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221 Study Matches
Efficacy and Safety of Zanidatamab With Standard-of-care Therapy Against Standard-of-care Therapy for Advanced HER2-positive Biliary Tract Cancer
The purpose of this study is to evaluate the efficacy and safety of Zanidatamab plus CisGem (Cisplatin and Gemcitabine) with or without the addition of a programmed death protein 1/ligand-1 (PD-1/L1) inhibitor (physician's choice of either Durvalumab or Pembrolizumab, where approved under local regulations) as first line of treatment for participants with human epidermal growth factor receptor 2 (HER2)-positive biliary tract cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Hsieh
ALL
18 Years to old
PHASE3
NCT06282575
STU-2024-0655
Inclusion Criteria
• Histologically- or cytologically-confirmed Biliary Tract Cancer (BTC), including Gallbladder Cancer (GBC), Intrahepatic Cholangiocarcinoma (ICC), or Extrahepatic Cholangiocarcinoma (ECC).
• Locally advanced unresectable or metastatic BTC and not eligible for curative resection, transplantation, or ablative therapies.
• Received no more than 2 cycles of systemic therapy which is limited to Cisplatin and Gemcitabine (CisGem) with or without a PD-1/L1 inhibitor (physician's choice of durvalumab or pembrolizumab, where approved under local regulations) for advanced unresectable or metastatic disease.
• HER2-positive disease (defined as IHC 3+; or IHC 2+/ ISH+) by IHC and in situ Hybridization (ISH) assay (in participants with IHC 2+ tumors) at a central laboratory on new biopsy tissue or archival tissue from the most recent biopsy.
• Assessable (measurable or non-measurable) disease as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), per investigator assessment.
• Male or female ≥ 18 years or age (or the legal age of adulthood per country-specific regulations).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function
• Females of childbearing potential must have a negative pregnancy test result.
• Females of childbearing potential and males with a partner of childbearing potential must be willing to use 2 methods of birth control. Exclusion Criteria
• Prior treatment with a HER2-targeted agent
• Prior treatment with checkpoint inhibitors, other than durvalumab or pembrolizumab
• The following BTC histologic subtypes are excluded: small cell cancer, neuroendocrine tumors, lymphoma, sarcoma, mixed tumor histology, and mucinous cystic neoplasms detected in the biliary tract region.
• Use of systemic corticosteroids.
• Brain metastases
• Severe chronic or active infections
• History of allogeneic organ transplantation.
• Active or prior autoimmune inflammatory conditions
• History of interstitial lung disease or non-infectious pneumonitis.
• Participation in another clinical trial with an investigational medicinal product within the last 3 months.
• Females who are breastfeeding
• Any other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures.
• Use of phenytoin
• Histologically- or cytologically-confirmed Biliary Tract Cancer (BTC), including Gallbladder Cancer (GBC), Intrahepatic Cholangiocarcinoma (ICC), or Extrahepatic Cholangiocarcinoma (ECC).
• Locally advanced unresectable or metastatic BTC and not eligible for curative resection, transplantation, or ablative therapies.
• Received no more than 2 cycles of systemic therapy which is limited to Cisplatin and Gemcitabine (CisGem) with or without a PD-1/L1 inhibitor (physician's choice of durvalumab or pembrolizumab, where approved under local regulations) for advanced unresectable or metastatic disease.
• HER2-positive disease (defined as IHC 3+; or IHC 2+/ ISH+) by IHC and in situ Hybridization (ISH) assay (in participants with IHC 2+ tumors) at a central laboratory on new biopsy tissue or archival tissue from the most recent biopsy.
• Assessable (measurable or non-measurable) disease as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), per investigator assessment.
• Male or female ≥ 18 years or age (or the legal age of adulthood per country-specific regulations).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function
• Females of childbearing potential must have a negative pregnancy test result.
• Females of childbearing potential and males with a partner of childbearing potential must be willing to use 2 methods of birth control. Exclusion Criteria
• Prior treatment with a HER2-targeted agent
• Prior treatment with checkpoint inhibitors, other than durvalumab or pembrolizumab
• The following BTC histologic subtypes are excluded: small cell cancer, neuroendocrine tumors, lymphoma, sarcoma, mixed tumor histology, and mucinous cystic neoplasms detected in the biliary tract region.
• Use of systemic corticosteroids.
• Brain metastases
• Severe chronic or active infections
• History of allogeneic organ transplantation.
• Active or prior autoimmune inflammatory conditions
• History of interstitial lung disease or non-infectious pneumonitis.
• Participation in another clinical trial with an investigational medicinal product within the last 3 months.
• Females who are breastfeeding
• Any other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures.
• Use of phenytoin
DRUG: Zanidatamab, DRUG: Cisplatin, DRUG: Gemcitabine, DRUG: Pembrolizumab, DRUG: Durvalumab
Biliary Tract Cancer, Other Digestive Organ
JZP598, ZW25, HER-2 positive BIliary Tract cancer, Gallbladder Cancer, Intrahepatic Cholangiocarcinoma (ICC), Extrahepatic Cholangiocarcinoma (ECC), Zanidatamab, HER-2 overexpression, HER-2 amplification
UT Southwestern
Study of Pembrolizumab and Lenvatinib in Metastatic and Recurrent Cervix Cancer (LenPem Cervix)
The main purpose of this study is to gather information about an investigational drug combination, Lenvatinib in combination with pembrolizumab, that may help to treat cervical cancers. In this study, we are looking to see whether the combination of lenvatinib and pembrolizumab has any effect on slowing tumor growth in cervical cancer tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Jayanthi Lea
FEMALE
18 Years and over
PHASE2
NCT06266338
STU-2023-1118
Inclusion Criteria:
Participants are eligible to be included in the study only if all the following criteria apply:
• Female participants who are at least 18 years of age on the day of signing informed consent.
• Histologically confirmed diagnosis of squamous, adenocarcinoma or adenosquamous cervical cancer, that is recurrent or metastatic.
• Prior therapy: May have received up to 2 prior lines of systemic chemotherapy in the setting of advanced, metastatic (Stage IVB) or recurrent cervical cancer. May have received prior checkpoint inhibitor for advanced, metastatic (Stage IVB) or recurrent cervical cancer. May have received prior bevacizumab or antiangiogenic agent for recurrent or metastatic cervical cancer,
• Include whether prior checkpoint inhibitor was used in first line setting or second line setting.
• Prior Radiation therapy will be allowed and not counted as a line of treatment.
• Prior chemotherapy used as radiation sensitizer (e.g. cisplatin) used as treatment during chemoradiation will be allowed and counted as a line of treatment.
• Female participants: * A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: * Not a woman of childbearing potential (WOCBP) OR Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days post pembrolizumab or 30 days post lenvatinib whichever occurs last. The investigator should evaluate the potential for contraceptive method failure (i.e., noncompliance, recently initiated) in relationship to the first dose of study intervention. * A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention. * If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. * The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
• Participants must have a PD-L1 diagnostic test of primary or recurrent archival tumor tissue.
