total absolute neutrophil count ANC ≥750/μL * Liver: Subjects must have adequate liver function as defined by AST and ALT \<5x upper limit of normal (Normal=45), Bilirubin \<1.5x upper limit normal (Normal=1.0). Normal PT, PTT, fibrinogen. * Renal: Adequate renal function defined as (perform one of the following): Creatinine clearance or radioisotope GFR 70 mL/min/1.73 m2 or greater or a serum creatinine based on age/gender * Females of childbearing potential must have a negative pregnancy test. Patients of childbearing potential must agree to use an effective birth control method. Female patients who are lactating must agree to stop breast-feeding. * Written informed consent in accordance with institutional and FDA guidelines must be obtained from all subjects (or patients' legal representative).
Exclusion Criteria:
* BSA of \<0.25 m2.
* Subjects that received DFMO at a dose higher than 1000mg/m2 BID prior to this study are not eligible.
* Subjects that received a dose of DFMO in combination with etoposide are not eligible.
* Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.
* Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from hematological and bone marrow suppression effects of prior chemotherapy.
* Infection: Subjects who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.
* Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded. DRUG: Eflornithine
Neuroblastoma, Brain and Nervous System
Children’s Health
A Study to Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib for Patients With Newly Diagnosed AML With or Without FLT3 Mutations
This phase III trial compares standard chemotherapy to therapy with liposome-encapsulated daunorubicin-cytarabine (CPX-351) and/or gilteritinib for patients with newly diagnosed acute myeloid leukemia with or without FLT3 mutations. Drugs used in chemotherapy, such as daunorubicin, cytarabine, and gemtuzumab ozogamicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. CPX-351 is made up of daunorubicin and cytarabine and is made in a way that makes the drugs stay in the bone marrow longer and could be less likely to cause heart problems than traditional anthracycline drugs, a common class of chemotherapy drug. Some acute myeloid leukemia patients have an abnormality in the structure of a gene called FLT3. Genes are pieces of DNA (molecules that carry instructions for development, functioning, growth and reproduction) inside each cell that tell the cell what to do and when to grow and divide. FLT3 plays an important role in the normal making of blood cells. This gene can have permanent changes that cause it to function abnormally by making cancer cells grow. Gilteritinib may block the abnormal function of the FLT3 gene that makes cancer cells grow. The overall goals of this study are, 1) to compare the effects, good and/or bad, of CPX-351 with daunorubicin and cytarabine on people with newly diagnosed AML to find out which is better, 2) to study the effects, good and/or bad, of adding gilteritinib to AML therapy for patients with high amounts of FLT3/ITD or other FLT3 mutations and 3) to study changes in heart function during and after treatment for AML. Giving CPX-351 and/or gilteritinib with standard chemotherapy may work better in treating patients with acute myeloid leukemia compared to standard chemotherapy alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
ALL
up to 21 Years old
PHASE3
NCT04293562
STU-2020-0830
Inclusion Criteria:
* All patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to enrollment and treatment on AAML1831
* Patients must be less than 22 years of age at the time of study enrollment
* Patient must be newly diagnosed with de novo AML according to the 2016 World Health Organization (WHO) classification with or without extramedullary disease
* Patient must have 1 of the following:
* \>= 20% bone marrow blasts (obtained within 14 days prior to enrollment)
* In cases where extensive fibrosis may result in a dry tap, blast count can be obtained from touch imprints or estimated from an adequate bone marrow core biopsy
* \< 20% bone marrow blasts with one or more of the genetic abnormalities associated with childhood/young adult AML as provided in the protocol (sample obtained within 14 days prior to enrollment)
* A complete blood count (CBC) documenting the presence of at least 1,000/uL (i.e., a white blood cell \[WBC\] count \>= 10,000/uL with \>= 10% blasts or a WBC count of \>= 5,000/uL with \>= 20% blasts) circulating leukemic cells (blasts) if a bone marrow aspirate or biopsy cannot be performed (performed within 7 days prior to enrollment)
* ARM C: Patient must be \>= 2 years of age at the time of Late Callback
* ARM C: Patient must have FLT3/ITD allelic ratio \> 0.1 as reported by Molecular Oncology
* ARM C: Patient does not have any congenital long QT syndrome or congenital heart block
* ARM C: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib
* ARM C: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib
* ARM C: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib
* ARM D: Patient must be \>= 2 years of age at the time of Late Callback
* ARM D: Patient must have one of the clinically relevant non-ITD FLT3 activating mutations as reported by Foundation Medicine
* ARM D: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib
* ARM D: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib
* ARM D: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib
* NEUROPSYCHOLOGICAL TESTING: Patient must be enrolled on Arm A or Arm B. Patients who transfer to Arm C or Arm D are not eligible
* NEUROPSYCHOLOGICAL TESTING: Patient must be 5 years or older at the time of enrollment
* NEUROPSYCHOLOGICAL TESTING: English-, French- or Spanish-speaking
* NEUROPSYCHOLOGICAL TESTING: No known history of neurodevelopmental disorder prior to diagnosis of AML (e.g., Down syndrome, fragile X, William syndrome, mental retardation)
* NEUROPSYCHOLOGICAL TESTING: No significant visual or motor impairment that would prevent computer use or recognition of visual test stimuli
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
* Fanconi anemia
* Shwachman Diamond syndrome
* Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21
* Telomere disorders
* Germline predispositions known, or suspected by the treating physician to increase risk of toxicity with AML therapy
* Any concurrent malignancy
* Juvenile myelomonocytic leukemia (JMML)
* Philadelphia chromosome positive AML
* Mixed phenotype acute leukemia
* Acute promyelocytic leukemia
* Acute myeloid leukemia arising from myelodysplasia
* Therapy-related myeloid neoplasms
* Patients with persistent cardiac dysfunction prior to enrollment, defined as ejection fraction (EF) \< 50% (preferred method Biplane Simpson's EF) or if EF unavailable, shortening fraction (SF) \< 24%. \*Note: if clinically safe and feasible, repeat echocardiogram is strongly advised in order to confirm cardiac dysfunction following clinical stabilization, particularly if occurring in the setting of sepsis or other transient physiologic stressor. If the repeat echocardiogram demonstrates an EF \>= 50%, the patient is eligible to enroll and may receive an anthracycline-containing Induction regimen
* Administration of prior anti-cancer therapy except as outlined below:
* Hydroxyurea
* All-trans retinoic acid (ATRA)
* Corticosteroids (any route)
* Intrathecal therapy given at diagnosis
* In particular, strong inducers of CYP3A4 and/or P-glycoprotein (P-gp) should be avoided from the time of enrollment until it is determined whether the patient will receive gilteritinib. Patients receiving gilteritinib will be required to avoid strong CYP3A4 inducers and/or strong P-gp inducers for the duration of the study treatment
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
* ARM D: Patient does not have any congenital long QT syndrome or congenital heart block PROCEDURE: Allogeneic Hematopoietic Stem Cell Transplantation, DRUG: Asparaginase Erwinia chrysanthemi, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Computed Tomography, DRUG: Cytarabine, DRUG: Daunorubicin Hydrochloride, DRUG: Dexrazoxane Hydrochloride, DRUG: Etoposide, OTHER: Fludeoxyglucose F-18, DRUG: Gemtuzumab Ozogamicin, DRUG: Gilteritinib Fumarate, DRUG: Liposome-encapsulated Daunorubicin-Cytarabine, PROCEDURE: Magnetic Resonance Imaging, DRUG: Methotrexate, DRUG: Mitoxantrone Hydrochloride, PROCEDURE: Positron Emission Tomography, OTHER: Questionnaire Administration, DRUG: Therapeutic Hydrocortisone
Acute Myeloid Leukemia, Myeloid and Monocytic Leukemia
Children’s Health
Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children Per Standard of Care (POPS) (POPS or POP02)
The study investigators are interested in learning more about how drugs, that are given to children by their health care provider, act in the bodies of children and young adults in hopes to find the most safe and effective dose for children. The primary objective of this study is to evaluate the PK of understudied drugs currently being administered to children per SOC as prescribed by their treating provider.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Aruna.Ayalasomayajula@UTSouthwestern.edu
Mia Maamari
ALL
0 Years to 20 Years old
NCT04278404
STU-2021-0176
Inclusion Criteria:
• Participant is \< 21 years of age
• Parent/ Legal Guardian/ Adult Participant can understand the consent process and is willing to provide informed consent/HIPAA:
• (a) Participant is receiving one or more of the study drugs of interest at the time of enrollment or (b) Participant is NOT receiving one or more of the study drugs of interest but is SARS-COV-2 positive within 60 days prior to enrollment
Exclusion Criteria:
• Participant has a known pregnancy Below exclusion criteria apply only to: Participants receiving one or more of the study drugs of interest at the time of enrollment, DOI administration or PK sampling: (Refer to DOI specific appendices for details on enrollment cohort specifications and additional eligibility criteria)
• Has had intermittent dialysis within previous 24 hours
• Has had a kidney transplant within previous 30 days
• Has had a liver transplant within previous 1 year
• Has had a stem cell transplant within previous 1 year
• Has had therapeutic hypothermia within previous 24 hours
• Has had plasmapheresis within the previous 24 hours
• Has a Ventricular Assist Device
• Has any condition which would make the participant, in the opinion of the investigator, unsuitable for the study
DRUG: The POP02 study is collecting bodily fluid samples (i.e., whole blood, effluent samples) of children prescribed the following drugs of interest per standard of care:
Coronavirus Infection (COVID-19), Pulmonary Arterial Hypertension, Urinary Tract Infections in Children, Hypertension, Pain, Hyperphosphatemia, Primary Hyperaldosteronism, Edema, Hypokalemia, Heart Failure, Hemophilia, Menorrhagia, Insomnia, Pneumonia, Skin Infection, Arrythmia, Asthma in Children, Bronchopulmonary Dysplasia, Adrenal Insufficiency, Fibrinolysis, Hemorrhage, Attention Deficit Hyperactivity Disorder, Multisystem Inflammatory Syndrome in Children (MIS-C), Kawasaki Disease, Coagulation Disorder, Down Syndrome
Children’s Health
Testing Early Treatment for Patients With High-Risk Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL), EVOLVE CLL/SLL Study
This phase III trial compares early treatment with venetoclax and obinutuzumab versus delayed treatment with venetoclax and obinutuzumab in patients with newly diagnosed high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Starting treatment with the venetoclax and obinutuzumab early (before patients have symptoms) may have better outcomes for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma compared to starting treatment with the venetoclax and obinutuzumab after patients show symptoms.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Farrukh Awan
ALL
18 Years and over
PHASE3
NCT04269902
STU-2022-0539
Inclusion Criteria:
* Participants must have a confirmed diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (collectively referred to as CLL throughout) according to the 2018 International Workshop on CLL. Participants must have been diagnosed within 18 months prior to registration
* Participants must have CLL-International Prognostic Index (CLL-IPI) score \>= 4 and/or complex cytogenetics (defined as 3+ chromosomal abnormalities)
* Cytogenetic AND/OR FISH analyses must be completed at a Clinical Laboratory Improvement Act (CLIA)-approved (or laboratories accredited under Accreditation Canada Diagnostics to conduct FISH analyses) laboratory within 18 months prior to registration. At minimum, FISH panel should use probes to detect for abnormalities in chromosomes 13q, 12, 11q, and 17p
* TP53 gene mutation analysis performed at any CLIA-approved (or laboratories accredited under Accreditation Canada Diagnostics) lab (if completed) must be obtained within 18 months prior to registration. This sequencing test is distinct from FISH studies for del(17p)
* Note: TP53 gene mutation analysis is recommended but not required if the participant meets disease-related study criteria via a combination of risk factors that totals a score of 4 on the CLL-IPI score and/or has complex cytogenetics completed
* Immunoglobulin heavy chain locus variable (IgVH) gene mutation analysis performed at any CLIA-approved lab (or laboratories accredited under Accreditation Canada Diagnostics) must be obtained prior to registration (at any time prior to registration)
* Serum beta-2 microglobulin level must be obtained within 28 days prior to registration
* Participants must not meet any of the IWCLL specified criteria for active CLL therapy
* Treatment with high dose corticosteroids and/or intravenous immunoglobulin for autoimmune complications of CLL must be complete at least 4 weeks prior to enrollment
* Steroids used for treatment of conditions other than CLL/SLL must be at a dose of at most 20 mg/day of prednisone or equivalent corticosteroid at the time of registration
* Prior therapy with anti CD20 monoclonal antibodies is not allowed
* Participants must not have received or be currently receiving any prior CLL-directed therapy, including non-protocol-related therapy, anti-cancer immunotherapy, experimental therapy (with exception of agents approved for emergency access use for the prevention or treatment of COVID-19), or radiotherapy
* Participants must not be receiving or planning to receive any other investigational agents before completing protocol therapy
* Participants must be \>= 18 years of age
* Participants must have Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
* Platelet count \>= 100,000/mm\^3 within 28 days prior to registration
* Absolute neutrophil count (ANC) \>= 1,000/mm\^3 within 28 days prior to registration
* Creatinine clearance \>= 30mL/min (by Cockcroft Gault) within 28 days prior to registration
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3.0 x upper limit of normal (ULN) within 28 days prior to registration
* Total bilirubin =\< 2.0 x ULN (or 5.0 x ULN if the participant has a history of Gilbert's disease), within 28 days prior to registration
* Participants must be able to take oral medications
* Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* Participants with history of malignancy are allowed providing the cancer has not required active treatment within 2 years prior to registration (hormonal therapy is permissible). The following exceptions are permissible: basal cell, squamous cell skin, or non-melanomatous skin cancer, in situ cervical cancer, superficial bladder cancer not treated with intravesical chemotherapy or Bacillus Calmette-Guerin (BCG) within 6 months, localized prostate cancer requiring no more than chronic hormonal therapy, or localized breast cancer requiring no more than chronic hormonal therapy
* Participants must not have current, clinically significant gastrointestinal malabsorption, in the opinion of treating doctor
* Participants must not have cirrhosis
* Obinutuzumab has been associated with hepatitis reactivation. Participants must not have uncontrolled active infection with hepatitis B or C. Participants with latent hepatitis B infection must agree to take prophylaxis during and for 6 months following active protocol therapy with V-O.
* Active infection with hepatitis B or C:
* Active infection is defined as detectable hepatitis B deoxyribonucleic acid (DNA) or hepatitis C ribonucleic acid (RNA) by quantitative polymerase chain reaction (PCR).
* Latent infection with hepatitis B:
* Latent infection is defined as meeting all of the following criteria:
* Hepatitis B surface antigen positive
* Anti-hepatitis B total core antibody positive
* Anti-hepatitis IgM core antibody undetectable
* Hepatitis B PCR undetectable
* Participants with latent hepatitis B infection must agree to take prophylaxis with anti-hepatitis agents during and for 6 months following active protocol therapy with V-O.
* Participants who have received intravenous immunoglobulin (IVIG) therapy within 6 months who are hepatitis B core total antibody positive but PCR undetectable are not mandated to take prophylaxis
* Participants must not have had major surgery within 30 days prior registration or minor surgery within 7 days prior to registration. Examples of major surgery include neurosurgical procedures, joint replacements, and surgeries that occur inside the thoracic or abdomino-pelvic cavities. Examples of minor surgery include dental surgery, insertion of a venous access device, skin biopsy, or aspiration of a joint. If a participant has had a bone marrow biopsy for diagnosis or evaluation of CLL, this will not exclude the participant from registration to the study. If there is a question about whether a surgery is major or minor, this should be discussed with the Study Chair
* Participants must not have known bleeding disorders (e.g., von Willebrand's disease or hemophilia)
* Participants must not have a history of stroke or intracranial hemorrhage within 6 months prior to enrollment
* Participants must not require continued therapy with a strong inhibitor or inducer of CYP3A4/5, as venetoclax is extensively metabolized by CYP3A4/5
* Participants must not have uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura
* Participants must not have any currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification
* Participants must not have a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to enrollment
* Participants must not be pregnant or nursing, as there are no safety data available for these drug regimens during pregnancy. Women/men of reproductive potential must have agreed to use an effective contraceptive method. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
* Participants must agree to have specimens submitted for translational medicine (MRD) as outlined
* Participants must be offered the opportunity to participate in specimen banking for future research as outlined.