• Participants may have progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all the following criteria:
• Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
• Has demonstrated disease progression after anti-PD-1/L1 as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment no less than 4 weeks from the date of the first documented disease progression, in the absence of rapid clinical progression.
• Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb. i. Progressive disease is determined according to iRECIST. ii. This determination is made by the investigator. Once disease progression is confirmed, the initial date of disease progression documentation will be considered the date of disease progression.
• Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy are eligible.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Archival tumor tissue sample or newly obtained \[core, incisional or excisional\] biopsy of a tumor lesion not previously irradiated has been provided. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
• Have an Eastern Cooperative Oncology Group performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
• Have adequate organ and marrow function as defined in the following table (Table 2). Specimens must be collected within 10 days prior to the start of study intervention.
• Criteria for known Hepatitis B and C positive subjects. Hepatitis B and C screening tests are not required unless: * Known history of HBV or HCV infection * As mandated by local health authority
• Hepatitis B positive subjects * Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization. * Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.
• Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening.
• Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization.
• Have adequately controlled BP with or without antihypertensive medications, defined as BP ≤150/90 mmHg with no change in antihypertensive medications within 1 week prior to randomization.
• Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
• A WOCBP who has a positive urine pregnancy test within 72 hours prior to enrollment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
• Has received prior systemic anti-cancer therapy including investigational agents within 2 weeks prior to allocation.
• Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids. Note: 2 weeks or fewer of palliative radiotherapy for non-CNS disease, with a 1-week washout, is permitted.
• Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed. Note: please refer to Section 4.9 for information on COVID-19 vaccines.
• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within seven days prior to the first dose of study drug.
• Known additional malignancy that is progressing or has required active treatment within the past five years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid)
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.
• Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV testing is required unless mandated by local health authority.
• Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection. Note: Hepatitis B and C screening tests are not required unless: * Known history of HBV and HCV infection * As mandated by local health authority
• Has had major surgery within three weeks prior to first dose of study interventions. Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
• Has had an allogenic tissue/solid organ transplant.
• Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula.
• Has urine protein ≥1 g/24 hours. Note: Participants with proteinuria ≥2+ (≥100 mg/dL) on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria.
• Has a LVEF below the institutional (or local laboratory) normal range, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO).
• Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation. Note: The degree of proximity to major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy
• Prolongation of QTcF interval to \>480 ms.
• Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. Note: Medically controlled arrhythmia would be permitted.
• Gastrointestinal malabsorption or any other condition that might affect the absorption of Lenvatinib.
• Active hemoptysis (bright red blood of at least 0.5 teaspoon) within three weeks prior to the first dose of study drug.
DRUG: Pembrolizumab, DRUG: Lenvatinib
Cervix Cancer, Cervical Cancer, Cervix
UT Southwestern; Parkland Health & Hospital System
VO and Nivolumab vs Physician's Choice in Advanced Melanoma That Progressed on Anti-PD-1 & Anti-CTLA-4 Drugs [IGNYTE-3]
This is a randomized, controlled, multicenter, open-label Phase 3 clinical study comparing VO in combination with nivolumab versus Physician's Choice treatment for patients with unresectable Stage IIIb-IV cutaneous melanoma whose disease progressed on an anti PD-1 and an anti-CTLA-4 containing regimen (administered either as a combination regimen or in sequence) or who are not candidates for treatment with an anti-CTLA-4 therapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Wang
ALL
12 Years to old
PHASE3
NCT06264180
STU-2024-0547
Key
• Treatment with prior anti-PD-1 therapy must have continued for a minimum of 8 weeks (note: treatment with prior pembrolizumab therapy when administered every 6 weeks must have continued for a minimum of 12 weeks \[ie, 2 treatment cycles\]). Any number of doses of prior anti-CTLA-4 therapy may have been administered in combination with an anti-PD-1. The anti-PD-1-containing therapy must be the immediate prior line of treatment before randomization (for patients with BRAF mutation, see I 4).
• Patients who in the physician's judgement are not candidates for treatment with an anti-CTLA-4 antibody (eg, due to documented clinically significant comorbidities or history of immune-related adverse events) are eligible for the study if they have confirmed PD on an anti-PD-1 antibody (including unresectable disease relapse during adjuvant therapy or \< 6 months from completion of adjuvant therapy).
• Disease progression must have been confirmed and documented using clinical or radiological assessment by 2 assessments at least 4 weeks apart while being treated with an anti-PD-1 antibody and an anti-CTLA-4 antibody. Radiological confirmation of PD can occur during the Screening period for this study. Treatment with prior anti-PD-1 therapy must have continued from the time of initial tumor progression until confirmation of PD (ie, such that no doses of anti-PD-1 therapy were missed). Note: If radiographic progression at the initial scan where PD was documented is accompanied by clear clinical progression, defined as a decline in performance status directly attributed to disease or increased disease-related symptoms, anti-PD-1 therapy does not need to continue. For patients with documented PD while on adjuvant therapy with an anti-PD-1 therapy, a confirmatory biopsy can be used in place of a confirmatory scan. I 4. Has documented BRAF V600 mutation status or must consent to BRAF V600 mutation testing per local institutional standards during the Screening period. Patients with BRAF mutation should have received prior BRAF-directed therapy (with or without a MEK inhibitor) prior to randomization, unless deemed not clinically indicated at Investigator's discretion due to concurrent medical condition or prior toxicity. Note: Prior exposure to BRAF-directed therapy (with or without a MEK inhibitor) includes treatment in the adjuvant setting. One line of BRAF-directed therapy (with or without a MEK inhibitor) can be the most recent systemic treatment administered before randomization. I 5. Has least 1 measurable tumor of ≥ 1 cm in longest diameter (or shortest diameter for lymph nodes) and injectable lesion(s) of at least 1 cm in longest diameter. I 6. Has adequate hematologic function, including:
• White blood cell (WBC) count ≥ 2.0 × 109/L
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
• Platelet count ≥ 75 × 109/L
• Hemoglobin ≥ 8 g/dL (without packed red blood cell \[RBC\] transfusion within 2 weeks of dosing) I 7. Has adequate hepatic function, including:
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN; \< 2.0 × ULN for patients with known Gilbert syndrome or liver metastases)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 × ULN (or ≤ 5.0 × ULN, if liver metastases are present)
• Alkaline phosphatase (ALP) ≤ 2.5 × ULN (or ≤ 5.0 × ULN, if liver or bone metastases are present) I 8. Has adequate renal function, defined as serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 3 0 mL/minute/1.73 m2 (measured using Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula). I 9. Prothrombin time (PT) ≤ 1.5 × ULN (or international normalization ratio \[INR\] ≤ 1.3) and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. Note: Patients who are on chronic anticoagulant therapy may be randomized if the target INR is ≤ 2.5. For patients requiring deep injection of VO, the INR must be \<1.5 at the time of injection. I 10. ECOG performance status (PS) 0 to 1 for patients 18 and older or a Lansky PS ≥ 80 for patients 12 to 17 years of age. I 11. Life expectancy of at least 3 months. I 12. Female and male patients of reproductive potential must agree to avoid becoming pregnant or impregnating a partner and adhere to highly effective contraception requirements during the treatment period and for at least 6 months after the last dose of any study treatment. I 13. Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) test with a minimum sensitivity of 25 IU/L or equivalent units or β hCG within 7 days before the first dose of study treatment. I 14. Capable of giving signed informed consent which includes willingness to comply with the requirements and restrictions listed in the informed consent form (ICF) Key
Inclusion Criteria:
I 1. Male or female who is 12 years of age or older at the time of signed informed consent.