* NOTE: With participant's consent, the site must follow through with specimen submission as outlined
* Participants who are able to complete patient reported outcome (PRO) forms in English, Spanish, French, German, Russian or Mandarin must agree to participate in the quality of life assessments. (Those participants who are unable to read and write in English, Spanish, French, German, Russian or Mandarin may be registered to S1925 without contributing to the quality of life portion of the study.)
* Participants must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
* NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Computed Tomography, BIOLOGICAL: Obinutuzumab, OTHER: Questionnaire Administration, DRUG: Venetoclax
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
UT Southwestern
Testing the Addition of a Type of Drug Called Immunotherapy to the Usual Chemotherapy Treatment for Non-Small Cell Lung Cancer, ALCHEMIST Trial
This phase III ALCHEMIST trial tests the addition of pembrolizumab to usual chemotherapy for the treatment of stage IIA, IIB, IIIA or IIIB non-small cell lung cancer that has been removed by surgery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as cisplatin, pemetrexed, carboplatin, gemcitabine hydrochloride, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab with usual chemotherapy may help increase survival times in patients with stage IIA, IIB, IIIA or IIIB non-small cell lung cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Gerber
ALL
18 Years and over
PHASE3
NCT04267848
STU-2020-0684
Inclusion Criteria:
* A female of childbearing potential is a sexually mature female who:
* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
* Local testing of EGFR with no EGFR exon 19 deletion or EGFR L858 R mutation (applicable to non-squamous patients only)
* Local testing of ALK with no ALK rearrangement (failed testing is considered negative) (applicable to non-squamous patients only)
* Local testing of PD-L1 immunohistochemistry (IHC) using one of the following assays: DAKO 22C3, DAKO 28-8, EIL3N or SP263
* Completely resected stage IIA, IIB IIIA or IIIB (T3-4N2) non-small cell lung cancer (NSCLC) (squamous or non-squamous) with negative margins (complete R0 resection). Patients will be staged according to the 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual, 2017
* Note: Patients with pathologic N2 disease, completely resected, are eligible. However, patients known to have N2 disease prior to surgery are not eligible; guidelines do not recommend up-front surgery for this population
* Complete recovery from surgery. Registration to A081801 must be 30-77 days following surgery
* No prior neoadjuvant or adjuvant therapy for current lung cancer diagnosis
* No prior allogeneic tissue/solid organ transplant
* Patients must NOT have uncontrolled intercurrent illness including, but not limited to, serious ongoing or active infection, symptomatic congestive heart failure, uncontrolled cardiac arrhythmia, unstable angina pectoris, that would limit compliance with study requirements
* No current pneumonitis or history of (non-infectious) pneumonitis that required steroids
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0-1
* No active auto-immune disease that has required systemic treatment within the last 2 years (e.g., disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid release therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment
* Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects
* Therefore, for women of childbearing potential only, a negative pregnancy test done =\< 7 days prior to registration is required
* No patients with a "currently active" second malignancy that is progressing or has required active treatment within the last 3 years. Participants with non-melanoma skin cancers or carcinoma in situ (e.g., breast carcinoma or cervical cancer in situ) that have undergone potentially curative therapy are eligible
* No hypersensitivity (\>= grade 3) to pembrolizumab and/or any of its excipients
* No live vaccine within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
* No known history of hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known hepatitis C virus (defined as HCV ribonucleic acid \[RNA\] \[qualitative\] is detected) infection
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Hemoglobin \>= 8 gm/dl
* Calculated (Calc.) creatinine clearance \>= 45 mL/min
* Total bilirubin =\< 1.5 x upper limit of normal (ULN)
* Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN) PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, DRUG: Cisplatin, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography Test, DRUG: Gemcitabine Hydrochloride, PROCEDURE: Magnetic Resonance Imaging, OTHER: Observation Activity, DRUG: Paclitaxel, BIOLOGICAL: Pembrolizumab, DRUG: Pemetrexed Disodium, OTHER: Questionnaire Administration
Lung Non-Small Cell Carcinoma, Lung Non-Small Cell Squamous Carcinoma, Lung Non-Squamous Non-Small Cell Carcinoma, Stage II Lung Cancer AJCC v8, Stage IIIA Lung Cancer AJCC v8, Stage IIIB Lung Cancer AJCC v8, Lung/Thoracic
UT Southwestern; Parkland Health & Hospital System
Pragmatic Evaluation of Events And Benefits of Lipid-lowering in Older Adults (PREVENTABLE)
PREVENTABLE is a multi-center, randomized, parallel group, placebo-controlled superiority study. Participants will be randomized 1:1 to atorvastatin 40 mg or placebo. This large study conducted in community-dwelling older adults without cardiovascular disease (CVD) or dementia will demonstrate the benefit of statins for reducing the primary composite of death, dementia, and persistent disability and secondary composites including mild cognitive impairment (MCI) and cardiovascular events.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Gentina.Thompson@UTSouthwestern.edu
Craig Rubin
ALL
75 Years and over
PHASE4
NCT04262206
STU-2020-0579
Inclusion Criteria:
* Community-dwelling adults
* Age ≥75 years
* English or Spanish as primary language
* Able to provide a trusted contact
Exclusion Criteria:
* Clinically evident cardiovascular disease defined as prior myocardial Infarction (MI), prior stroke, prior revascularization procedure, or a secondary prevention indication for a statin (clinician determined)
* Hospitalization for a primary diagnosis of heart failure in the prior 12 months (Note: History of heart failure in the absence of recent hospitalization or clinically evident cardiovascular disease is not an exclusion)
* Dementia (clinically evident or previously diagnosed)
* Dependence in any Katz Basic Activities of Daily Living \[ADL\] (with the exception of urinary or bowel continence)
* Severe hearing impairment (preventing phone follow up)
* Unable to talk (preventing phone follow up)
* Statin use in the past year or for longer than 5 years previously (participant reported)
* Ineligible to take atorvastatin 40 mg (clinician determined)
* Documented intolerance to statins
* Active Liver Disease DRUG: Atorvastatin 40 Mg Oral Tablet, DRUG: Placebo oral tablet
Cognitive Impairment, Mild, Dementia, Cardiovascular Diseases, Unknown Sites
statin, older adults
UT Southwestern; Parkland Health & Hospital System
A Study of ASTX030 (Cedazuridine in Combination With Azacitidine) in MDS, CMML, or AML
Study ASTX030-01 is designed to move efficiently from Phase 1 to Phase 3. Phase 1 consists of an open-label Dose Escalation Stage (Stage A) using multiple cohorts at escalating dose levels of oral cedazuridine and azacitidine (only one study drug will be escalated at a time) followed by a Dose Expansion Stage (Stage B). Phase 2 is a randomized, open-label, crossover study to compare oral ASTX030 to subcutaneous (SC) azacitidine. Phase 3 is a randomized open-label crossover study comparing the final oral ASTX030 dose to SC azacitidine. The duration of this phase 1-3 study is approximately 7 years.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years and over
PHASE2
NCT04256317
STU-2023-0235
Inclusion Criteria:
Phase 2:
• Has Confirmed MDS, CMML, MDS/MPN or AML diagnosis who are candidates to receive and benefit from single agent azacitidine and as applicable according to local country approvals and/or local institution standard practice. Phase 3:
• Has confirmed MDS or CMML and is a candidate to receive and benefit from single agent azacitidine as applicable according to local country approvals and/or local institution standard practice: a) French-American-British myelodysplastic syndrome subtypes: refractory anemia (RA) or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and CMML or MDS with intermediate-2 or high risk MDS according to the International Prognostic Scoring System (IPSS).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Participants with adequate organ function.
• For participants with prior allogeneic stem cell transplant, no evidence of graft-versus-host disease (GVHD).
• Participants with no major surgery within 3 weeks before first study treatment.
• Participants with no cytotoxic chemotherapy (excluding hydroxyurea) within 4 weeks before first study treatment.
• Participants with projected life expectancy of at least 12 weeks.
Exclusion Criteria:
Phase 2 and 3:
• Has an active uncontrolled gastric or duodenal ulcer.
• Has poor medical risk because of other conditions.
• Has known human immunodeficiency virus (HIV) infection.
• Is known to be positive for Hepatitis B or C infection.
• Has a life-threatening illness.
• Has a history of other malignancies prior to study entry, with the exception of adequately treated in situ carcinoma of the breast or cervix uteri; localized basal cell carcinoma or squamous cell carcinoma of the skin; previous malignancy confined and surgically resected or adequately treated and controlled with other modalities; and any early stage malignancy for which no definitive therapy is required.
• Participants with MDS/MPN including CMML who have clinical extramedullary disease including clinically palpable hepatomegaly or splenomegaly.
• Has previous treatment with more than 1 cycle of decitabine, azacitidine, or guadecitabine (Phases 2 and 3 only).
• Has been treated with any investigational drug or therapy within 2 weeks, or 5 half-lives, whichever is longer, before the protocol-defined first dose of study treatment, or ongoing clinically significant adverse events from previous treatment with investigational drug or therapy.
• Has a known or suspected hypersensitivity to cedazuridine or azacitidine or any of their excipients.
DRUG: Azacitidine, DRUG: ASTX030 (cedazuridine + azacitidine), DRUG: Azacitidine, DRUG: ASTX030 (cedazuridine + azacitidine), DRUG: Cedazuridine
Myelodysplastic Syndromes, Acute Myeloid Leukemia, Myelodysplastic Syndrome/Neoplasm, Chronic Myelomonocytic Leukemia, Leukemia, Other, Myeloid and Monocytic Leukemia
ASTX030, Myeloid Neoplasm, Hematologic Disease, Leukemia, Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), Chronic Myelomonocytic Leukemia (CMML), Vidaza™, Azacitadine, Azacitadine and cedazuridine drug combination
UT Southwestern
Testing the Addition of Radiotherapy to the Usual Treatment (Chemotherapy) for Patients With Esophageal and Gastric Cancer That Has Spread to a Limited Number of Other Places in the Body
This phase III trial studies how well the addition of radiotherapy to the usual treatment (chemotherapy) works compared to the usual treatment alone in treating patients with esophageal and gastric cancer that has spread to a limited number of other places in the body (oligometastatic disease). Radiotherapy uses high energy x-rays, gamma rays, or protons to kill tumor cells and shrink tumors. Drugs used in usual chemotherapy, such as leucovorin, 5-fluorouracil, oxaliplatin, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding radiotherapy to the usual chemotherapy may work better compared to the usual chemotherapy alone in treating patients with esophageal and gastric cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Nina Sanford
ALL
18 Years and over
PHASE3
NCT04248452
STU-2020-0217
Inclusion Criteria:
* REGISTRATION TO STEP 1
* Patient must have histologically confirmed HER2 negative metastatic esophageal or gastric adenocarcinoma (American Joint Committee on Cancer \[AJCC\] 8th edition)
* Patient must have oligometastatic disease at the time of registration, which is defined as the following:
* At most 3 radiologically visible metastatic lesions (not sites), in addition to the primary site. Computed tomography (CT) or magnetic resonance imaging (MRI) scans will be performed for staging purposes. Patients with oligometastatic sites that are only detected with positron emission tomography (PET)/CT will be eligible for participation, as long as radiation planning and administration is feasible after discussion with treating radiation oncologist. Malignant lymph node should be at least 1 cm in size or biopsy proven involved by disease
* Anatomically defined lymphadenopathy will be considered as 1 site of metastatic disease. For example, 2 enlarged paraaortic lymph nodes will be considered as one site, and 2 additional sites will be allowed to meet protocol definition of oligometastatic disease. However, if supraclavicular or cervical nodes are involved for distal esophageal tumors or gastric tumors, these are counted separately from intrathoracic nodes. For upper thoracic/cervical esophageal tumors, the involvement of celiac nodes are counted separately from intrathoracic nodes. Intrathoracic nodes, defined as hilar and mediastinal nodes, will be collectively counted as one
* Patients with radiologically evident peritoneal metastasis will be excluded.
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Women of childbearing potential and sexually active males must not expect to conceive or father children by using accepted and effective method(s) of contraception (both double barrier contraception and birth control pills or implants) or by abstaining from sexual intercourse for at least one month after the last dose of protocol treatment and continuing for 5 months after the last dose of protocol treatment (for female patients) and for 7 months after the last dose of protocol treatment (for male patients who are sexually active with women of child bearing potential \[WOCBP\]). Investigators must counsel WOCBP and male patients who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (obtained within 28 days prior to registration)
* Hemoglobin \>= 8 g/dL (obtained within 28 days prior to registration)
* Platelets (PLT) \>= 100 x 10\^9/L (obtained within 28 days prior to registration)
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3.0 x upper limit of normal (ULN) (obtained within 28 days prior to registration)
* Bilirubin =\< 1.5 x institutional ULN (obtained within 28 days prior to registration)
* Serum creatinine =\< 1.5 x institutional ULN (Cockcroft and Gault formula) (obtained within 28 days prior to registration)
* Albumin \> 2.5 g/dL (obtained within 28 days prior to registration)
* Patient must be able to understand and willing to sign and date the written voluntary informed consent form prior to any protocol-specific procedures
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Patients must have CD4 \> 200 at the time of registration
* NOTE: HIV testing is not required for eligibility
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients who had prior definitive treatment for early stage EGA with either surgery or chemoradiation are eligible for participation as long as recurrent disease developed at least 6 months after completion of all prior therapies
* Any major surgery must have been completed \>= 4 weeks prior to registration
* REGISTRATION TO STEP 2
* Patient must have histologically confirmed HER2 negative metastatic esophageal or gastric adenocarcinoma (AJCC 8th edition) with stable disease after about 4 months of fluorouracil, leucovorin calcium, and oxaliplatin (FOLFOX) or 6 cycles of capecitabine and oxaliplatin (CAPOX) (Step 1 treatment)
* Patient must have no evidence of disease progression based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria since Step 1 registration. Patients with complete radiologic response are eligible for Step 2
* Patient must have an ECOG performance status 0-1
Exclusion Criteria:
* Patient must not have any contraindications to 5-fluorouracil (5-FU) or capecitabine, oxaliplatin
* Patient must not have any contraindications to radiation therapy based on consultation with a radiation oncologist. Formal radiation oncology evaluation will be required for eligibility purposes. Prior palliative or definitive radiation to the primary site is allowed, as long as it was completed at least 2 weeks before registration
* Women must not be pregnant or breast-feeding due to the potential harm to unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used
* All females of child bearing potential must have a serum or urine pregnancy test to rule out pregnancy within 14 days prior to registration
* A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: has achieved menarche at some point, has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patient must not have had any prior treatment with 5-FU or capecitabine and/or oxaliplatin containing systemic therapy
* NOTE: Patients previously treated with radiosensitizing doses of 5-FU will be eligible for participation as long as adequate time has elapsed from past treatments
* NOTE: Patients who received systemic 5-FU or capecitabine and/or oxaliplatin as part of the treatment for their locoregional disease are eligible for participation, as long as all definitive therapy has been completed at least 6 months prior to trial enrollment
* Patients with known central nervous system (CNS) metastasis will be excluded from trial participation, regardless of the status of the CNS disease
* Patient must not have any uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring treatment, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Patient must not have had live vaccines within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette Guerin (BCG), and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines and are not allowed DRUG: Capecitabine, DRUG: Fluorouracil, DRUG: Leucovorin, DRUG: Leucovorin Calcium, DRUG: Oxaliplatin, RADIATION: Radiation Therapy
Clinical Stage IV Esophageal Adenocarcinoma AJCC v8, Clinical Stage IV Gastric Cancer AJCC v8, Clinical Stage IVA Esophageal Adenocarcinoma AJCC v8, Clinical Stage IVA Gastric Cancer AJCC v8, Clinical Stage IVB Esophageal Adenocarcinoma AJCC v8, Clinical Stage IVB Gastric Cancer AJCC v8, Metastatic Esophageal Adenocarcinoma, Metastatic Gastric Adenocarcinoma, Oligometastatic Esophageal Adenocarcinoma, Oligometastatic Gastric Adenocarcinoma, Pathologic Stage IV Esophageal Adenocarcinoma AJCC v8, Pathologic Stage IV Gastric Cancer AJCC v8, Pathologic Stage IVA Esophageal Adenocarcinoma AJCC v8, Pathologic Stage IVB Esophageal Adenocarcinoma AJCC v8, Esophagus
UT Southwestern
Osimertinib With or Without Bevacizumab as Initial Treatment for Patients With EGFR-Mutant Lung Cancer
This phase III trial compares the effect of bevacizumab and osimertinib combination vs. osimertinib alone for the treatment of non-small cell lung cancer that has spread outside of the lungs (stage IIIB-IV) and has a change (mutation) in a gene called EGFR. The EGFR protein is involved in cell signaling pathways that control cell division and survival. Sometimes, mutations in the EGFR gene cause EGFR proteins to be made in higher than normal amounts on some types of cancer cells. This causes cancer cells to divide more rapidly. Osimertinib may stop the growth of tumor cells by blocking EGFR that is needed for cell growth in this type of cancer. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving osimertinib with bevacizumab may control cancer for longer and help patients live longer as compared to osimertinib alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Sheena Bhalla
ALL
18 Years and over
PHASE3
NCT04181060
STU-2022-0495
Inclusion Criteria:
* Patient must have a pathologically-confirmed diagnosis of non-squamous, non-small cell lung cancer (NSCLC)
* Patient must have advanced disease, defined as - either stage IV disease, stage IIIB disease not amenable to definitive multi-modality therapy, or recurrent disease after a prior diagnosis of stage I-III disease. All staging is via the American Joint Committee on Cancer (AJCC)/International Association for the Study of Lung Cancer (IASLC) 8th edition staging criteria
* Patient must have somatic activating sensitizing mutation in EGFR (e.g. but not limited to Exon 19 deletion, L858R, E709X, G719X, exon 19 insertions, L861Q, S768I). Patients with non-sensitizing mutations in EGFR (EGFR exon 20 insertions) are not eligible. Test results originating from a Clinical Laboratory Improvement Act (CLIA)-certified or similarly accredited laboratory are acceptable; no specific assay is mandated. Plasma, cytology, or tumor tissue can be utilized for mutation testing
* Patient must not have received any prior treatment with an anti-VEGF agent
* NOTE: Prior treatment with an EGFR TKI is not allowed, however if a candidate for this study has already started osimertinib within 21 days prior to randomization, the exact osimertinib start date is known, and the patient had the required study baseline imaging completed prior to the osimertinib start date, the patient will be eligible
* Patients that have received prior radiation therapy are eligible. Radiation (limited field stereotactic radiation or conventional radiation) must have been completed at least one week prior to study drug initiation and more extensive field radiation (i.e., whole-brain radiotherapy \[WBRT\]) must have been completed at least two weeks prior to drug initiation
* Patient must not have any risk factors for anti-VEGF administration, specifically, hemoptysis, active cardiovascular disease, uncontrolled hypertension, significant proteinuria (screening urinalysis \> 300 mg/dl) and tumor invading major blood vessels
* Patient must have measurable disease. Baseline measurements of sites of disease must be obtained within 4 weeks prior to study randomization. If a potential target lesion is previously irradiated without subsequent growth and/or is radiated after the imaging from which baseline measurements are obtained, they cannot be included as target lesions, and additional target lesions are required to meet criteria for measurable disease
* Patient must not have had any prior systemic treatment for metastatic disease
* Patient must be ≥ 18 years of age
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used
* All females of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy
* A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patient of childbearing potential and sexually active males must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for 2 weeks prior to the start of treatment, while on study treatment, and for
* 6 weeks after the last dose of protocol treatment for female patients on the osimertinib (AZD9291) alone arm
* 4 months after the last dose of protocol treatment for male patients on osimertinib (AZD9291) alone arm
* 6 months after the last dose of protocol treatment for all patients on osimertinib (AZD9291) plus bevacizumab combination arm
* NOTE: Female patients should also not breastfeed while on treatment and for 6 months after the last dose bevacizumab
* Leukocytes \>= 3,000/mcL (obtained =\< 14 days prior to randomization)
* Absolute neutrophil count \>= 1,500/mcL (obtained =\< 14 days prior to randomization)
* Platelets \>= 100,000/mcL (obtained =\< 14 days prior to randomization)
* Hemoglobin \>= 9 g/dL (obtained =\< 14 days prior to randomization)
* Total bilirubin and creatinine =\< 1.5 x institutional upper limit of normal (ULN) (obtained =\< 14 days prior to randomization)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (obtained =\< 14 days prior to randomization)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with treated brain metastases are eligible if neurologically stable without glucocorticoid therapy after the stated washout period from radiation therapy (RT) or surgery provided the metastatic lesions are non-hemorrhagic
* Patients with untreated brain metastases or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required provided the metastatic lesions are non-hemorrhagic and are neurologically stable without glucocorticoid therapy
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* Patient must have the ability to understand and the willingness to sign a written informed consent document and comply with study requirements
* Patient must not have had treatment with any investigational drug within five half-lives or 3 months (whichever is greater), prior to study initiation
* Patient must not be currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4. For any patient currently receiving such inducers of CYP3A4, they must discontinue use prior to first dose of study treatment. All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4
* Patient must not have any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of randomization, with the exception of alopecia and grade 2 prior platinum-therapy-related neuropathy
* Patient must not have any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it challenging for the patient to participate in the study. Screening for chronic conditions is not required
* Patient must not have refractory nausea and vomiting, chronic gastrointestinal diseases, the inability to swallow the osimertinib tablets or previous significant bowel resection that would preclude adequate absorption of osimertinib
* Patient must not have a medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
* Patient must not have a history of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib
* Patient must not have mean resting corrected QT interval (QTc) \> 470 msec obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value (using Bazett's correction)
* Patient must not have any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second-degree heart block
* Patient must not have any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities (including: potassium \< lower limit of normal \[LLN\]; magnesium \< LLN; calcium \< LLN), congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval and cause torsades de pointes BIOLOGICAL: Bevacizumab, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography Test, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Multigated Acquisition Scan, DRUG: Osimertinib
Advanced Lung Non-Squamous Non-Small Cell Carcinoma, Metastatic Lung Non-Squamous Non-Small Cell Carcinoma, Recurrent Lung Non-Squamous Non-Small Cell Carcinoma, Stage IIIB Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8, Lung/Thoracic
UT Southwestern; Parkland Health & Hospital System
A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma
This phase III trial compares the effect of selumetinib versus the standard of care treatment with carboplatin and vincristine (CV) in treating patients with newly diagnosed or previously untreated low-grade glioma (LGG) that does not have a genetic abnormality called BRAFV600E mutation and is not associated with systemic neurofibromatosis type 1. Selumetinib works by blocking some of the enzymes needed for cell growth and may kill tumor cells. Carboplatin and vincristine are chemotherapy drugs that work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. The overall goal of this study is to see if selumetinib works just as well as the standard treatment of CV for patients with LGG. Another goal of this study is to compare the effects of selumetinib versus CV in subjects with LGG to find out which is better. Additionally, this trial will also examine if treatment with selumetinib improves the quality of life for subjects who take it.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Bowers
ALL
2 Years to 21 Years old
PHASE3
NCT04166409
STU-2020-0013
Inclusion Criteria:
* Patients must be \>= 2 years and =\< 21 years at the time of enrollment
* Patients must have a body surface area (BSA) of \>= 0.5 m\^2 at enrollment
* Patients must have non-neurofibromatosis type 1 (non-NF1) low-grade glioma (LGG) without a BRAFV600E mutation as confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1 (NCT02402244) Childhood Cancer Data Initiative (CCDI)-MCI, or accepted Clinical Laboratory Improvement Amendments (CLIA)-certified test and that has not been treated with any modality besides surgery. Note: Patients may be newly-diagnosed OR previously diagnosed, and there is no required time frame between biopsy/surgery and treatment initiation.
* Patients with residual tumor after resection or progressive tumor after initial diagnosis (with or without surgery) who have not received treatment (chemotherapy and/or radiation) are eligible
* Patients must have two-dimensional measurable tumor \>= 1 cm\^2 to be eligible
* Patients with ependymoma are not eligible
* Eligible histologies will include all tumors considered low-grade glioma or low-grade astrocytoma (World Health Organization \[WHO\] grade I and II) by 5th edition WHO classification of central nervous system (CNS) tumors with the exception of subependymal giant cell astrocytoma
* Patients with metastatic disease or multiple independent primary LGG are eligible
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 OR a serum creatinine based on age/sex as follows (performed within 7 days prior to enrollment):
* Age: Maximum Serum Creatinine (mg/dL)
* 2 to \< 6 years: 0.8 mg/dL (male); 0.8 mg/dL (female)
* 6 to \< 10 years: 1 mg/dL (male); 1 mg/dL (female)
* 10 to \< 13 years: 1.2 mg/dL (male); 1.2 mg/dL (female)
* 13 to \< 16 years: 1.5 mg/dL (male); 1.4 mg/dL (female)
* \>= 16 years: 1.7 mg/dL (male); 1.4 mg/dL (female)
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment) (children with a diagnosis of Gilbert's syndrome will be allowed on study regardless of their total and indirect \[unconjugated\] bilirubin levels as long as their direct \[conjugated\] bilirubin is \< 3.1 mg/dL)
* Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (performed within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L
* Albumin \>= 2 g/dL (performed within 7 days prior to enrollment)
* Left ventricular ejection fraction (LVEF) \>= 53% (or institutional normal; if the LVEF result is given as a range of values, then the upper value of the range will be used) by echocardiogram (performed within 4 weeks prior to enrollment)
* Corrected QT (QTc) interval =\< 450 msec by electrocardiography (EKG) (performed within 4 weeks prior to enrollment)
* Absolute neutrophil count \>= 1,000/uL (unsupported) (performed within 7 days prior to enrollment)
* Platelets \>= 100,000/uL (unsupported) (performed within 7 days prior to enrollment)
* Hemoglobin \>= 8 g/dL (may be supported) (performed within 7 days prior to enrollment)
* Patients with a known seizure disorder must be stable and must not have experienced a significant increase in seizure frequency within 2 weeks prior to enrollment
* Patients 2-17 years of age must have a blood pressure that is =\< 95th percentile for age, height, and sex at the time of enrollment (with or without the use of anti-hypertensive medications)
* Patients \>= 18 years of age must have a blood pressure =\< 130/80 mmHg at the time of enrollment (with or without the use of anti-hypertensive medications)
* Note for patients of all ages: Adequate blood pressure can be achieved using medication for the treatment of hypertension
* All patients must have ophthalmology toxicity assessments performed within 8 weeks prior to enrollment
* For all patients, a magnetic resonance imaging (MRI) of the brain (with orbital cuts for optic pathway tumors) and/or spine (depending on the site(s) of primary disease) with and without contrast must be performed within 8 weeks prior to enrollment
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* Patients must have the ability to swallow whole capsules
* All patients have signed an appropriate consent form and Health Insurance Portability and Accountability Act (HIPAA) authorization form (if applicable)
* All patients and/or their parents or legal guardians must sign a written informed consent
* All patients have been consented and enrolled on APEC14B1 (NCT02402244) followed by enrollment on the ACNS1833 Pre-Enrollment Eligibility Screening (Step 0) on the same day to complete the Rapid Central Review
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
* Patients must not have received any prior tumor-directed therapy including chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant. Prior surgical intervention (with the exclusion of laser interstitial thermal therapy \[LITT\]) is permitted
* Patients with a concurrent malignancy or history of treatment (other than surgery) for another tumor within the last year are ineligible
* Patients with diffuse intrinsic pontine tumors as seen on MRI (\> 2/3 of pons involvement on imaging) are not eligible even if biopsy reveals grade I/II histology
* Patients may not be receiving any other investigational agents
* Patients with any serious medical or psychiatric illness/condition, including substance use disorders or ophthalmological conditions, likely in the judgment of the investigator to interfere or limit compliance with study requirements/treatment
* Patients who, in the opinion of the investigator, are not able to comply with the study procedures are not eligible
* Female patients who are pregnant are not eligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants are not eligible
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for 12 weeks after stopping study therapy are not eligible.
* Note: Women of child-bearing potential and males with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) should use effective methods of contraception for the duration of the study and for 12 weeks after stopping study therapy to avoid pregnancy and/or potential adverse effects on the developing embryo
* Known genetic disorder that increases risk for coronary artery disease. Note: The presence of dyslipidemia in a family with a history of myocardial infarction is not in itself an exclusion unless there is a known genetic disorder documented
* Symptomatic heart failure
* New York Health Association (NYHA) class II-IV prior or current cardiomyopathy
* Severe valvular heart disease
* History of atrial fibrillation
* Current or past history of central serous retinopathy
* Current or past history of retinal vein occlusion or retinal detachment
* Patients with uncontrolled glaucoma
* If checking pressure is clinically indicated, patients with intraocular pressure (IOP) \> 22 mmHg or ULN adjusted by age are not eligible
* Supplementation with vitamin E greater than 100% of the daily recommended dose. Any multivitamin containing vitamin E must be stopped prior to study enrollment even if less than 100% of the daily recommended dosing for vitamin E
* Surgery within 2 weeks prior to enrollment, with the exception of surgical biopsy, placement of a vascular access device or cerebral spinal fluid (CSF) diverting procedure such as endoscopic third ventriculostomy (ETV) and ventriculoperitoneal (VP) shunt.