I 2. Patients with histologically or cytologically confirmed unresectable or metastatic Stage IIIb through IV/M1a through M1d cutaneous melanoma, as per AJCC staging system, 8th edition).
I 3. Confirmed disease progression (PD) on an anti-PD-1 antibody treatment and an anti-CTLA-4 antibody treatment, administered as either a combination regimen (eg, nivolumab + ipilimumab) or in sequence.
• Treatment with prior anti-PD-1 therapy must have continued for a minimum of 8 weeks (note: treatment with prior pembrolizumab therapy when administered every 6 weeks must have continued for a minimum of 12 weeks \[ie, 2 treatment cycles\]). Any number of doses of prior anti-CTLA-4 therapy may have been administered in combination with an anti-PD-1. The anti-PD-1-containing therapy must be the immediate prior line of treatment before randomization (for patients with BRAF mutation, see I 4).
• Patients who in the physician's judgement are not candidates for treatment with an anti-CTLA-4 antibody (eg, due to documented clinically significant comorbidities or history of immune-related adverse events) are eligible for the study if they have confirmed PD on an anti-PD-1 antibody (including unresectable disease relapse during adjuvant therapy or \< 6 months from completion of adjuvant therapy).
• Disease progression must have been confirmed and documented using clinical or radiological assessment by 2 assessments at least 4 weeks apart while being treated with an anti-PD-1 antibody and an anti-CTLA-4 antibody. Radiological confirmation of PD can occur during the Screening period for this study. Treatment with prior anti-PD-1 therapy must have continued from the time of initial tumor progression until confirmation of PD (ie, such that no doses of anti-PD-1 therapy were missed). Note: If radiographic progression at the initial scan where PD was documented is accompanied by clear clinical progression, defined as a decline in performance status directly attributed to disease or increased disease-related symptoms, anti-PD-1 therapy does not need to continue. For patients with documented PD while on adjuvant therapy with an anti-PD-1 therapy, a confirmatory biopsy can be used in place of a confirmatory scan. I 4. Has documented BRAF V600 mutation status or must consent to BRAF V600 mutation testing per local institutional standards during the Screening period. Patients with BRAF mutation should have received prior BRAF-directed therapy (with or without a MEK inhibitor) prior to randomization, unless deemed not clinically indicated at Investigator's discretion due to concurrent medical condition or prior toxicity. Note: Prior exposure to BRAF-directed therapy (with or without a MEK inhibitor) includes treatment in the adjuvant setting. One line of BRAF-directed therapy (with or without a MEK inhibitor) can be the most recent systemic treatment administered before randomization. I 5. Has least 1 measurable tumor of ≥ 1 cm in longest diameter (or shortest diameter for lymph nodes) and injectable lesion(s) of at least 1 cm in longest diameter. I 6. Has adequate hematologic function, including:
• White blood cell (WBC) count ≥ 2.0 × 109/L
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
• Platelet count ≥ 75 × 109/L
• Hemoglobin ≥ 8 g/dL (without packed red blood cell \[RBC\] transfusion within 2 weeks of dosing) I 7. Has adequate hepatic function, including:
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN; \< 2.0 × ULN for patients with known Gilbert syndrome or liver metastases)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 × ULN (or ≤ 5.0 × ULN, if liver metastases are present)
• Alkaline phosphatase (ALP) ≤ 2.5 × ULN (or ≤ 5.0 × ULN, if liver or bone metastases are present) I 8. Has adequate renal function, defined as serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 3 0 mL/minute/1.73 m2 (measured using Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula). I 9. Prothrombin time (PT) ≤ 1.5 × ULN (or international normalization ratio \[INR\] ≤ 1.3) and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. Note: Patients who are on chronic anticoagulant therapy may be randomized if the target INR is ≤ 2.5. For patients requiring deep injection of VO, the INR must be \<1.5 at the time of injection. I 10. ECOG performance status (PS) 0 to 1 for patients 18 and older or a Lansky PS ≥ 80 for patients 12 to 17 years of age. I 11. Life expectancy of at least 3 months. I 12. Female and male patients of reproductive potential must agree to avoid becoming pregnant or impregnating a partner and adhere to highly effective contraception requirements during the treatment period and for at least 6 months after the last dose of any study treatment. I 13. Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) test with a minimum sensitivity of 25 IU/L or equivalent units or β hCG within 7 days before the first dose of study treatment. I 14. Capable of giving signed informed consent which includes willingness to comply with the requirements and restrictions listed in the informed consent form (ICF) Key
Exclusion Criteria:
E 1. Primary mucosal or uveal melanoma. E 2. More than 2 lines of systemic therapy for advanced melanoma. Note: One additional line of anti-PD-1 therapy in the adjuvant or neoadjuvant setting is allowed if the patient was free of treatment and of PD for at least 6 months and subsequently had confirmed PD on an anti-PD-1 and an anti-CTLA-4 antibody therapy administered in the advanced setting.
E 3. Known acute or chronic hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known acute or chronic hepatitis C virus (defined as HCV RNA \[qualitative\] is detected).
Note: Patients who have been effectively treated are eligible for randomization. Patients must be negative for HBsAg and HCV RNA.
E 4. Known human immunodeficiency virus (HIV) infection. Note: Testing for HIV is not required unless mandated by local health authority or clinically indicated.
E 5. Active significant herpetic infections or prior complications of HSV-1 infection (eg, herpetic keratitis or encephalitis) or requires intermittent or chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (eg, acyclovir).
Note: Patients with sporadic cold sores may be randomized if no active cold sores are present at the time of first dose of study treatment.
E 6. Had systemic infection requiring IV antibiotics or other serious active infection requiring antimicrobial, antiviral, or antifungal treatment within 14 days prior to the first dose.
E 7. Evidence of spinal cord compression or at high risk of spinal cord compression.
E 8. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis at time of screening. Patients with known central nervous system metastases are eligible if they have received standard-of-care therapy for central nervous system disease (such as stereotactic radiosurgery or radical surgical resection followed by radiotherapy) and have evidence of disease stability on 2 subsequent scans performed at least at a 4-week interval.
E 9. Serum lactate dehydrogenase (LDH) \> 2 × ULN. E 10. Major surgery ≤ 2 weeks prior to starting study treatment. Note: Patients must have recovered adequately from all acute complications of all previous procedures prior to randomization.
E 11. Prior malignancy active within the previous 3 years, except for locally curable cancers that have apparently been cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ (without invasive component) of the prostate, cervix, or breast.
E 12. History of significant cardiac disease including myocarditis or congestive heart failure (defined as New York Heart Association Functional Classification III or IV), or unstable angina, serious uncontrolled cardiac arrhythmia, cerebral vascular accident, or myocardial infarction within 6 months from first dose of VO.
E 13. History of life-threatening toxicity related to prior immune therapy except those that are unlikely to recur with standard countermeasures (eg, hormone replacement after adrenal crisis).
E 14. History or evidence of psychiatric, substance abuse (including IV substance abuse), or any other clinically significant disorder, condition, or disease (with the exception of those described above) that, in the opinion of the Investigator or the Medical Monitor, would pose a risk to patient safety or interfere with the study evaluation, procedures, or completion.
E 15. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
E 16. Active, known, or suspected autoimmune disease requiring systemic treatment.
E 17. History of (noninfectious) pneumonitis that required steroids or has current pneumonitis.
E 18. Prior oncolytic virus therapy or other therapy given by intratumoral administration.
E 19. Requires chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (eg, acyclovir).
E 20. Has received a live vaccine within 28 days prior to the first dose of study treatment.
E 21. Systemic anticancer therapies within 5 half-lives or 4 weeks of the first dose, whichever is shorter.
E 22. Is currently participating in or has participated in a study of an investigational agent within 4 weeks prior to the first dose of study treatment.
E 23. Has received prior radiotherapy within 2 weeks of start of study treatment or has not recovered from radiotherapy.
E 24. Conditions requiring treatment with immunosuppressive doses (\> 10 mg per day of prednisone or equivalent) of systemic corticosteroids other than for corticosteroid replacement therapy 14 days before randomization.
Note: Patients who require a brief course (≤ 7 days) or corticosteroids (eg, as prophylaxis for imaging studies due to hypersensitivity to contrast agents) are not excluded. Physiologic replacement doses of systemic corticosteroids are permitted, only if the dose does not exceed 10 mg/day prednisone equivalent.
E 25. History of allergy or sensitivity to study drug components (VO, nivolumab, pembrolizumab, or relatlimab) or to cisplatin or carboplatin or paclitaxel (dependent on cohort) or prior monoclonal antibody treatment.
E 26. Treatment with botanical preparations (eg, herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to treatment.
E 27. Is a person who is deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily. BIOLOGICAL: Vusolimogene Oderparepvec, BIOLOGICAL: Nivolumab, BIOLOGICAL: Nivolumab + Relatlimab, BIOLOGICAL: Pembrolizumab, DRUG: Single-agent chemotherapy
Advanced Melanoma, Melanoma, skin
UT Southwestern
A Study of Valemetostat Tosylate in Combination With DXd ADCs in Subjects With Solid Tumors
This study will evaluate the safety, tolerability, and efficacy of valemetostat tosylate in combination with DXd ADC in patients with advanced solid tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Timothy Brown
ALL
18 Years to old
PHASE1
NCT06244485
STU20240005
Key Inclusion Criteria
All participants must meet all of the following criteria, as well as all criteria from the relevant sub-protocol to be eligible for enrollment:
* At least 18 years or the minimum legal adult age (whichever is greater) at the time the ICF is signed.
* Has at least 1 measurable lesion based on investigator imaging assessment (computed tomography or magnetic resonance imaging) using RECIST v 1.1 at Screening.
* Is willing to provide an adequate tumor sample.
* Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at Screening.
Additional Key Inclusion for Sub-Protocol A:
* Diagnosed with pathologically documented breast cancer that:
• Is unresectable or metastatic.
• Has progressed on and would no longer benefit from endocrine therapy in hormone receptor-positive subjects in the opinion of the investigator.
• Has been treated with at least 1 and at most 2 prior lines of chemotherapy in the recurrent or metastatic setting.
• Has a history of low HER2 expression, defined as IHC 2+ /ISH-negative or IHC 1+ (ISH-negative or untested). ), as classified by the American Society of Clinical Oncology/College of American Pathologists 2018 HER2 testing guidelines.
• Was never previously HER2-positive (IHC 3+ or IHC 2+/ISH+) on prior pathology testing (per American Society of Clinical Oncology/College of American Pathologists guidelines Additional Key Inclusion for Sub-Protocol B: • Gastric or GEJ adenocarcinoma that is (a) unresectable or metastatic or (b) has progressed on trastuzumab or approved trastuzumab biosimilar-containing regimen. Additional Key Inclusion for Sub-Protocol C: * Pathologically documented Stage IIIB, IIIC, or IV non-squamous NSCLC with or without AGA at the time of enrollment. * Must meet prior therapy requirements: * Participants without AGA: (a) received platinum-based chemotherapy in combination with α-PD-1/α -PD-L1 mAb as a prior line of therapy or (b) received platinum-based chemotherapy and α -PD-1/ α -PD-L1 mAb (in either order) sequentially as 2 prior lines of therapy. * Participants with AGA: (a) has been treated with at least 1 or 2 prior lines of applicable targeted therapy that is locally approved for participant's genomic alteration at the time of Screening, (b) participants who have received platinum-based chemotherapy as a prior line of cytotoxic therapy, (c) may have received α -PD-1/α -PD-L1 mAb alone or in combination with a cytotoxic agent Key Exclusion Criteria * Has previously been treated with any enhancer of zeste homolog inhibitors. * Uncontrolled or significant cardiovascular disease. * Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. * Has leptomeningeal carcinomatosis or metastasis. * Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses. * Current use of moderate or strong cytochrome P450 (CYP)3A inducers. * Systemic treatment with corticosteroids (\>10 mg daily prednisone equivalents). * History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs). * Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection requiring treatment with intravenous (IV) antibiotics, antivirals, or antifungals. * Female who is pregnant or breastfeeding or intends to become pregnant during the study. * Psychological, social, familial, or geographical factors that would prevent regular follow-up. Additional Key Exclusion for Sub-Protocol A: * Has previously received any anti-HER2 therapy in the metastatic setting. * Has received prior treatment with an antibody-drug conjugate that consists of an exatecan derivative that is a topoisomerase I inhibitor, including either as part of prior treatment history or within prior participation in a clinical study. Additional Key Exclusion for Sub-Protocol B: \* Participants who have received an antibody-drug conjugate consisting of an exatecan derivative that is a topoisomerase I inhibitor. Additional Key Exclusion for Sub-Protocol C: \* Has received any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I or TROP2-targeted therapy including Dato-DXD
• Is unresectable or metastatic.