* Note: Patients must have healed from any prior surgery
* Patients who have an uncontrolled infection are not eligible PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, PROCEDURE: Magnetic Resonance Imaging, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, DRUG: Selumetinib Sulfate, DRUG: Vincristine Sulfate
Low Grade Astrocytoma, Low Grade Glioma, Metastatic Low Grade Astrocytoma, Metastatic Low Grade Glioma, Brain and Nervous System
Children’s Health
Hyperinflation Respiratory Therapies in Cardiac Surgery Patients
The purpose of this prospective randomized clinical trial is to evaluate three different types of hyperinflation respiratory therapies, Intermittent Positive Pressure Breathing (IPPB), Intermittent positive end expiratory pressure (EzPAP), Metaneb. Investigators will examine which hyperinflation therapy provides better lung expansion and may improve lung recovery after surgery.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Emily.Melikman@UTSouthwestern.edu
Jaffer Odeh
ALL
18 Years to 80 Years old
NA
NCT04164173
STU-2019-1242
Inclusion Criteria:
• Age 18 years and older
• Admitted to Cardiovascular ICU (CVICU) after coronary artery bypass grafting (CABG), isolated valve repair/replacement, or CABG + valve repair/replacement
• Cardiac surgery performed via median sternotomy
Exclusion Criteria:
• BMI\>40
• Refusal to be consented
• Prior or current lung transplant patients
DEVICE: EzPAP, DEVICE: Metaneb, DEVICE: Intermittent Positive Pressure Breathing (IPPB)
Pulmonary Disease, Postoperative Complications, Cardiovascular
UT Southwestern
Testing the Addition of the Drug Apalutamide to the Usual Hormone Therapy and Radiation Therapy After Surgery for Prostate Cancer, INNOVATE Trial (INNOVATE)
This phase III trial studies whether adding apalutamide to the usual treatment improves outcome in patients with lymph node positive prostate cancer after surgery. Radiation therapy uses high energy x-ray to kill tumor cells and shrink tumors. Androgens, or male sex hormones, can cause the growth of prostate cancer cells. Drugs, such as apalutamide, may help stop or reduce the growth of prostate cancer cell growth by blocking the attachment of androgen to its receptors on cancer cells, a mechanism similar to stopping the entrance of a key into its lock. Adding apalutamide to the usual hormone therapy and radiation therapy after surgery may stabilize prostate cancer and prevent it from spreading and extend time without disease spreading compared to the usual approach.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Aurelie Garant
MALE
18 Years and over
PHASE3
NCT04134260
STU-2020-0570
Inclusion Criteria:
* Pathologically (histologically) proven diagnosis of prostate adenocarcinoma. Any type of radical prostatectomy is permitted, including retropubic, perineal, laparoscopic or robotically assisted
* Any T-stage is eligible (American Joint Committee on Cancer \[AJCC\] 8th edition \[ed\])
* Appropriate stage for study entry based on fluciclovine F-18 PET scan (FACBC, Axumin) F-18 prostate-specific membrane antigen (PSMA) PET (PyLarify) scan, Gallium-68 PSMA PET scan, flotufolastat F-18 PSMA PET scan (Posluma), or C-11 or F-18 Choline PET within 90 days prior to registration that is negative for distant metastatic (M1a, M1b, M1c) disease. For patients with PSA \< 0.20 ng/mL at time of registration, PET scan is recommended but not required
* Pathologically node positive disease with nodal involvement only in the pelvis in the prostatectomy specimen or nodal disease on imaging at time of recurrence (including external iliacs, internal iliacs, and/or obturator nodes); peri-prostatic and peri-rectal nodes can also be considered regional lymphadenopathy and are allowed
* History/physical examination within 90 days prior to registration
* Age \>= 18
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 90 days prior to registration
* Detectable PSA after radical prostatectomy. Detectable PSA is defined as serum PSA \> 0 ng/mL at least 30 days after prostatectomy
* Patients who have already started on post-prostatectomy GnRH agonist/antagonist for =\< 180 days prior to registration are eligible (Note: patients who started on an oral antiandrogen are eligible if started =\< 180 days and stopped prior to registration)
* Hemoglobin \>= 9.0 g/dL, independent of transfusion and/or growth factors (within 90 days prior to registration)
* Platelet count \>= 100,000 x 10\^9/uL independent of transfusion and/or growth factors (within 90 days prior to registration)
* Serum potassium \>= 3.5 mmol/L within 90 days prior to registration
* Creatinine clearance (CrCl) \>= 30 mL/min estimated by Cockcroft-Gault (please use actual weight for calculation unless greater than 30% above ideal body weight then use the adjusted body weight) (within 90 days prior to registration)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (Note: In subjects with Gilbert's syndrome, if total bilirubin is \> 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =\< 1.5 x ULN, subject is eligible) (within 90 days prior to registration)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (within 90 days prior to registration)
* Serum albumin \>= 3.0 g/dL (within 90 days prior to registration)
* Discontinue or substitute concomitant medications known to lower the seizure threshold at least 30 days prior to registration
* The patient must agree to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agree to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial and have a CD4 count \>= 200 cells/microliter within 30 days prior to registration. Note: HIV testing is not required for eligibility for this protocol
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy within 30 days prior to registration, if indicated. Note: HBV viral testing is not required for eligibility for this protocol
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load within 30 days prior to registration
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Note: Any patient with a cancer (other than keratinocyte carcinoma or carcinoma in situ) who has no evidence of disease for \< 3 years must contact the principal investigator, Ronald Chen, Doctor of Medicine (MD)
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
Exclusion Criteria:
* Definitive radiologic evidence of metastatic disease (M1a, M1b or M1c) on molecular imaging (e.g. Fluciclovine F-18 PET, \[FACBC, Axumin\], F-18 PSMA PET \[Pylarify\], flotufolastat F-18 PSMA PET scan \[Posluma\], Gallium-68 PSMA PET scan or C-11 choline PET)
* Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowed (completed \> 3 years prior to registration)
* Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
* Androgen deprivation therapy (ADT) prior to radical prostatectomy
* Prior treatment with androgen receptor signaling inhibitor (including but not exclusive to a growing list of: abiraterone acetate, enzalutamide, apalutamide, darolutamide), unless started =\< 180 days and stopped prior to registration, which is allowed
* Current use of 5-alpha reductase inhibitor. NOTE: if the alpha reductase inhibitor is stopped prior to randomization the patient is eligible
* History of any of the following:
* Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year prior to registration, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system \[CNS\] or meningeal disease which may require treatment with surgery or radiation therapy)
* Severe or unstable angina, myocardial infarction, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 12 months prior to registration
* New York Heart Association functional classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification.)
* History of any condition that in the opinion of the investigator, would preclude participation in this study
* Current evidence of any of the following:
* Known gastrointestinal disorder affecting absorption of oral medications
* Active uncontrolled infection
* Presence of uncontrolled hypertension (persistent systolic blood pressure \[BP\] \>= 160 mmHg or diastolic BP \>= 100 mmHg). Subjects with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment
* Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/prednisolone once daily
* Baseline moderate and severe hepatic impairment (Child-Pugh Class B \& C)
* Inability to swallow oral pills
* Any current condition that in the opinion of the investigator, would preclude participation in this study
* Patients must not plan to participate in any other therapeutic clinical trials while receiving treatment on this study
* Patients with inflammatory bowel disease DRUG: Apalutamide, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, DRUG: Hormone Therapy, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, RADIATION: Radiation Therapy
Prostate Adenocarcinoma, Stage I Prostate Cancer AJCC v8, Stage II Prostate Cancer AJCC v8, Stage III Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8, Prostate
Prostate Cancer, Apalutamide, Abiraterone Acetate
UT Southwestern; Parkland Health & Hospital System
A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-cell Maturation Antigen (BCMA) in Participants With Multiple Myeloma (CARTITUDE-2)
The purpose of this study is to evaluate the overall minimal residual disease (MRD) negative rate of participants who receive JNJ-68284528.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Aimaz Afrough
ALL
18 Years and over
PHASE2
NCT04133636
STU-2024-0107
Inclusion Criteria:
* Cohort A: Received a minimum of 1 to a maximum of 3 prior lines of therapy including a proteasome inhibitor (PI) and immunomodulatory therapy (IMiD), and lenalidomide refractory per International Myeloma Working Group (IMWG) guidelines
* Cohort B: Received one line of prior therapy including a PI and an IMiD, and disease progression per IMWG criteria less than or equal to (\<=) 12 months after treatment with autologous stem cell transplantation (ASCT) or \<=12 months from the start of anti-myeloma therapy for participants who have not had an ASCT
* Cohort C: Previously treated with a PI, an IMiD, an anti-CD38 monoclonal antibody and B-cell maturation antigen (BCMA)-directed therapy
* Cohort D: Newly diagnosed multiple myeloma per IMWG with a history of 4 to 8 total cycles of initial therapy, including induction, high-dose therapy, and ASCT with or without consolidation
* Cohort E: Have newly diagnosed multiple myeloma without prior therapy (one cycle of prior therapy before enrollment is acceptable) and classified as high risk defined as either: 1) International Staging System (ISS) stage III criteria, Beta 2 microglobulin greater than or equal to (\>=) 5.5 milligrams per liter (mg/L) (via local or central laboratory assessment) or 2) high risk cytogenetic features del(17/17p), t (14;16), t(14;20), 1q amplification (at least 4 total copies) in at least 20 percent (%) of the total plasma cell population
* Cohort F:
* Participant must have a documented efficacy response of very good partial response (VGPR) or better, without progressive disease prior to enrollment, as assessed per IMWG 2016 criteria
* Received initial therapy as specified below. The dose/schedule of cycles administered will be as per standard of care. It is acceptable for up to 1 cycle of the protocol-specified regimens to be missing one of the listed agents (example, held due to toxicity). Acceptable combinations include: At least 5 to 8 cycles of initial therapy with daratumumab, bortezomib, lenalidomide and dexamethasone (D-VRd). The dose/schedule of cycles administered will be as per standard of care or; at least 4 to 8 cycles of initial therapy with daratumumab, lenalidomide and dexamethasone (D-Rd) or; at least 4 to 8 cycles of initial therapy with a carfilzomib-based triplet or quadruplet regimen
* Cohort G: Not considered for high-dose chemotherapy with autologous stem cell transplantation (ASCT) due to: a) Ineligibility due to advanced age; or b) Ineligibility due to presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with ASCT; or c) Subject refusal of high-dose chemotherapy with ASCT as initial treatment
* Cohort H: Considered a candidate for high-dose chemotherapy with ASCT as initial treatment
* Cohorts A, B, C, E, G, H:
* Serum monoclonal paraprotein (M-protein) level greater than or equal to (\>=) 1.0 gram per deciliter (g/dL) or urine M-protein level \>=200 milligrams (mg)/24 hours
* Light chain multiple myeloma in whom only measurable disease is by serum free light chain (FLC) levels in the serum: Serum immunoglobulin FLC \>=10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio
* Cohort A: For participants with neither serum nor urine measurable disease, baseline positron emission tomography/ computed tomography (PET/CT) or whole -body magnetic resonance imaging (MRI) may be used to satisfy the measurable disease criteria. A minimum of one lesion with a bi-dimensional measurement of at least 1 centimeter (cm)\*1 cm is required
* Cohorts B, C: For participants with neither serum nor urine measurable disease, baseline positron emission tomography/ computed tomography (PET/CT) or whole body magnetic resonance imaging (MRI) may be used to satisfy the measurable disease criteria
* Cohorts A, B, C, D, E, F, G, H: Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
Exclusion Criteria:
* Cohorts A, B, D, F: Any therapy that is targeted to BCMA
* Cohorts A, B, C, D, F: Prior treatment with chimeric antigen receptor T (CAR-T) therapy directed at any target
* Cohorts A, B, C, D, F:
* Ongoing toxicity from previous anticancer therapy must resolve to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy
* Received a cumulative dose of corticosteroids equivalent to \>=70 mg of prednisone within the 7 days (Cohort A, B, C, F) or 14 days (Cohort D) prior to apheresis
* Serious underlying medical condition, such as (a) evidence of active viral or bacterial infection requiring systemic antimicrobial therapy, or uncontrolled systemic fungal infection; (b) active autoimmune disease or a history of autoimmune disease within 3 years; (c) overt clinical evidence of dementia or altered mental status; (d) any history of Parkinson's disease or other neurodegenerative disorder
* Cohorts A, B, C, D, E, F: Known active, or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma
* Cohorts F, G, and H: Active malignancies (that is, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions are: a) non-muscle invasive bladder cancer treated within the last 24 months that is considered completely cured; b) skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured; c) non-invasive cervical cancer treated within the last 24 months that is considered completely cured; d) localized prostate cancer (N0M0): with a Gleason score of greater than or equal to (=\>)6, treated within the last 24 months or untreated and under surveillance, with a Gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence, or history of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence, e) breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence; f) malignancy that is considered cured with minimal risk of recurrence
* Cohorts E, G, and H: Frailty index of \>= 2 according to Myeloma Geriatric Assessment score DRUG: JNJ-68284528, DRUG: Lenalidomide, DRUG: Daratumumab, DRUG: Bortezomib, DRUG: Dexamethasone
Multiple Myeloma
Cellular Therapy, CAR-T Therapy, BCMA CAR-T
UT Southwestern
Study to Learn More About the Safety and Effectiveness of the Drug VITRAKVI During Routine Use in Patients With TRK Fusion Cancer Which is Locally Advanced or Spread From the Place Where it Started to Other Places in the Body (ON-TRK)
In this observational study researcher want to learn more about the effectiveness of drug VITRAKVI (generic name: larotrectinib) and how well the drug is tolerated during routine use in patients with TRK fusion cancer which is locally advanced or spread from the place where it started to other places in the body. TRK fusion cancer is a term used to describe a variety of common and rare cancers that are caused by a change to the NTRK (Neurotrophic Tyrosine Kinase) gene called a fusion. During this fusion, an NTRK gene joins together, or fuses, with a different gene. This joining results in the activation of certain proteins (TRK fusion proteins), which can cause cancer cells to multiply and form a tumor. VITRAKVI is an approved drug that blocks the action of the NTRK gene fusion. This study will enroll adult and paediatric patients suffering from a solid tumor with NTRK gene fusion for whom the decision to treat their disease with VITRAKVI has been made by their treating physicians. During the study, patients' medical information such as treatment information with VITRAKVI, other medication or treatments, changes in disease status and other health signs and symptoms will be collected within the normal medical care by the treating doctor. Participants will be observed over a period from 24 to 60 months.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tanya Watt
ALL
1 Month and over
NCT04142437
STU-2019-0998
Inclusion Criteria:
* Adult and pediatric (from birth to 18-year-old) patients
* Patients with locally advanced or metastatic solid tumor harboring an NTRK gene fusion. NTRK (NTRK1, NTRK2, and NTRK3) gene fusions will be identified locally. Acceptable methods of detection of NTRK gene fusion include NGS, fluorescence in situ hybridization (FISH), reverse-transcription polymerase chain reaction (rt-PCR) or any other genomic testing able to detect NTRK gene fusion. If a pan-TRK IHC method is used, this result needs to be accompanied with the results using one of the other methods noted above.
* Life expectancy of at least 3 months based on clinical judgement
* Decision to treat with larotrectinib made by the treating physician prior to study enrollment
* Patients can also be enrolled if the initial visit (larotrectinib start date) occurred within 2 months ±3 days prior to informed consent signed date
* Signed informed consent form
* For patients under legal age, signed assent by the patient (where applicable) and parental/legal guardian signed informed consent is required
Exclusion Criteria:
* Any contraindications as listed in the local approved product information
* Pregnancy
* Participation in an investigational program with interventions outside of routine clinical practice
* Prior treatment with larotrectinib or other kinase inhibitor with TRK inhibition
* Patients with NTRK gene amplification or NTRK point mutation DRUG: larotrectinib(Vitrakvi, BAY2757556)
Locally Advanced or Metastatic Solid Tumor Harboring an NTRK Gene Fusion, Bones and Joints, Brain and Nervous System, Eye and Orbit, Kidney, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Other Digestive Organ, Other Endocrine System, Other Male Genital, Other Respiratory and Intrathoracic Organs, Soft Tissue, Unknown Sites
UT Southwestern; Children’s Health
A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations
Phase 1 will evaluate the safety and tolerability at different dose levels of repotrectinib in pediatric and young adult subjects with advanced or metastatic malignancies harboring anaplastic lymphoma kinase (ALK), receptor tyrosine kinase encoded by the gene ROS1 (ROS1), or neurotrophic receptor kinase genes encoding TRK kinase family (NTRK1-3) alterations to estimate the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) and select the Pediatric Recommended Phase 2 Dose (RP2D). Phase 2 will determine the anti-tumor activity of repotrectinib in pediatric and young adult subjects with advanced or metastatic malignancies harboring ROS1 or NTRK1-3 alterations.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tanya Watt
ALL
up to 25 Years old
PHASE1
NCT04094610
STU-2019-1268
Key
• Documented genetic ROS1 point mutation, fusion, or amplification or NTRK1-3 fusion as identified by local testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory in the US or equivalently accredited diagnostic lab outside the United States (US) is required.