• Has progressed on and would no longer benefit from endocrine therapy in hormone receptor-positive subjects in the opinion of the investigator.
• Has been treated with at least 1 and at most 2 prior lines of chemotherapy in the recurrent or metastatic setting.
• Has a history of low HER2 expression, defined as IHC 2+ /ISH-negative or IHC 1+ (ISH-negative or untested). ), as classified by the American Society of Clinical Oncology/College of American Pathologists 2018 HER2 testing guidelines.
• Was never previously HER2-positive (IHC 3+ or IHC 2+/ISH+) on prior pathology testing (per American Society of Clinical Oncology/College of American Pathologists guidelines Additional Key Inclusion for Sub-Protocol B: • Gastric or GEJ adenocarcinoma that is (a) unresectable or metastatic or (b) has progressed on trastuzumab or approved trastuzumab biosimilar-containing regimen. Additional Key Inclusion for Sub-Protocol C: * Pathologically documented Stage IIIB, IIIC, or IV non-squamous NSCLC with or without AGA at the time of enrollment. * Must meet prior therapy requirements: * Participants without AGA: (a) received platinum-based chemotherapy in combination with α-PD-1/α -PD-L1 mAb as a prior line of therapy or (b) received platinum-based chemotherapy and α -PD-1/ α -PD-L1 mAb (in either order) sequentially as 2 prior lines of therapy. * Participants with AGA: (a) has been treated with at least 1 or 2 prior lines of applicable targeted therapy that is locally approved for participant's genomic alteration at the time of Screening, (b) participants who have received platinum-based chemotherapy as a prior line of cytotoxic therapy, (c) may have received α -PD-1/α -PD-L1 mAb alone or in combination with a cytotoxic agent Key Exclusion Criteria * Has previously been treated with any enhancer of zeste homolog inhibitors. * Uncontrolled or significant cardiovascular disease. * Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. * Has leptomeningeal carcinomatosis or metastasis. * Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses. * Current use of moderate or strong cytochrome P450 (CYP)3A inducers. * Systemic treatment with corticosteroids (\>10 mg daily prednisone equivalents). * History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs). * Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection requiring treatment with intravenous (IV) antibiotics, antivirals, or antifungals. * Female who is pregnant or breastfeeding or intends to become pregnant during the study. * Psychological, social, familial, or geographical factors that would prevent regular follow-up. Additional Key Exclusion for Sub-Protocol A: * Has previously received any anti-HER2 therapy in the metastatic setting. * Has received prior treatment with an antibody-drug conjugate that consists of an exatecan derivative that is a topoisomerase I inhibitor, including either as part of prior treatment history or within prior participation in a clinical study. Additional Key Exclusion for Sub-Protocol B: \* Participants who have received an antibody-drug conjugate consisting of an exatecan derivative that is a topoisomerase I inhibitor. Additional Key Exclusion for Sub-Protocol C: \* Has received any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I or TROP2-targeted therapy including Dato-DXD
DRUG: Valemetostat tosylate, DRUG: T-DXd, DRUG: Dato-DXd
Advanced Solid Tumor, Breast - Female, Breast - Male, Lung/Thoracic, Other
Advanced Solid Tumor, Valemetostat tosylate, DXD Antibody-drug Conjugates
UT Southwestern
A Study of LY4101174 in Participants With Recurrent, Advanced or Metastatic Solid Tumors (EXCEED)
The purpose of this study is to find out whether the study drug, LY4101174, is safe, tolerable and effective in participants with select advanced or metastatic solid tumors. The study is conducted in two parts - phase Ia (dose-escalation, dose-optimization) and phase Ib (dose-expansion). The study will last up to approximately 4 years.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years and over
PHASE1
NCT06238479
STU-2024-0162
Inclusion Criteria:
* Have one of the following solid tumor cancers:
* Cohort A1: urothelial carcinoma, triple negative breast cancer, non-small cell lung cancer, esophageal cancer, pancreatic cancer, ovarian cancer, cervical cancer (squamous cell carcinoma), head and neck squamous cell carcinoma or prostate cancer
* Cohort A2/B1/B2: urothelial carcinoma
* Cohort C1: triple negative breast cancer
* Cohort C2: non-small cell lung cancer
* Cohort C3: ovarian or fallopian tube cancer
* Cohort C4: cervical cancer
* Cohort C5: head and neck squamous cell carcinoma
* Prior Systemic Therapy Criteria:
* Cohort A1/C1-5: Individual has received all standard therapies for which the participant was deemed to be an appropriate candidate by the treating investigator; OR there is no standard therapy available for the disease. There is no restriction on number of prior therapies
* Cohort A2/B1/B2: Individual must have received at least one prior regimen in the advanced or metastatic setting. There is no restriction on number of prior therapies.
* Prior enfortumab vedotin specific requirements:
* Cohorts A1/A2/C1-5: prior treatment with enfortumab vedotin is allowed, but not required
* Cohort B1: individual must be enfortumab vedotin naive in the advanced/metastatic setting
* Cohort B2: individual must have received enfortumab vedotin in the metastatic/advanced setting.
* Measurability of disease
* Cohort A1: measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST 1.1)
* Cohorts A2, B1, B2, C1-5: measurable disease required as defined by RECIST v1.1
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Have adequate archival tumor tissue sample available or undergo a screening biopsy if allowed per country specific regulations
Exclusion Criteria:
* Individual with known or suspected uncontrolled CNS metastases
* Individual with uncontrolled hypercalcemia
* Individual with uncontrolled diabetes
* Individual with evidence of corneal keratopathy or history of corneal transplant
* Any serious unresolved toxicities from prior therapy
* Significant cardiovascular disease
* Current of history of intestinal obstruction in the previous 3 months
* Recent thromboembolic event and/or clinically significant bleeding
* Prolongation of QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 ms
* History of pneumonitis/interstitial lung disease
* History of Grade ≥3 skin toxicity when receiving enfortumab vedotin
* Individuals who are pregnant, breastfeeding or plan to breastfeed during study or within 30 days of last dose of study intervention
* Individual with active uncontrolled infection DRUG: LY4101174
Metastatic Solid Tumor, Recurrent Solid Tumor, Advanced Solid Tumor, Urinary Bladder Neoplasm, Triple Negative Breast Cancer, Non-Small Cell Lung Cancer, Esophageal Cancer, Pancreatic Cancer, Ovarian Cancer, Cervical Cancer, Head and Neck Squamous Cell Carcinoma, Prostate Cancer, Renal Pelvis Cancer, Bladder Cancer, Breast - Female, Breast - Male, Cervix, Esophagus, Larynx, Lip, Oral Cavity and Pharynx, Lung/Thoracic, Ovary, Pancreas, Prostate, Urinary Bladder
Bladder Cancer, Bladder Neoplasm, Bladder Urothelial Carcinoma, Urinary Bladder Cancer, Urinary Tract Cancer, Urothelial Neoplasms, Renal Pelvis Cancer, Ureter Cancer, Nectin-4, Antibody Drug Conjugate (ADC)
UT Southwestern
A Study Comparing Talquetamab Plus Pomalidomide, Talquetamab Plus Teclistamab, and Elotuzumab, Pomalidomide, and Dexamethasone or Pomalidomide, Bortezomib, and Dexamethasone in Participants With Relapsed or Refractory Myeloma Who Have Received an Anti-CD38 Antibody and Lenalidomide (MonumenTAL-6)
The purpose of this study is to compare the effectiveness of either talquetamab plus pomalidomide (Tal-P) or talquetamab plus teclistamab (Tal-Tec) with elotuzumab, pomalidomide, and dexamethasone (EPd) or pomalidomide, bortezomib, and dexamethasone (PVd).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Larry Anderson
ALL
18 Years to old
PHASE3
NCT06208150
STU-2024-0939
Inclusion Criteria:
* Documented multiple myeloma as defined by the criteria below: (a) multiple myeloma diagnosis according to the international myeloma working group (IMWG) diagnostic criteria (b) measurable disease at screening as assessed by central laboratory, defined by any of the following: (i) serum M-protein level greater than or equal to (\>=) 0.5 gram per deciliter (g/dL); or (ii) urine M-protein level \>= 200 milligram (mg) per 24 hours; or (iii) light chain multiple myeloma without measurable M-protein in the serum or the urine: serum immunoglobulin (Ig) free light chain (FLC) \>= 10 milligrams per deciliter (mg/dL) and abnormal serum Ig kappa lambda FLC ratio
* Relapsed or refractory disease as defined below: a) Relapsed disease is defined as an initial response to prior treatment, followed by confirmed progressive disease (PD) by IMWG criteria greater than (\>) 60 days after cessation of treatment. b) Refractory disease is defined as less than (\<) 25 percent (%) reduction in M-protein or confirmed PD by IMWG criteria during previous treatment or less than or equal to (\<=) 60 days after cessation of treatment
* Documented evidence of PD or failure to achieve a minimal response to the last line of therapy based on investigator's determination of response by IMWG criteria on or after their last regimen
* Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 at screening and immediately prior to the start of administration of study treatment
* A participant must agree not to be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of study treatment
Exclusion Criteria:
* Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients
* Stroke, transient ischemic attack, or seizure within 6 months prior to signing informed consent form (ICF)
* Major surgery or had significant traumatic injury within 2 weeks prior to the start of administration of study treatment, or will not have fully recovered from surgery, or has major surgery planned during the time the participant is expected to be treated in the study or within 2 weeks after administration of the last dose of study treatment
* A maximum cumulative dose of corticosteroids of \>=140 mg of prednisone or equivalent within 14-day period before the first dose of study drug
* Known active central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain magnetic resonance imaging (MRI) and lumbar cytology are required DRUG: Talquetamab, DRUG: Pomalidomide, DRUG: Teclistamab, DRUG: Elotuzumab, DRUG: Dexamethasone, DRUG: Bortezomib
Multiple Myeloma
UT Southwestern
LUNAR-2: TTFields With Pembrolizumab + Platinum-based Chemotherapy for Metastatic NSCLC (LUNAR-2)
This study, known as LUNAR-2, aims to investigate the effectiveness and safety of using TTFields, delivered by the NovoTTF-200T device, concomitantly administered with pembrolizumab and platinum-based chemotherapy for patients with advanced non-small cell lung cancer that has spread to other parts of the body. The primary goals of the study are to assess overall survival and progression-free survival. Secondary objectives include analyzing outcomes based on the specific histology (subtype) of the lung cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Sheena Bhalla
ALL
18 Years to old
PHASE3
NCT06216301
STU-2024-0228
Inclusion Criteria
* ≥22 years of age in the USA
≥18 years of age outside of the USA.
* Histologically or cytologically diagnosis of stage 4 (according to Version 8 of the American Joint Committee on Cancer \[AJCC\] criteria) non-squamous or squamous NSCLC.
* Evaluable (measurable or non-measurable) disease in the thorax per RECIST v1.1.
* Have not received prior systemic treatment for their metastatic NSCLC. Subjects who received adjuvant, neoadjuvant chemotherapy or chemoradiotherapy with curative intent for non-metastatic disease are eligible if the therapy was completed at least 12 months prior to the development of metastatic disease.
* ECOG Performance Status (PS) of 0-1.
* Adequate hematologic and end-organ function
o For subjects not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN (unless participant is receiving anticoagulant therapy as long as INR or aPTT is within therapeutic range of intended use of anticoagulants).
* A female participant is eligible to participate if she is not pregnant, not breastfeeding
* If male subject with a female partner(s) of child-bearing potential, must agree to use an effective contraception
* All subjects must sign written informed consent.
Exclusion Criteria:
All individuals meeting any of the following exclusion criteria will be excluded from study participation:
* Mixed small cell and NSCLC histology.
* EGFR sensitizing mutation and/or ALK translocation, and/or ROS1 and/or RET targetable gene rearrangement, and/or METex14 skipping mutation, and/or NTRK1/2 gene fusion and/or BRAF V600 mutations directed therapy is indicated or planned for other targeted therapy, where such testing and therapy is locally approved and available.
* Has received systemic therapy for metastatic disease.
* Had major surgery \<3 weeks prior to randomization
* Received radiation therapy to the lung that is \> 30 Gy within 6 months of randomization.
* Has received prior radiotherapy within 2 weeks of randomization. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
* Is expected to require any other form of antineoplastic therapy while on study.
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Note: Subjects with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
* Has symptomatic Central Nervous System (CNS) metastases and/or carcinomatous meningitis. Subjects with asymptomatic CNS metastases or with previously treated brain metastases may participate provided they were treated before randomization (if applicable) and are neurologically stable and without requirement of steroid treatment for at least 7 days prior to randomization.
* Has active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior randomization. Subjects with asthma that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study.
* Had prior treatment with any other anti-PD-1, or PD-L1 or PD-L2 agent or an antibody or a small molecule targeting other immuno-regulatory receptors or mechanisms in the 12 months prior to randomization.
* Participation in another clinical study with an investigational agent or device during the 4 weeks prior to randomization.
* Concurrent treatment with other experimental treatments for NSCLC while in the study.
* Has a known sensitivity to any component of the planned systemic therapies (pembrolizumab, cisplatin/carboplatin, pemetrexed/paclitaxel/nab-paclitaxel) .