• Phase 1: Age \<12 years; Phase 2: Age 12- 25 years
• Prior cytotoxic chemotherapy is allowed.
• Prior immunotherapy is allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• All subjects must have measurable disease by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) criteria at time of enrollment.
• Subjects with a primary CNS tumor or CNS metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 7 days prior to enrollment.
• Subjects must have a Lansky (\< 16 years) or Karnofsky (≥ 16 years) score of at least 50.
• Life expectancy greater than or equal to 12 weeks, in the investigator's opinion.
• Adequate hematologic, renal and hepatic function. Phase 2
• Cohort Specific
• Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment. Key Exclusion Criteria (Phase 1 and Phase 2):
• Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
• Major surgery within 14 days (2 weeks) of start of repotrectinib treatment. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery.
• Known active infections requiring ongoing treatment (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
• Any of the following cardiac criteria: * Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) \> 480 msec obtained from three ECGs, using the screening clinic ECG machine-derived QTc value * Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval \> 250 msec) * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval
• Peripheral neuropathy of CTCAE ≥grade 2.
• Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.
• Any potential allergies to repotrectinib and/or its excipients.
Inclusion Criteria:
• Documented genetic ROS1 point mutation, fusion, or amplification or NTRK1-3 fusion as identified by local testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory in the US or equivalently accredited diagnostic lab outside the United States (US) is required.
• Phase 1: Age \<12 years; Phase 2: Age 12- 25 years
• Prior cytotoxic chemotherapy is allowed.
• Prior immunotherapy is allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• All subjects must have measurable disease by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) criteria at time of enrollment.
• Subjects with a primary CNS tumor or CNS metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 7 days prior to enrollment.
• Subjects must have a Lansky (\< 16 years) or Karnofsky (≥ 16 years) score of at least 50.
• Life expectancy greater than or equal to 12 weeks, in the investigator's opinion.
• Adequate hematologic, renal and hepatic function. Phase 2
Inclusion Criteria:
• Cohort Specific
Inclusion Criteria:
* Cohort 1: Subjects with NTRK fusion gene positive (NTRK+) advanced solid tumors (including primary CNS tumors), that are tropomyosin receptor kinase (TRK) TKI naïve;
* Cohort 2: subjects with NTRK+ advanced solid tumors (including primary CNS tumors), that are TRK TKI pre-treated;
* Cohort 3: subjects with advanced solid tumors with ROS1 gene fusions or other ROS1 aberrations (including amplifications and point mutations) with measurable disease.
• Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment. Key Exclusion Criteria (Phase 1 and Phase 2):
• Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
• Major surgery within 14 days (2 weeks) of start of repotrectinib treatment. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery.
• Known active infections requiring ongoing treatment (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
• Any of the following cardiac criteria: * Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) \> 480 msec obtained from three ECGs, using the screening clinic ECG machine-derived QTc value * Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval \> 250 msec) * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval
• Peripheral neuropathy of CTCAE ≥grade 2.
• Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.
• Any potential allergies to repotrectinib and/or its excipients.
DRUG: Oral repotrectinib (TPX-0005)
Locally Advanced Solid Tumors, Metastatic Solid Tumors, Lymphoma, Primary CNS Tumors, Breast - Female, Breast - Male, Colon, Kidney, Lung/Thoracic, Rectum, Soft Tissue, Thyroid, Urinary Bladder
ALK, ROS1, NTRK1-3, Primary CNS tumor, anaplastic large cell lymphoma, metastatic solid tumor, advanced solid tumor, sarcoma, infantile fibrosarcoma, glioblastoma, soft tissue schwannoma, solitary fibrous tumor, glioma, inflammatory myofibroblastic tumor, pediatric
Children’s Health
Cobimetinib in Refractory Langerhans Cell Histiocytosis (LCH), and Other Histiocytic Disorders (NACHO-COBI)
This is a research study of a drug called cobimetinib in children and adults diagnosed with Langerhans cell histiocytosis (LCH), and other histiocytic disorders that has returned or does not respond to treatment. Cobimetinib blocks activation of a protein called Mitogen-activated protein kinase (MEK) that is part of incorrect growth signals in histiocytosis cells. Four different groups of patients will be enrolled.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Erin Butler
All
Not specified
Phase 2
NCT04079179
STU-2021-0830
INCLUSION CRITERIA:
Age at study entry
• For Group 1: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 2: Participant may be at least 6 months of age at the time of enrollment
• For Group 3: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 4: Participant must be 21 years of age or older at the time of enrollment
• Participant must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet which may be taken by mouth or other enteral route such as nasogastric or gastric tube.
• Biopsy proven LCH -AND
• Failure of at least front-line therapy for LCH with evaluable disease. -OR
• Diagnosis of LCH-associated neurodegenerative disease with radiologic or clinical progression within the past 3 months. -OR
• Biopsy proven JXG, ECD, RDD, histiocytic sarcoma, or other histiocytic lesion (newly diagnosed or relapsed/refractory disease) with evaluable active disease. Performance Level: -Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age. Adequate Hematologic Function Defined as:
• ANC ≥ 0.75 x 10^9/L (unsupported/without growth factor stimulant)
• Platelet count ≥ 75 x 10^9/L (unsupported/without transfusion within the past 7 days).
• Patients with marrow disease must have platelet count of >/= 75 x 10^9/L (transfusion support allowed) and must not be refractory to platelet transfusions.
• Hemoglobin ≥ 8 g/dL (unsupported/without transfusion within the past 7 days)
• Patients with marrow disease must have hemoglobin ≥ 8 g/dL (transfusion support allowed). Adequate Renal Function Defined as:
• Calculated creatinine clearance (or radioisotope GFR) ≥ 70 mL/min/1.73m^2 or serum creatinine based on age/gender as follows: Maximum Serum Creatinine (mg/dL) Age 2 to < 6 years: Male 0.8 mg/d, Female 0.8; 6 to < 10 years: Male 1 mg/dL,Female 1; 10 to < 13 years: Male 1.2 mg/dL; Female 1.2; 13 to < 16 years: Male 1.5 mg/dL ; Female 1.4; ≥ 16 years: Male 1.7 mg/dL; Female 1.4; Adequate Liver Function Defined as:
• Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
• AST and ALT ≤ 3x ULN (≤ 5 x ULN for participants with liver involvement)
• Serum albumin ≥ 2 g/dL. For patients with liver disease caused by histiocytic disorder: • Patients may be enrolled with abnormal bilirubin, AST, ALT and albumin with documentation of histiocytic liver disease. Adequate Cardiac Function Defined as:
• Fractional shortening (FS) of ≥ 30% or ejection fraction of ≥ 50% by echocardiogram at baseline, as determined by echocardiography or multigated acquisition scan (MUGA) within 28 days prior to enrollment. Depending on institutional standard, either FS or LVEF is adequate for enrollment if only one value is measured; if both values are measured, then both values must meet criteria above Pregnancy/Birth Control
• Female patients of childbearing potential require a negative urine or serum pregnancy test for eligibility and again at database registration, if more than 2 weeks has elapsed.
• Female patients of childbearing potential must agree to follow the contraceptive requirements using two forms of effective contraceptive methods for the duration of the study treatment. Male patients with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) must agree to use two forms of effective methods of contraception (one of which must be a barrier method) during the treatment period and for at least 3 months after the last dose of the study drug to avoid pregnancy and/or potential adverse effects on a developing embryo. Agreement to true abstinence (not periodic abstinence or withdrawal method) is an acceptable method of birth control. EXCLUSION CRITERIA:
• Prior and Concomitant Use of Drugs with CYP3A4 inducing/inhibiting activity: Patient taking strong inducers or inhibitors of CYP3A4 within 14 days prior to study enrollment, including but not limited to the following: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort.
• Prior Therapy Restrictions Completion of previous chemotherapy, immunotherapy, radiotherapy, or targeted therapy for LCH (or other histiocytic disorder) at least 28 days (except where specified below) prior to study enrollment, with resolution of all associated toxicity to ≤ Grade 1 prior to study enrollment (exception for alopecia and ototoxicity which do not need to be resolved ≤ Grade 1). Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the laboratory eligibility criteria are met, the patient is considered to have recovered adequately.
• Radiation therapy within the 28 days prior to enrollment.
• Any prior treatment with Cobimetinib.
• Treatment with a long-acting hematopoietic growth factor within 14 days prior to initiation of study drug or a short-acting hematopoietic growth factor within 7 days prior to enrollment.
• Treatment with hormonal therapy (except hormone replacement therapy or oral contraceptives), immunotherapy, biologic therapy, investigational therapy, or herbal cancer therapy within 28 days or < 5 half-lives, whichever is longer, prior to study enrollment.
• Treatment with high-dose chemotherapy and stem-cell rescue (autologous stem cell transplant) or allogeneic stem cell transplant within 90 days prior to enrollment. Anti-GVHD agents post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial.
• For patients with brain tumors (intracranial masses), use of anticoagulants within 7 days prior to enrollment.
• Corticosteroid therapy <0.5 mg/kg/day averaged during the month prior to study enrollment is permissible but must be discontinued fourteen (14) days prior to enrollment. Patients with documented brain lesions receiving corticosteroids for management of cerebral edema must be on a stable dose for fourteen (14) days prior to enrollment.
• Patient has received treatment with investigational therapy within 4 weeks prior to initiation of study drug.
• Patients taking anticoagulants or have a pre-existing bleeding disorder unrelated to histiocytic disease.
• Exclusions for other illness
• Other active malignancy or history of secondary malignancy.
• Refractory nausea and vomiting, malabsorption, external biliary shunt
• Infection: Patients who have a known active infection (excluding documented fungal infection of the nail beds) within 28 days prior to enrollment that has not completely resolved.
• Major surgical procedure or significant traumatic injury within 28 days prior to enrollment, or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted within fourteen (14) days prior to study enrollment (provided that the wound has healed).
• History of significant bowel resection that would preclude adequate absorption or other significant malabsorptive disease.
• History of pneumonitis.
• Ophthalmologic considerations: Patients with known significant ophthalmologic conditions or known risk factors for retinal vein occlusion are not eligible. Specifically, patients with a history of retinal vein occlusion (RVO), retinal detachment, retinal pathology on ophthalmologic exam, retinopathy of prematurity, central serous chorioretinopathy (CSSCR), neovascular retinopathy, intraocular pressure > 21 mmHg, and predisposing factors to RVO (e.g., uncontrolled hypertension, diabetes, or hyperlipidemia, coagulopathy) will be excluded. Patients with longstanding and stable ophthalmologic findings secondary to existing conditions are eligible with appropriate written documentation and approval from Study Chair.
• History of solid organ transplantation: Patients who have received a prior solid organ transplantation are not eligible.
• Any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that in the opinion of the investigator contraindicates use of an investigational drug or places the patient at unacceptable risk from treatment complications.
• History of clinically significant cardiac dysfunction, including the following:
• Clinically significant cardiac arrhythmias including brady-arrhythmias and/or patients who require anti-arrhythmic therapy (with the exception of beta blockers or digoxin). Patients with controlled atrial fibrillation are not excluded.
• Unstable arrhythmia
• Unstable angina, or new-onset angina within 3 months prior to initiation of study treatment
• Symptomatic congestive heart failure, defined as New York Heart Association Class II or higher
• Myocardial infarction within 3 months prior to initiation of study treatment
• Known chronic human immunodeficiency virus (HIV).
• History of Grade ≥ 2 CNS hemorrhage or history of any CNS hemorrhage within 28 days of enrollment.
• Female patients who are pregnant or lactating. Pregnant or lactating women will not be entered on this study because there is no available information regarding human fetal or teratogenic toxicities.
• For Group 1: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 2: Participant may be at least 6 months of age at the time of enrollment
• For Group 3: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 4: Participant must be 21 years of age or older at the time of enrollment
• Participant must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet which may be taken by mouth or other enteral route such as nasogastric or gastric tube.
• Biopsy proven LCH -AND
• Failure of at least front-line therapy for LCH with evaluable disease. -OR
• Diagnosis of LCH-associated neurodegenerative disease with radiologic or clinical progression within the past 3 months. -OR
• Biopsy proven JXG, ECD, RDD, histiocytic sarcoma, or other histiocytic lesion (newly diagnosed or relapsed/refractory disease) with evaluable active disease. Performance Level: -Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age. Adequate Hematologic Function Defined as:
• ANC ≥ 0.75 x 10^9/L (unsupported/without growth factor stimulant)
• Platelet count ≥ 75 x 10^9/L (unsupported/without transfusion within the past 7 days).
• Patients with marrow disease must have platelet count of >/= 75 x 10^9/L (transfusion support allowed) and must not be refractory to platelet transfusions.
• Hemoglobin ≥ 8 g/dL (unsupported/without transfusion within the past 7 days)
• Patients with marrow disease must have hemoglobin ≥ 8 g/dL (transfusion support allowed). Adequate Renal Function Defined as:
• Calculated creatinine clearance (or radioisotope GFR) ≥ 70 mL/min/1.73m^2 or serum creatinine based on age/gender as follows: Maximum Serum Creatinine (mg/dL) Age 2 to < 6 years: Male 0.8 mg/d, Female 0.8; 6 to < 10 years: Male 1 mg/dL,Female 1; 10 to < 13 years: Male 1.2 mg/dL; Female 1.2; 13 to < 16 years: Male 1.5 mg/dL ; Female 1.4; ≥ 16 years: Male 1.7 mg/dL; Female 1.4; Adequate Liver Function Defined as:
• Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
• AST and ALT ≤ 3x ULN (≤ 5 x ULN for participants with liver involvement)
• Serum albumin ≥ 2 g/dL. For patients with liver disease caused by histiocytic disorder: • Patients may be enrolled with abnormal bilirubin, AST, ALT and albumin with documentation of histiocytic liver disease. Adequate Cardiac Function Defined as:
• Fractional shortening (FS) of ≥ 30% or ejection fraction of ≥ 50% by echocardiogram at baseline, as determined by echocardiography or multigated acquisition scan (MUGA) within 28 days prior to enrollment. Depending on institutional standard, either FS or LVEF is adequate for enrollment if only one value is measured; if both values are measured, then both values must meet criteria above Pregnancy/Birth Control
• Female patients of childbearing potential require a negative urine or serum pregnancy test for eligibility and again at database registration, if more than 2 weeks has elapsed.
• Female patients of childbearing potential must agree to follow the contraceptive requirements using two forms of effective contraceptive methods for the duration of the study treatment. Male patients with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) must agree to use two forms of effective methods of contraception (one of which must be a barrier method) during the treatment period and for at least 3 months after the last dose of the study drug to avoid pregnancy and/or potential adverse effects on a developing embryo. Agreement to true abstinence (not periodic abstinence or withdrawal method) is an acceptable method of birth control. EXCLUSION CRITERIA:
• Prior and Concomitant Use of Drugs with CYP3A4 inducing/inhibiting activity: Patient taking strong inducers or inhibitors of CYP3A4 within 14 days prior to study enrollment, including but not limited to the following: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort.