* Pregnant or breastfeeding
* Admitted to an institution by administrative or court order. DEVICE: NovoTTF-200T, DRUG: Pembrolizumab, DRUG: Platinum based chemotherapy
Metastatic Non-Small Cell Lung Cancer, Lung/Thoracic
NSCLC, Metastatic
UT Southwestern
Dinutuximab With Chemotherapy, Surgery and Stem Cell Transplantation for the Treatment of Children With Newly Diagnosed High Risk Neuroblastoma
This phase III trial tests how well the addition of dinutuximab to Induction chemotherapy along with standard of care surgical resection of the primary tumor, radiation, stem cell transplantation, and immunotherapy works for treating children with newly diagnosed high-risk neuroblastoma. Dinutuximab is a monoclonal antibody that binds to a molecule called GD2, which is found on the surface of neuroblastoma cells, but is not present on many healthy or normal cells in the body. When dinutuximab binds to the neuroblastoma cells, it helps signal the immune system to kill the tumor cells. This helps the cells of the immune system kill the cancer cells, this is a type of immunotherapy. When chemotherapy and immunotherapy are given together, during the same treatment cycle, it is called chemoimmunotherapy. This clinical trial randomly assigns patients to receive either standard chemotherapy and surgery or chemoimmunotherapy (chemotherapy plus dinutuximab) and surgery during Induction therapy. Chemotherapy drugs administered during Induction include, cyclophosphamide, topotecan, cisplatin, etoposide, vincristine, and doxorubicin. These drugs 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. Upon completion of 5 cycles of Induction therapy, a disease evaluation is completed to determine how well the treatment worked. If the tumor responds to therapy, patients receive a tandem transplantation with stem cell rescue. If the tumor has little improvement or worsens, patients receive chemoimmunotherapy on Extended Induction. During Extended Induction, dinutuximab is given with irinotecan, temozolomide. Patients with a good response to therapy move on to Consolidation therapy, when very high doses of chemotherapy are given at two separate points to kill any remaining cancer cells. Following, transplant, radiation therapy is given to the site where the cancer originated (primary site) and to any other areas that are still active at the end of Induction. The final stage of therapy is Post-Consolidation. During Post-Consolidation, dinutuximab is given with isotretinoin, with the goal of maintaining the response achieved with the previous therapy. Adding dinutuximab to Induction chemotherapy along with standard of care surgical resection of the primary tumor, radiation, stem cell transplantation, and immunotherapy may be better at treating children with newly diagnosed high-risk neuroblastoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tanya Watt
ALL
to 30 Years old
PHASE3
NCT06172296
STU-2024-0471
Inclusion Criteria:
* Patients must be enrolled on APEC14B1 and have consented to testing through the Molecular Characterization Initiative (MCI), prior to enrollment on ANBL2131
* ≤ 30 years at the time of initial diagnosis with high-risk disease
* \* Must have a diagnosis of neuroblastoma (NBL) or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamines
* Newly diagnosed, high risk neuroblastoma (HRNBL) defined as one of the following:
* Any age with International Neuroblastoma Risk Group (INRG) Stage L2, MS, or M and MYCN amplification
* Age ≥ 547 days and INRG stage M regardless of biologic features (clinical MYCN testing not required prior to enrollment)
* Any age initially diagnosed with INRG Stage L1 MYCN amplified NBL who have progressed to stage M without systemic chemotherapy
* Age ≥ 547 days of age initially diagnosed with INRG Stage L1, L2, or MS who have progressed to stage M without systemic chemotherapy (clinical MYCN testing not required prior to enrollment)
* Patients must have a body surface area (BSA) ≥ 0.25 m\^2
* No prior anti-cancer therapy except as outlined below:
* Patients initially recognized to have high-risk disease treated with topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing, and with consent
* Patients observed or treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high-risk disease but subsequently found to meet the criteria
* Patients who received localized emergency radiation to sites of life threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis
* Human immunodeficiency virus (HIV) -infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* A serum creatinine based on age/sex as follows:
* 1 month to \< 6 months: Male 0.4 mg/dL and female 0.4mg/dL
* 6 months to \< 1 year: Male 0.5 mg/dL and female 0.5 mg/dL
* 1 to \< 2 years: Male 0.6 mg/dL and female 0.6 mg/dL
* 2 to \< 6 years: Male 0.8 mg/dL and female 0.8 mg/dL
* 6 to \< 10 years: Male 1 mg/dL and female 1 mg/dL
* 10 to \< 13 years: Male 1.2 mg/dL and female 1.2 mg/dL
* 13 to \< 16 years: Male 1.5 mg/dL and female 1.4 mg/dL
* ≥ 16 years: Male 1.7 mg/dL and female 1.4 mg/dL
* The threshold creatinine values were derived from the Schwartz formula for estimating glomerular filtration rate (GFR) utilizing child length and stature data published by the Centers for Disease Control (CDC)
* or a 24-hour urine creatinine clearance ≥ 70 mL/min/1.73 m\^2 or
* or a GFR ≥ 70 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method or direct small molecule clearance method (iothalamate or other molecule per institutional standard)
* Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age
* Serum glutamic pyruvic transaminase (SGPT) (Alanine aminotransferase \[ALT\]) ≤ 10 x ULN\*
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* \* Shortening fraction of ≥ 27% by echocardiogram, or
* Ejection fraction of ≥ 50% by echocardiogram or radionuclide angiogram
* Ability to tolerate Peripheral Blood Stem Cell (PBSC) collection:
No known contraindication to PBSC collection. Examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure
Exclusion Criteria:
* Patients who are 365-546 days of age with INRG Stage M and MYCN non-amplified NBL, irrespective of additional biologic features
* Patients ≥ 547 days of age with INRG Stage L2, MYCN non-amplified NBL, regardless of additional biologic features
* Patients with known bone marrow failure syndromes
* Patients on chronic immunosuppressive medications (e.g., tacrolimus, cyclosporine, corticosteroids) for reasons other than prevention/treatment of allergic reactions and adrenal replacement therapy are not eligible. Topical and inhaled corticosteroids are acceptable
* Patients with a primary immunodeficiency syndrome who require ongoing immune globulin replacement therapy
* 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 prior to enrollment 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