• Prior Therapy Restrictions Completion of previous chemotherapy, immunotherapy, radiotherapy, or targeted therapy for LCH (or other histiocytic disorder) at least 28 days (except where specified below) prior to study enrollment, with resolution of all associated toxicity to ≤ Grade 1 prior to study enrollment (exception for alopecia and ototoxicity which do not need to be resolved ≤ Grade 1). Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the laboratory eligibility criteria are met, the patient is considered to have recovered adequately.
• Radiation therapy within the 28 days prior to enrollment.
• Any prior treatment with Cobimetinib.
• Treatment with a long-acting hematopoietic growth factor within 14 days prior to initiation of study drug or a short-acting hematopoietic growth factor within 7 days prior to enrollment.
• Treatment with hormonal therapy (except hormone replacement therapy or oral contraceptives), immunotherapy, biologic therapy, investigational therapy, or herbal cancer therapy within 28 days or < 5 half-lives, whichever is longer, prior to study enrollment.
• Treatment with high-dose chemotherapy and stem-cell rescue (autologous stem cell transplant) or allogeneic stem cell transplant within 90 days prior to enrollment. Anti-GVHD agents post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial.
• For patients with brain tumors (intracranial masses), use of anticoagulants within 7 days prior to enrollment.
• Corticosteroid therapy <0.5 mg/kg/day averaged during the month prior to study enrollment is permissible but must be discontinued fourteen (14) days prior to enrollment. Patients with documented brain lesions receiving corticosteroids for management of cerebral edema must be on a stable dose for fourteen (14) days prior to enrollment.
• Patient has received treatment with investigational therapy within 4 weeks prior to initiation of study drug.
• Patients taking anticoagulants or have a pre-existing bleeding disorder unrelated to histiocytic disease.
• Exclusions for other illness
• Other active malignancy or history of secondary malignancy.
• Refractory nausea and vomiting, malabsorption, external biliary shunt
• Infection: Patients who have a known active infection (excluding documented fungal infection of the nail beds) within 28 days prior to enrollment that has not completely resolved.
• Major surgical procedure or significant traumatic injury within 28 days prior to enrollment, or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted within fourteen (14) days prior to study enrollment (provided that the wound has healed).
• History of significant bowel resection that would preclude adequate absorption or other significant malabsorptive disease.
• History of pneumonitis.
• Ophthalmologic considerations: Patients with known significant ophthalmologic conditions or known risk factors for retinal vein occlusion are not eligible. Specifically, patients with a history of retinal vein occlusion (RVO), retinal detachment, retinal pathology on ophthalmologic exam, retinopathy of prematurity, central serous chorioretinopathy (CSSCR), neovascular retinopathy, intraocular pressure > 21 mmHg, and predisposing factors to RVO (e.g., uncontrolled hypertension, diabetes, or hyperlipidemia, coagulopathy) will be excluded. Patients with longstanding and stable ophthalmologic findings secondary to existing conditions are eligible with appropriate written documentation and approval from Study Chair.
• History of solid organ transplantation: Patients who have received a prior solid organ transplantation are not eligible.
• Any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that in the opinion of the investigator contraindicates use of an investigational drug or places the patient at unacceptable risk from treatment complications.
• History of clinically significant cardiac dysfunction, including the following:
• Clinically significant cardiac arrhythmias including brady-arrhythmias and/or patients who require anti-arrhythmic therapy (with the exception of beta blockers or digoxin). Patients with controlled atrial fibrillation are not excluded.
• Unstable arrhythmia
• Unstable angina, or new-onset angina within 3 months prior to initiation of study treatment
• Symptomatic congestive heart failure, defined as New York Heart Association Class II or higher
• Myocardial infarction within 3 months prior to initiation of study treatment
• Known chronic human immunodeficiency virus (HIV).
• History of Grade ≥ 2 CNS hemorrhage or history of any CNS hemorrhage within 28 days of enrollment.
• Female patients who are pregnant or lactating. Pregnant or lactating women will not be entered on this study because there is no available information regarding human fetal or teratogenic toxicities.
Drug: Cobimetinib
Langerhan's Cell Histiocytosis, Juvenile Xanthogranuloma, Erdheim-Chester Disease, Rosai Dorfman Disease, Neuro-Degenerative Disease, Histiocytic Sarcoma, Histiocytic Disorders, Malignant, Bones and Joints, Brain and Nervous System, Liver, Lung/Thoracic, Other Hematopoietic
Cobimetinib, Langerhans Cell Histiocytosis (LCH)
Children’s Health
Testing the Addition of a New Anti-cancer Drug, Radium-223 Dichloride, to the Usual Treatment (Cabozantinib) for Advanced Renal Cell Cancer That Has Spread to the Bone, RadiCaL Study
This phase II trial studies whether adding radium-223 dichloride to the usual treatment, cabozantinib, improves outcomes in patients with renal cell cancer that has spread to the bone. Radioactive drugs such as radium-223 dichloride may directly target radiation to cancer cells and minimize harm to normal cells. Cabozantinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving radium-223 dichloride and cabozantinib may help lessen the pain and symptoms from renal cell cancer that has spread to the bone, compared to cabozantinib alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
ALL
18 Years and over
PHASE2
NCT04071223
STU-2020-0639
Inclusion Criteria:
* Documented histologic or cytologic diagnosis of renal cell cancer (RCC). All subtypes of RCC are eligible including but not limited to clear cell, papillary, chromophobe, translocation, collecting duct carcinoma, medullary carcinoma, and unclassified categories. Enrollment of non-clear cell patients will be limited to 20% of the total sample size (\~ 42 patients). Once this goal is met, accrual of non-clear cell patients will be discontinued (a notice will be sent out 2 weeks in advance). Sarcomatoid and rhabdoid differentiation are allowed
* Presence of at least 1 metastatic bone lesion not treated with prior radiation is required.
* The presence of bone metastases can be detected by computed tomography (CT), magnetic resonance imaging (MRI), Tc-99m bone scan or positron emission tomography (PET) (fludeoxyglucose F-18 \[FDG\] or sodium fluoride \[NaF\]) imaging. Patients with non-measurable bone-only disease are allowed. Patients may have received prior radiation therapy for bone metastases or other external radiation \>= 7 days prior to registration, as long as they still have at least 1 metastatic bone lesion not treated with radiation. Patients with visceral metastases are allowed, as long as they have at least one untreated bone metastases
* No prior treatment with cabozantinib
* No treatment with any type of small molecular kinase inhibitor (including investigational kinase inhibitors) within 2 weeks or 5 half-lives (whichever is shorter) of registration or receipt of any anti-cancer therapy (including investigational therapy, monoclonal antibodies, cytokine therapy) within 3 weeks of registration
* No prior hemibody external radiotherapy
* No prior therapy with radium-223 dichloride or systemic radiotherapy (such as samarium, strontium)
* No major surgery within 6 weeks of randomization. Procedures such as thoracentesis, paracentesis, percutaneous biopsy, Moh's or other topical skin surgery, Lasik eye surgery are not considered major surgery. Patients who have had a nephrectomy may be registered \>= 3 weeks after surgery, providing there are no wound-healing complications. Subjects with clinically relevant ongoing complications from prior surgery are not eligible
* Recovery to baseline or =\< grade 1 CTCAE version 5.0 from toxicity related to any prior treatment, unless adverse events are clinically nonsignificant and/or stable on supportive therapy
* The use of osteoclast targeted therapy including either bisphosphonates or denosumab is mandated on this study except in patients with contraindications as determined by the treating investigator, including:
* Hypocalcemia
* Hypophosphatemia
* Renal impairment including those with a glomerular filtration rate (GFR) \< 35 mL/min using the Cockcroft-Gault equation or acute renal impairment
* Hypersensitivity to drug formulation
* Dental condition or need for dental intervention that per the investigator would increase the risk of osteonecrosis of jaw (ONJ).
* Use of osteoclast targeted therapy or reason against use needs to be recorded in the electronic case report form (eCRF). Additionally, reason for discontinuation of osteoclast targeted therapy need to be appropriately documented in the eCRF
* Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown.
* Therefore, for women of childbearing potential only, a negative urine pregnancy test done =\< 28 days prior to registration is required. A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
* Age \>= 18 years
* Karnofsky performance status \>= 60%
* No brain metastases or cranial epidural disease unless adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator. Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator
* No imminent or established spinal cord compression based on clinical symptoms and/or imaging. In patients with untreated imminent or established spinal cord compression, treatment with standard of care as clinically indicated should be completed at least 2 weeks before registration
* No imminent or impending pathologic fracture based on clinical symptoms and/or imaging. In patients with untreated imminent or impending pathologic fracture, treatment with standard of care as clinically indicated should be completed at least 2 weeks before registration
* No significant, uncontrolled intercurrent or recent illness, including but not limited to the following conditions:
* Cardiovascular disorders: Symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia; uncontrolled hypertension defined as sustained blood pressure \> 150 mm Hg systolic or \> 100 mm Hg diastolic despite optimal antihypertensive treatment; stroke (including transient ischemic attack), myocardial infarction, or other ischemic event, within 6 months before randomization; thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 1 month before randomization
* Gastrointestinal disorders: Disorders associated with a high risk of perforation or fistula formation: active inflammatory bowel disease, active diverticulitis, active cholecystitis, active symptomatic cholangitis or active appendicitis, active acute pancreatitis or active acute obstruction of the pancreatic or biliary duct, or active gastric outlet obstruction; abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 3 months before randomization. Note: Complete healing of an intra-abdominal abscess must be confirmed before randomization
* No clinically significant hematuria, hematemesis, or hemoptysis, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 3 months before randomization
* No lesions invading major pulmonary blood vessels
* No other clinically significant disorders:
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy (with no medications prohibited by this protocol \[e.g. drug-drug interactions\]) with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy (with no medications prohibited by this protocol \[e.g. drug-drug interactions\]), if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load (with no medications prohibited by this protocol \[e.g. drug-drug interactions\])
* No serious non-healing wound or ulcer
* No malabsorption syndrome
* No uncompensated/symptomatic hypothyroidism
* No moderate to severe hepatic impairment (Child-Pugh B or C)
* No requirements for hemodialysis or peritoneal dialysis
* No history of solid organ transplantation
* No chronic concomitant treatment with strong CYP3A4 inducers or inhibitors. Because the list of these agents is constantly changing, it is important to regularly consult a frequently updated medical reference. Patients may not have received a strong CYP3A4 inducer within 12 days prior to registration nor a strong CYP3A4 inhibitor within 7 days prior to registration
* No concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants include:
* Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
* Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Hemoglobin \>= 9 g/dl (transfusions allowed)
* Calculated (calc.) creatinine clearance \>= 30 mL/min using the Cockcroft-Gault equation
* Total bilirubin =\< 1.5 x upper limit of normal (ULN), for patients with Gilberts disease =\< 3.0 x ULN
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3.0 x ULN
* Urine protein to creatinine (UPC) ratio =\< 2 mg/mg OR 24-hr urine protein \< 2 g PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, DRUG: Cabozantinib S-malate, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, RADIATION: Radium Ra 223 Dichloride
Advanced Renal Cell Carcinoma, Chromophobe Renal Cell Carcinoma, Clear Cell Renal Cell Carcinoma, Collecting Duct Carcinoma, Kidney Medullary Carcinoma, Metastatic Malignant Neoplasm in the Bone, Papillary Renal Cell Carcinoma, Stage IV Renal Cell Cancer AJCC v8, Unclassified Renal Cell Carcinoma, Kidney
UT Southwestern
Radiation Medication (Radium-223 Dichloride) Versus Radium-223 Dichloride Plus Radiation Enhancing Medication (M3814) Versus Radium-223 Dichloride Plus M3814 Plus Avelumab (a Type of Immunotherapy) for Advanced Prostate Cancer Not Responsive to Hormonal Therapy
This phase I/II trial studies the best dose of M3814 when given together with radium-223 dichloride or with radium-223 dichloride and avelumab and to see how well they work in treating patients with castrate-resistant prostate cancer that had spread to other places in the body (metastatic). M3814 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radioactive drugs, such as radium-223 dichloride, may carry radiation directly to tumor cells and not harm normal cells. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This study is being done to find out the better treatment between radium-223 dichloride alone, radium-223 dichloride in combination with M3814, or radium-223 dichloride in combination with both M3814 and avelumab, to lower the chance of prostate cancer growing or spreading in the bone, and if this approach is better or worse than the usual approach for advanced prostate cancer not responsive to hormonal therapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kevin Courtney
MALE
18 Years and over
PHASE1
NCT04071236
STU-2021-1040
Inclusion Criteria:
* PHASE 1: Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
* PHASE 2: ECOG performance status =\< 2 (Karnofsky \>= 60%)
* Unless a patient has had orchiectomy by surgery, the patient is expected to be on antiandrogen therapy (ADT) for "medical castration". ADT needs to be maintained throughout the study. Testosterone level should be checked, and kept consistently lower than 50 ng/dL, similar to that obtained with bilateral orchiectomy
* Progressive castration-resistant prostate cancer with two or more skeletal metastases identified by 99mTC bone scintigraphy. One or more lymph node metastases allowed, but not mandatory. Lymph node metastases in each individually must measure less than 3 cm in the longest dimension. Visible visceral organ metastases are not allowed. A diagnosis of prostate cancer must have been histologically confirmed at any time point
* Baseline prostatic specific antigen (PSA) level of 1 ng/mL or higher with evidence of progressively increasing PSA values (two consecutive increases over the previous reference value)
* Progression after at least one of the following: abiraterone, enzalutamide, apalutamide, darolutamide, or taxane chemotherapy (docetaxel, cabazitaxel). There is no maximum number of prior therapies. Prior immunotherapies (for example, Sipuleucel-T or pembrolizumab) do not exclude the patient from participation
* Age \>= 18 years. Castrate-resistant prostate cancer (CRPC) affects older adults and is rarely encountered in children and adolescents
* Life expectancy \>= 6 months
* Albumin \> 2.5 mg/dL
* Hemoglobin \> 9 g/dL
* Leukocytes \>= 3,000/mcL
* Absolute neutrophil count \>= 1,500/mcL
* Platelets \>= 100,000/mcL
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (with the exception of \< 3 mg/dL for patients with Gilbert's disease)
* Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN
* Creatinine =\< 1.5 x institutional ULN OR
* Glomerular filtration rate (GFR) \>= 40 mL/min/1.73 m\^2
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy (with no medications prohibited by this protocol \[e.g. drug-drug interactions\]) with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy (with no medications prohibited by this protocol \[e.g. drug-drug interactions\]), if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load (with no medications prohibited by this protocol \[e.g. drug-drug interactions\])
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional classification. To be eligible for this trial, patients should be class 2B or better
* Concomitant use of physiologic corticosteroids is allowed
* Concomitant use of bisphosphonates is allowed (use of bone health agents is mandatory - either denosumab \[preferred\] or bisphosphonates)
* The effects of radium-223 dichloride, M3814, and avelumab on the developing human fetus are unknown. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of Radium-223 dichloride, M3814, and avelumab administration
* Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible
* Patients must be able to swallow orally administered medication
* Patients with asymptomatic, treated brain metastases are permitted if there is no evidence of progression for at least 4 weeks after central nervous system (CNS)-directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging \[MRI\] or CT scan) during the screening period
Exclusion Criteria:
* Active autoimmune conditions or patients on chronic immunosuppression due to underlying autoimmune condition
* Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
* Patients who are receiving any other investigational agents
* Patients who have had previous hemibody external radiation
* Patients who have had systemic radiotherapy with radioisotopes
* Patients who have imminent/established spinal cord compression, pathological fracture in weight bearing bones or bone lesion with soft tissue component unless treated as appropriate with radiation and/or surgery before starting on trial
* Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to radium-223 dichloride, M3814, or avelumab
* Patients unable to discontinue medications or substances that are potent inhibitors, inducers or sensitive substrates of CYP3A4/5 or CYP2C19 prior to study treatment are ineligible.
* Medications or substances that are strong inhibitors of CYP3A4/5 or CYP2C19 must be discontinued at least 1 week prior to first M3814 dose.
* Medications or substances that are strong inducers of CYP3A4/5 or CYP2C19 must be stopped at least 3 weeks prior to the first M3814 dose.
* Drugs mainly metabolized by CYP3A with a narrow therapeutic index (as judged by the Investigator or authorized designee) must be discontinued at least 1 day prior to first M3814 dose.
* Note: Because the lists of these agents are constantly changing, it is important to regularly consult a frequently- updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the- counter medicine or herbal product.
* Radium-223 dichloride should not be given concurrently with abiraterone plus prednisone/prednisolone
* Patients with uncontrolled intercurrent illness
* Patients with psychiatric illness/social situations that would limit compliance with study requirements
* Patients must not have an active infection requiring systemic treatment
* Patients must not use immunosuppressive medication =\< 7 days of registration, EXCEPT for the following:
* Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)
* Systemic corticosteroids at physiologic doses =\< 10 mg/day of prednisone or equivalent
* Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
* Patients who cannot discontinue concomitant H2 blockers or proton-pump inhibitors (PPIs). Patients may confer with the study doctor to determine if such medications can be discontinued. These must be discontinued \>= 5 days prior to study treatment. Patients do not need to discontinue calcium carbonate
* Patients receiving sorivudine or any chemically related analogues (such as brivudine) are excluded
* Patients with a known history or present osteonecrosis of the jaw DRUG: Avelumab, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, DRUG: Peposertib, OTHER: Questionnaire Administration, RADIATION: Radium Ra 223 Dichloride
Metastatic Castration-Resistant Prostate Carcinoma, Metastatic Malignant Neoplasm in the Bone, Metastatic Malignant Neoplasm in the Lymph Nodes, Stage IV Prostate Cancer AJCC v8, Prostate
UT Southwestern
Best Available Therapy Versus Autologous Hematopoetic Stem Cell Transplant for Multiple Sclerosis (BEAT-MS) (BEAT-MS)
This is a multi-center prospective rater-masked (blinded) randomized controlled trial of 156 participants, comparing the treatment strategy of Autologous Hematopoietic Stem Cell Transplantation (AHSCT) to the treatment strategy of Best Available Therapy (BAT) for treatment-resistant relapsing multiple sclerosis (MS). Participants will be randomized at a 1 to 1 (1:1) ratio. All participants will be followed for 72 months after randomization (Day 0, Visit 0).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Manuel.Huichapa@UTSouthwestern.edu
Benjamin Greenberg
ALL
18 Years to 55 Years old
PHASE3
NCT04047628
STU-2020-0855
Inclusion Criteria:
• Age 18 to 55 years, inclusive, at the time of the screening Visit -2.
• Diagnosis of MS according to the 2017 McDonald Criteria139.
• EDSS ≤ 6.0 at the time of randomization (Day 0).
• T2 abnormalities on brain MRI that fulfill the 2017 McDonald MRI criteria for dissemination in space139. A detailed MRI report or MRI images must be available for review by the site neurology investigator.
• Highly active treatment-resistant relapsing MS, defined as ≥ 2 episodes of disease activity in the 36 months prior to the screening visit (Visit -2). The two disease activity episodes will be a clinical MS relapse or MRI evidence of MS disease activity and must meet all the criteria described below:
• At least one episode of disease activity must occur following ≥ 1 month of treatment with one of the following: (i) an oral DMT approved by the FDA for the treatment of relapsing MS, or (ii) a monoclonal antibody approved by the FDA for the treatment of relapsing MS, or (iii) rituximab. Qualifying DMTs include: dimethyl fumarate, diroximel fumarate, monomethyl fumarate, teriflunomide, cladribine, daclizumab, ponesimod, siponimod, ozanimod, fingolimod, rituximab, ocrelizumab, natalizumab, alemtuzumab, ublituximab, and ofatumumab, and
• At least one episode of disease activity must have occurred within the 12 months prior to the screening visit (Visit -2), and
• At least one episode of disease activity must be a clinical MS relapse (see item c.i. below). The other episode(s) must occur at least one month before or after the onset of the clinical MS relapse, and must be either another clinical MS relapse or MRI evidence of disease activity (see item c.ii. below): i. Clinical MS relapse must be confirmed by a neurologist's assessment and documented contemporaneously in the medical record. If the clinical MS relapse is not documented in the medical record, it must be approved by the study adjudication committee (see Section 3.5), and ii. MRI evidence of disease activity must include ≥ 1 unique active lesion on one or more brain or spinal cord MRIs. Detailed MRI reports or MRI images must be available for review by the site neurology investigator. A unique active lesion is defined as either of the following:
• A gadolinium-enhancing lesion, or 2. A new non-enhancing T2 lesion compared to a reference scan obtained not more than 36 months prior to the screening visit (Visit -2).
• Candidacy for treatment with at least one of the following high efficacy BAT DMTs: cladribine, natalizumab, alemtuzumab, ocrelizumab, ofatumumab, ublituximab and rituximab. Candidacy for treatment for each BAT DMT is defined as meeting all of the following:
• No prior disease activity episode, as defined in Inclusion Criterion #5, with the candidate BAT DMT, and
• No contraindication to the candidate BAT DMT, and
• No treatment with the candidate BAT DMT in the 12 months prior to screening.
• Completion of COVID-19 vaccination series, according to the current Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) recommendations, ≥ 14 days prior to randomization (Day 0).
• Positive for VZV antibodies, or completion of at least one dose of the varicella zoster glycoprotein E (gE) Shingrix vaccine at least 4 weeks prior to randomization (Day 0).
• Insurance approval for MS treatment with at least one candidate BAT DMT (see Inclusion Criterion #6).
• Ability to comply with study procedures and provide informed consent, in the opinion of the investigator.
• Females of childbearing potential (defined in Section 5.4.3.1) and males with female partners of childbearing potential are required to adhere to the contraception provisions of Section 5.4.3.1.
• For participants who use medicinal or recreational marijuana, willingness to substitute MARINOL® if randomized to AHSCT (Section 5.4.2.6).
Exclusion Criteria:
• Diagnosis of primary progressive MS according to the 2017 McDonald criteria.
• History of neuromyelitis optica spectrum disorder or MOG antibody disease.
• Prior treatment with an investigational agent within 3 months or 5 half-lives, whichever is longer. Agents authorized by the FDA for prevention or treatment of COVID-19 are not considered investigational.
• Either of the following within one month prior to randomization (Day 0):
• Onset of acute MS relapse, or
• Treatment with intravenous methylprednisolone 1000 mg/day for 3 days or equivalent.
• Initiation of any BAT DMT (see Section 5.2.1) between Visit -2 and randomization (Day 0).
• Brain MRI or cerebrospinal fluid (CSF) examination indicating a diagnosis of progressive multifocal leukoencephalopathy (PML).
• History of cytopenia consistent with the diagnosis of myelodysplastic syndrome (MDS).
• Presence of unexplained cytopenia, polycythemia, thrombocythemia or leukocytosis.
• History of sickle cell anemia or other hemoglobinopathy.
• Evidence of past or current hepatitis B or hepatitis C infection, including treated hepatitis B or hepatitis C. Hepatitis B surface antibody following hepatitis B immunization is not considered to be evidence of past infection.
• Presence or history of mild to severe cirrhosis.
• Hepatic disease with the presence of either of the following:
• Total bilirubin ≥ 1.5 times the upper limit of normal (ULN) or total bilirubin ≥ 3.0 times the ULN in the presence of Gilbert's syndrome, or
• Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) ≥ 2.0 times the ULN.
• Positive COVID-19 PCR test, or alternative nucleic acid amplification test (NAAT) per institutional standards, within 14 days prior to randomization (Day 0).
• Evidence of HIV infection.
• Positive QuantiFERON - TB Gold,TB Gold Plus, or T-SPOT®.TB test results. PPD tuberculin test may be substituted for QuantiFERON - TB Gold, TB Gold Plus, or T-SPOT®.TB test.
• Active viral, bacterial, endoparasitic, or opportunistic infections.
• Active invasive fungal infection.
• Hospitalization for treatment of infections or parenteral (IV or IM) antibacterials, antivirals, antifungals, or antiparasitic agents within the 30 days prior to randomization (Day 0) unless clearance is obtained from an Infectious Disease specialist.
• Receipt of live or live-attenuated vaccines within 6 weeks of randomization (Day 0).
• Presence or history of clinically significant cardiac disease including: a. Arrhythmia requiring treatment with any antiarrhythmia therapy, with the exception of low dose beta blocker for intermittent premature ventricular contractions. b. Coronary artery disease with a documented diagnosis of either: i. Chronic exertional angina, or ii. Signs or symptoms of congestive heart failure. c. Evidence of heart valve disease, including any of the following: i. Moderate to severe valve stenosis or insufficiency, or ii. Symptomatic mitral valve prolapse, or iii. Presence of prosthetic mitral or aortic valve.
• Left ventricular ejection fraction (LVEF) \< 50%.
• Impaired renal function defined as eGFR \< 60 mL/min/1.73 m2, according to the CKD-EPI formula144.
• Forced expiratory volume in one second (FEV1) \< 70% predicted (no bronchodilator).
• Diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected for Hgb) \< 70% predicted.
• Poorly controlled diabetes mellitus, defined as HbA1c \> 8%.
• History of malignancy, except adequately treated localized basal cell or squamous skin cancer, or carcinoma in situ of the cervix. Malignancies for which the participant is judged to be cured will be considered on an individual basis by the study adjudication committee (see Section 3.5).
• Presence or history of any moderate to severe rheumatologic autoimmune disease requiring treatment, including but not limited to the following: systemic lupus erythematous, systemic sclerosis, rheumatoid arthritis, Sjogren's syndrome, polymyositis, dermatomyositis, mixed connective tissue disease, polymyalgia rheumatica, polychondritis, sarcoidosis, vasculitis syndromes, or unspecified collagen vascular disease.
• Presence of active peptic ulcer disease, defined as endoscopic or radiologic diagnosis of gastric or duodenal ulcer.
• Prior history of AHSCT.
• Prior history of solid organ transplantation.
• Positive pregnancy test or breastfeeding.
• Failure to willingly accept or comprehend irreversible sterility as a side effect of therapy.
• Psychiatric illness, mental deficiency, or cognitive dysfunction severe enough to interfere with compliance or informed consent.
• History of hypersensitivity to rabbit or Escherichia coli-derived proteins.
• Any metallic material or electronic device in the body, or other condition that precludes the participant from undergoing MRI with gadolinium administration, as determined by the site radiologist.
• Presence or history of ischemic cerebrovascular disorders, including but not limited to transient ischemic attack, subarachnoid hemorrhage, cerebral thrombosis, cerebral embolism, or cerebral hemorrhage.
• Presence or history of other neurological disorders, including but not limited to CNS or spinal cord tumor; metabolic or infectious cause of myelopathy; genetically-inherited progressive CNS disorder; CNS sarcoidosis; or systemic autoimmune disorders potentially causing progressive neurologic disease or affecting ability to perform the study assessments.
• Presence of any medical comorbidity that the investigator determines will significantly increase the risk of treatment mortality.
• Presence of any other concomitant medical condition that the investigator deems incompatible with trial participation.
PROCEDURE: Autologous Hematopoietic Stem Cell Transplantation, BIOLOGICAL: Best Available Therapy (BAT)
Relapsing Multiple Sclerosis, Relapsing Remitting Multiple Sclerosis, Secondary Progressive Multiple Sclerosis
Treatment-Resistant Relapsing Multiple Sclerosis (MS), Autologous Hematopoietic Stem Cell Transplantation (AHSCT), Autologous Peripheral Blood Stem Cells (PBMCs) Graft, Best Available Therapy (BAT), Disease-Modifying Therapy (DMT), BAT DMT
UT Southwestern
Suicide Treatment Alternatives for Teens (START)
Quasi-Randomized trial to compare inpatient care versus outpatient crisis intervention clinic. This study plans to enroll up to 1,000 participants across 4 sites in a 5 years period.
Call 214-648-5005
studyfinder@utsouthwestern.edu, AMY.CONGER@UTSouthwestern.edu
Graham Emslie
ALL
12 Years to 18 Years old
NA
NCT04089254
STU-2023-0203
Inclusion Criteria:
• Adolescents that are 12 through 17 years old (including 17 year olds who will turn 18 years old during the course of the study).
• Are brought to the Emergency Department (ED) due to suicidal thoughts or behaviors
• Require a higher level of care (OCIC or Inpatient) indicated by clinician determination and a CHRT-SR score of 15 to 52.
• The presence of a legal guardian
• Capable of giving signed informed consent/assent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion Criteria:
• Adolescents with suicidal thoughts that place themselves at a serious imminent risk of suicide based on clinical judgment.
• Adolescents who require 24 hour/day supervision but no adult can provide 24 hour/day supervision outside of the hospital
• Adolescents without the ability to read and answer survey questions
• Adolescents that are non-English speaking due to the scales and surveys that are used for this study only being available in English.
BEHAVIORAL: Inpatient Psychiatry, BEHAVIORAL: Outpatient Crisis Intervention Clinic
Suicidal Ideation, Psychiatric Disorders
Suicide, Suicidal, Adolescent
Children’s Health
A Study of E7386 in Combination With Other Anticancer Drug in Participants With Solid Tumor
The primary objective of this study is to assess the safety and tolerability and to determine the recommended Phase 2 dose (RP2D) of E7386 in combination with other anticancer drug(s).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Miller
All
18 Years and over
Phase 1
NCT04008797
STU-2023-0509
Inclusion Criteria:
• HCC part only: Participants with confirmed diagnosis of unresectable HCC with any of the following criteria:
• Histologically or cytologically confirmed diagnosis of HCC, excluding fibrolamellar, sarcomatoid or mixed cholangio-HCC tumors
• Clinically confirmed diagnosis of HCC according to American Association for the Study of Liver Diseases (AASLD) criteria, including cirrhosis of any etiology and/or chronic hepatitis B or C infection ST part only (except for HCC): Participants with histologically or cytologically confirmed diagnosis of solid tumor for which no alternative standard therapy or no effective therapy exists
• Life expectancy of >=12 weeks
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
• All AEs due to previous anti-cancer therapy have either returned to Grade 0 to 1 except for alopecia or up to Grade 2 peripheral neuropathy (renal/bone marrow/liver function should meet the inclusion criteria)
• Adequate washout period before study drug administration:
• Chemotherapy and radiotherapy: 3 weeks or 5 times the half-life, whichever is shorter
• Any antitumor therapy with antibody: 4 weeks or more
• Any investigational drug or device: 4 weeks or more
• Blood/platelet transfusion or granulocyte colony-stimulating factor (G-CSF): 2 weeks or more Note: Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not had radiation pneumonitis
• Adequate controlled blood pressure (BP), renal function, bone marrow function, liver function, and serum mineral level
• At least one measurable lesion based on mRECIST (for HCC Subparts in Dose Escalation Part) or on RECIST 1.1 (for Other ST Subparts in Dose Escalation Part and all subparts in Expansion Part) meeting following criteria
• At least 1 lesion of >=1.0 centimeter (cm) in the longest diameter for a non-lymph node or >=1.5 cm in the short-axis diameter for a lymph node that is serially measurable according to RECIST 1.1 using computerized tomography (CT)/magnetic resonance imaging (MRI)
• Lesions that have had external beam radiotherapy or loco-regional therapies such as radiofrequency ablation, or transarterial chemoembolisation (TACE)/ transarterial embolization (TAE) must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion
• For HCC participants only: Child-Pugh score A. Note: If Child-Pugh score 7 or more was observed during Screening or Baseline, the participant is ineligible and re-assessment of the Child-Pugh score is not permitted.
• For HCC participants only: Participants categorized to stage B (not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment), or stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system
• For HCC Subpart in Expansion Part only: prior systemic therapy for locally advanced or metastatic disease is as defined below a. Participants who have received only one prior line of immuno oncology (IO) based regimen and have progressed on or after prior treatment with IO based regimen, or IO ineligible participants who have received no prior systemic therapy. Participants who previously received lenvatinib treatment are ineligible
• For CRC Subpart in Expansion Part only: participants must have received at least 2 prior regimens (not exceeding 4 prior regimens) or could not tolerate standard treatment and must have received the following prior therapies in the metastatic setting if approved and locally available (progressed on at least 1 prior regimen in the metastatic setting or could not tolerate standard treatment): Note: Adjuvant chemotherapy counts as prior systemic treatment if there is documented disease progression within 6 months of treatment completion Note: If a participant is determined to be intolerant to prior standard treatment, the participant must have received at least of 2 cycles of that therapy Note: Participants who have received oral tyrosine kinase inhibitor (example, regorafenib) are ineligible
• Fluoropyrimidine, irinotecan and oxaliplatin with or without an anti-Vascular endothelial growth factor (VEGF) monoclonal antibody (mAb) (example, bevacizumab). Note: Capecitabine is acceptable as equivalent to fluoropyrimidine in prior treatment Note: Participants who have previously received fluoropyrimidine, oxaliplatin, and irinotecan as part of the same and only chemotherapy regimen, example, FOLFOXIRI or FOLFIRINOX, may be eligible after discussion with the Sponsor
• Chemotherapy with anti- epidermal growth factor receptor (EGFR) mAb (cetuximab or panitumumab) for participants with rat sarcoma virus (RAS) (Kirsten rat sarcoma viral oncogene homolog [KRAS)/ NRAS]) wild type (WT) CRC Note: RAS (KRAS/NRAS) WT participants with right or left CRC lesions who may have not been treated with anti-EGFR mAb based on local guidelines are eligible
• BRAF inhibitor (in combination with cetuximab ± binimetinib) for BRAF V600E mutated tumors
• Immune checkpoint inhibitor for participants with microsatellite instability-high (MSI-H) CRC
• For EC Subpart in Expansion Part only: Participants who have radiographic evidence of disease progression after prior systemic therapies. Participants must have received platinum-based chemotherapy regimen and IO based regimen (example, lenvatinib + pembrolizumab or pembrolizumab monotherapy) for EC. Participants may have received up to 1 additional line of platinum-based chemotherapy if given in the neoadjuvant or adjuvant treatment setting, but not exceeding 3 lines of therapies. If participants are ineligible for IO therapy, participants who have received only 1 prior systemic therapy including platinum based chemotherapy regimen are eligible Note: There is no restriction regarding prior hormonal therapy
Exclusion Criteria:
• Any of cardiac conditions as follows:
• Heart failure New York Heart Association (NYHA) Class II or above
• Unstable ischaemic heart disease (myocardial infarction within 6 months prior to starting study drug, or angina requiring use of nitrates more than once weekly)
• Prolongation of QT interval with Fridericias correction (QTcF) to greater than (>) 480 millisecond (msec)
• Left ventricular ejection fraction (LVEF) less than 50 percent (%)
• Major surgery within 21 days or minor surgery (that is, simple excision) within 7 days prior to starting study drug. Participant must have recovered from the surgery related toxicities to less than Grade 2. Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility
• Known to be human immunodeficiency virus (HIV) positive Note: the sponsor has evaluated whether to include participant with HIV. Given that this is the first combination study of E7386 with lenvatinib and that the main mechanism of action of E7386 is immunomodulation of the tumor microenvironment along with the fact that several anti-retroviral therapies have drug-drug interaction with cytochrome P450 3A (CYP3A) substrates, the sponsor has decided not to include these participants at the current time. However, further considerations will be made moving forward based on new emerging data Note: HIV testing is required at screening only when mandated by local health authority
• Participants with proteinuria >1 positive on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with urine protein >=1 gram per 24 hour will be ineligible
• Active infection requiring systemic treatment (Except for Hepatitis B and/or C [HBV/HCV] infection in HCC participants) In case of HBsAg (+) participants in HCC participants:
• Antiviral therapy for HBV is not ongoing
• HBV viral load is 2000 international unit per milliliter (IU/mL) or more at the Screening Period although antiviral therapy for HBV is ongoing
• Has dual active HBV infection (HBsAg (+) and/or detectable HBV deoxyribonucleic acid [DNA]) and HCV infection (anti-HCV Ab (+) and detectable HCV ribonucleic acid [RNA]) at study entry
• Diagnosed with meningeal carcinomatosis
• Participants with central nervous system metastases are only eligible if they have been previously treated and are radiologically stable, (that is, without evidence of progression for at least 4 weeks prior to first dose of study treatment by repeat imaging), clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen
• Any of bone disease/conditions as follows:
• Osteoporosis with T-score of < minus (-) 3.0 at the left or right total hip, left or right femoral neck or lumbar spine (L1-L4) as determined by dual energy x-ray absorptiometry (DXA) scan. Participants with T-score <-2.5 to -3.0 and no prior medical therapy for osteoporosis can only be included if treatment with a bisphosphonate (example, zoledronic acid) or denosumab has been started at least 14 days prior to the first dose of study drug
• Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia
• Symptomatic hypercalcemia requiring bisphosphonate therapy
• History of any fracture within 6 months prior to starting study drug
• Bone metastasis requiring orthopedic intervention
• Bone metastasis not being treated by bisphosphonate or denosumab. Participants may be included if treatment with bisphosphonate or denosumab has been started at least 14 days prior to the first dose of study drug. Participants with previous solitary bone lesions controlled with radiotherapy are eligible.
• History of symptomatic vertebral fragility fracture or any fragility fracture of the hip, pelvis, wrist or other location (defined as any fracture without a history of trauma or because of a fall from standing height or less)
• Moderate (25% to 40% decrease in the height of any vertebrae) or severe (>40% decrease in the height of any vertebrae) morphometric vertebral fracture at baseline
• History of malignancy (except for original disease, or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, carcinoma in-situ [example, bladder or cervix]) within the past 24 months prior to the first dose of study drug
• For HCC Subpart in Dose Escalation Part only: Participants who experienced discontinuation of lenvatinib, 2 or more multiple dose reductions of lenvatinib required from initial dose level of this study due to its toxicity, or participants who experienced single dose reduction or consecutive >=8 days dose interruption of lenvatinib within 60 days from the first dose, due to its toxicity. EC Subpart in Expansion Part only: Participants previously treated with lenvatinib who experienced discontinuation of lenvatinib due to toxicity, or dose reduction to less than 14 mg of lenvatinib due to toxicity
• Bleeding or thrombotic disorders or use of anticoagulants requiring therapeutic International Normalized Ratio (INR) monitoring for HCC participants only (example, warfarin or similar agents). Treatment with low molecular weight heparin and factor X inhibitors is permitted. Treatment with antiplatelet agents is prohibited for HCC participants in Dose Escalation Part only
• Gastrointestinal bleeding event or active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug
• For HCC participants only: History of hepatic encephalopathy within 6 months prior to starting study drug
• For EC Subpart in Expansion Part only: carcinosarcoma (malignant mixed Mullerian tumor), endometrial leiomyosarcoma, and endometrial stromal sarcomas
• Has preexisting >=Grade 3 gastrointestinal or non-gastrointestinal fistula
• Evidence of current COVID-19 infection or ongoing unrecovered active sequelae of COVID-19 infection
• Males who have not had a successful vasectomy (confirmed azoospermia) if their female partners meet the exclusion criteria above (that is, the female partners are of childbearing potential and are not willing to use a highly effective contraceptive method throughout the study period and for 90 days after study drug discontinuation). No sperm donation is allowed during the study period and for 90 days after study drug discontinuation
• Has a known psychiatric or substance abuse disorder that would interfere with the participant ability to cooperate with the requirements of the study
• Evidence of clinically significant disease (example, cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator could affect the participant safety or interfere with the study assessments
• Scheduled for major surgery during the study
Drug: E7386, Drug: Lenvatinib
Neoplasms, Carcinoma, Hepatocellular, Liver Neoplasms, Colorectal Neoplasms, Endometrial Neoplasms, Corpus Uteri, Colon, Liver
Solid Tumor, Hepatocellular carcinoma, Endometrial cancer, Colorectal cancer, E7386, Lenvatinib
UT Southwestern
89Zr-DFO-Atezolizumab ImmunoPET/CT in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma
This is an exploratory clinical trial to assess the potential of 89Zr-DFO-Atezolizumab Positron Emission Tomography/Computed Tomography (PET/CT) scans in patients with locally advanced or metastatic renal cell carcinoma (RCC). This open label, nontherapeutic trial will test the correlation of 89Zr-DFO-Atezolizumab immunoPET/CT with programmed death-ligand 1 (PD-L1) expression and the response to immune checkpoint inhibitor therapy in patients with RCC. There will be two cohorts, one made up of patients with localized RCC who will undergo 89Zr-DFO-Atezolizumab PET/CT prior to nephrectomy and a second cohort of patients with metastatic RCC who will undergo 89Zr-DFO-Atezolizumab PET/CT prior to treatment with an immune checkpoint inhibitor.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
James Brugarolas
ALL
18 Years and over
PHASE2
NCT04006522
STU-2019-0714
Inclusion Criteria:
* Patients with suspected renal cell carcinoma with planned surgery or patients with metastatic RCC and a tissue diagnosis. (In standard clinical practice, biopsy is not routinely performed in patients who will be having surgery).
* Ability to understand and the willingness to sign a written informed consent.
* Patient must be able to lie still for a 30 to 60 minute PET/CT scan.
* One of the following:
• Patients with locally advanced RCC planned for surgery determined to be a high risk of recurrence, defined by presence of at least clinical T2 or TxN1, OR patients with metastatic RCC for whom treatment with cytoreductive nephrectomy and/or metastasectomy is planned by the treating physician.
• Patients with metastatic RCC for whom immuno-oncology (IO) therapy is planned. * Women of child-bearing potential must agree to undergo and have documented a negative pregnancy test on the day of 89Zr-DFO-Atezolizumab administration. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
Exclusion Criteria:
* History of severe allergic, anaphylactic, or other hypersensitivity reactions to atezolizumab or any other chimeric or humanized antibodies.
* Uncontrolled severe and irreversible intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements.
* Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
* Significant autoimmune disease requiring treatment with either prednisone (or steroid equivalent) at a dose \> 10 mg/day or other immunosuppressive agents. (Replacement steroid therapy is acceptable).
* Any patient for whom ICI therapy would be contraindicated for other reasons. Patients with adverse reactions to ICI therapy may undergo second 89Zr-DFO-Atezolizumab injection and PET/CT at the discretion of the treating physician considering that the dose of antibody represents 1% of a single therapeutic dose and therefore unlikely to cause adverse events.
* Subjects unable to provide informed consent.
* Subjects who are claustrophobic or have other contraindications to PET/CT.
* Subjects must not weigh more than the maximum weight limit for the table for the PET/CT scanner where the study is being performed. (\>200 kg or 440 lbs). DRUG: 89Zr-DFO-Atezolizumab, PROCEDURE: Positron Emission Tomography/Computed Tomography
Renal Cell Carcinoma, Kidney
renal cell carcinoma, atezolizumab, PET/CT
UT Southwestern; Parkland Health & Hospital System
A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma (GBM AGILE)
Glioblastoma (GBM) adaptive, global, innovative learning environment (GBM AGILE) is an international, seamless Phase II/III response adaptive randomization platform trial designed to evaluate multiple therapies in newly diagnosed (ND) and recurrent GBM.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Michael Youssef
ALL
18 Years and over
PHASE2
NCT03970447
STU-2019-1281
Newly Diagnosed
Inclusion Criteria:
* Age ≥ 18 years.
* Histologically confirmed Grade IV GBM, inclusive of gliosarcoma (WHO criteria; IDH wild-type by immunohistochemistry \[IHC\] or sequencing for IDH) established following either a surgical resection or biopsy. An MRI scan with the required imaging sequences performed within 21 days prior to randomization preferably. The post-operative MRI scan performed within 96 hours of surgery or the MRI scan performed for radiation therapy planning may serve as the MRI scan performed during screening if all required imaging sequences were obtained.
* Karnofsky performance status ≥ 60% performed within a 14-day window prior to randomization.
* Availability of tumor tissue representative of GBM from definitive surgery or biopsy.
Recurrent Inclusion Criteria:
* Age ≥ 18 years.
* Histologically confirmed Grade IV GBM, inclusive of gliosarcoma (WHO criteria; IDH wild-type by immunohistochemistry \[IHC\] or sequencing for IDH) at first or second recurrence after initial standard, control or experimental therapy that includes at a minimum radiation therapy (RT).
* Evidence of recurrent disease demonstrated by disease progression using slightly modified Response Assessment in Neuro-Oncology (RANO) criteria.
* Two scans to confirm progression are required: at least 1 scan at the time of progression and 1 scan prior to the time of progression.
* Karnofsky performance status ≥ 70% performed within a 14-day window prior to randomization.
* Availability of tumor tissue representative of GBM from initial definitive surgery and/or, recurrent surgery, if performed.
Newly Diagnosed Exclusion Criteria:
* Received any prior treatment for glioma including: a. Prior prolifeprospan 20 with carmustine wafer. b. Prior intracerebral, intratumoral, or cerebral spinal fluid (CSF) agent. c. Prior radiation treatment for GBM or lower-grade glioma. d. Prior chemotherapy or immunotherapy for GBM or lower-grade glioma. Receiving additional, concurrent, active therapy for GBM outside of the trial.
* Extensive leptomeningeal disease.
* QTc \> 450 msec if male and QTc \> 470 msec if female.
* History of another malignancy in the previous 2 years, with a disease-free interval of \< 2 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.
Recurrent Exclusion Criteria:
* Early disease progression prior to 3 months (12 weeks) from the completion of RT.
* More than 2 prior lines for chemotherapy administration. (NOTE: In the 1st line adjuvant setting, combination of temozolomide (TMZ) with an experimental agent, is considered one line of chemotherapy.)
* Received any prior treatment with lomustine, agents part of any of the experimental arms, and bevacizumab or other vascular endothelial growth factor (VEGF) or VEGF receptor-mediated targeted agent.
* Any prior treatment with prolifeprospan 20 with carmustine wafer.
* Any prior treatment with an intracerebral agent.
* Receiving additional, concurrent, active therapy for GBM outside of the trial
* Extensive leptomeningeal disease.
* QTc \> 450 msec if male and QTc \> 470 msec if female.
* History of another malignancy in the previous 2 years, with a disease-free interval of \< 2 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. DRUG: Temozolomide, DRUG: Lomustine, DRUG: Regorafenib, RADIATION: Radiation, DRUG: Paxalisib, DRUG: VAL-083, DRUG: VT1021, DRUG: Troriluzole, BIOLOGICAL: ADI-PEG 20
Glioblastoma, Brain and Nervous System
Glioblastoma, Newly diagnosed, recurrent, O6-methylguanine-DNA-methyltransferase (MGMT) methylated, MGMT unmethylated, isocitrate dehydrogenase (IDH) wild-type, Bayesian, adaptive randomization, Master Protocol, Platform Trial, Phase 2, Phase 3
UT Southwestern