* 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 PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, DRUG: Carboplatin, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, BIOLOGICAL: Dinutuximab, DRUG: Doxorubicin, PROCEDURE: Echocardiography Test, DRUG: Etoposide, PROCEDURE: FDG-Positron Emission Tomography and Computed Tomography Scan, PROCEDURE: Hematopoietic Cell Transplantation, DRUG: Irinotecan, DRUG: Isotretinoin, PROCEDURE: Leukapheresis, PROCEDURE: Magnetic Resonance Imaging, DRUG: Melphalan, PROCEDURE: Multigated Acquisition Scan, RADIATION: Radiation Therapy, PROCEDURE: Radionuclide Imaging, OTHER: Survey Administration, DRUG: Temozolomide, DRUG: Thiotepa, DRUG: Topotecan, PROCEDURE: Tumor Resection, DRUG: Vincristine
Ganglioneuroblastoma, Nodular, Neuroblastoma, Brain and Nervous System
Children’s Health
Study of Revumenib, Azacitidine, and Venetoclax in Pediatric and Young Adult Patients With Refractory or Relapsed Acute Myeloid Leukemia
This is a research study to find out if adding a new study drug called revumenib to commonly used chemotherapy drugs is safe and if they have beneficial effects in treating patients with acute myeloid leukemia (AML) or acute leukemia of ambiguous lineage (ALAL) that did not go into remission after treatment (refractory) or has come back after treatment (relapsed), and to determine the total dose of the 3-drug combination of revumenib, azacitidine and venetoclax that can be given safely in participants also taking an anti-fungal drug. Primary Objective * To determine the safety and tolerability of revumenib + azacitidine + venetoclax in pediatric patients with relapsed or refractory AML or ALAL. Secondary Objectives * Describe the rates of complete remission (CR), complete remission with incomplete count recovery (CRi), and overall survival for patients treated with revumenib + azacitidine + venetoclax at the recommended phase 2 dose (RP2D).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kathleen Ludwig
ALL
1 Year to 30 Years old
PHASE1
NCT06177067
STU-2024-0647
Inclusion Criteria:
Participants must have a diagnosis of AML or ALAL and meet the criteria below:
* Refractory leukemia, defined as persistent leukemia after at least two courses of induction chemotherapy, or relapsed leukemia, defined as the re-appearance of leukemia after the achievement of remission. Patients must have ≥5% blasts in the bone marrow as assessed by morphology or ≥1% blasts flow cytometry. However, if an adequate bone marrow sample cannot be obtained (e.g., in a patient with acute megakaryoblastic leukemia with marrow fibrosis), patients may be enrolled if there is unequivocal evidence of leukemia with ≥5% blasts by morphology or ≥1% blasts flow cytometry in the blood.
* Presence of KMT2A rearrangement (KMT2Ar), NUP98 rearrangement (NUP98r), NPM1 mutation or fusion, PICALM::MLLT10, DEK::NUP214, UBTF-TD, KAT6A::CREBBP, or SET::NUP214
* Adequate organ function, defined as total bilirubin \< 1.5 × institutional upper limit of normal for age or normal conjugated bilirubin (for patients with known Gilbert's syndrome, total bilirubin \<3 × the ULN) unless attributed to leukemia, calculated creatinine clearance ≥60 mL/min/1.73 m\^2, and left ventricular ejection fraction ≥ 40%
* QTcF \< 480 msec (average of triplicate)
* Age ≥ 1 year and ≤ 30 years. The upper age limit may be defined by each institution, but may not exceed 30 years.
* Lansky ≥ 60 for patients who are \< 16 years old and Karnofsky ≥ 60% for patients who are \> 16 years old.
* At least 14 days or 5 half-lives (whichever is longer) must have elapsed since the completion of myelosuppressive therapy, with the exception of low-dose therapy used for cytoreduction according to institutional standards, such as hydroxyurea or low-dose cytarabine (up to 200 mg/m\^2/day). In addition, all toxicities must have resolved to grade 1 or less.
* Patients must have a leukocyte count \<25,000 cells/uL. Low-dose therapy, such as hydroxyurea or cytarabine as described above, to achieve this limit is acceptable.
* For patients who have received prior HCT, there can be no evidence of GVHD and greater than 60 days must have elapsed since the HCT, and patients should be off calcineurin inhibitors for at least 28 days prior to the start of protocol therapy. Physiologic prednisone for the treatment of adrenal insufficiency is acceptable..
* Patients must be taking posaconazole or voriconazole, which must be started at least 24 hours prior to the start of therapy.
* Patients of reproductive potential must agree to use effective contraception for the duration of study participation.
* Patients must be able to swallow tablets.
Patients who meet the criteria listed above are eligible for enrollment and treatment on the trial. However, patients in first relapse who are suitable for and willing to receive intensive remission induction therapy should be offered such therapy if deemed appropriate by the treating physician.
Exclusion Criteria:
* Patients who are pregnant or breastfeeding are not eligible.
* Patients with Down syndrome, acute promyelocytic leukemia, juvenile myelomonocytic leukemia, or bone marrow failure syndromes are not eligible.
* Patients with uncontrolled infection are not eligible. Patients with infections that are controlled on concurrent anti-microbial agents are eligible. DRUG: Revumenib, DRUG: Venetoclax, DRUG: Azacitidine, DRUG: intrathecal (IT) chemotherapy, DRUG: Cytarabine, DRUG: Methotrexate
Refractory Acute Myeloid Leukemia, Relapsed Acute Myeloid Leukemia, Acute Leukemia of Ambiguous Lineage, Myeloid and Monocytic Leukemia
Children’s Health
The PLATINUM Trial: Optimizing Chemotherapy for the Second-Line Treatment of Metastatic BRCA1/2 or PALB2-Associated Metastatic Pancreatic Cancer
This phase II/III trial compares the effect of the 3-drug chemotherapy combination of nab-paclitaxel, gemcitabine, plus cisplatin versus the 2-drug chemotherapy combination of nab-paclitaxel plus gemcitabine for the treatment of patients with pancreatic cancer that has spread to other places in the body (metastatic) and a known genetic mutation in the BRCA1, BRCA2, or PALB2 gene.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Salwan Al Mutar
ALL
18 Years to old
PHASE2
NCT06115499
STU-2024-0540
Inclusion Criteria:
* Metastatic pancreatic adenocarcinoma. Adenosquamous carcinoma, squamous carcinoma, acinar cell carcinoma, and carcinoma not otherwise specified are also acceptable
* BRCA1/2 or PALB2 mutation (somatic or germline) identified on any Clinical Laboratory Improvement Amendments (CLIA)-certified gene panel. Mutations must be considered pathogenic or likely pathogenic by a reference database such as ClinVar or OncoKb.org. (Submission of mutation report will be required)
* Measurable disease
* Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment
* Clinical or radiographic progression on first-line FOLFIRINOX (or nanoliposomal irinotecan, fluorouracil, leucovorin, and oxaliplatin \[NALIRIFOX\]) for metastatic disease
* Patients whose front-line chemotherapy was required to be simplified due to toxicity associated with any of the constituent components of FOLFIRINOX/NALIRIFOX (e.g. simplified to leucovorin calcium, fluorouracil, and oxaliplatin \[FOLFOX\], leucovorin calcium, fluorouracil, and irinotecan \[FOLFIRI\], fluorouracil \[5-FU\] \[including capecitabine\]) will be eligible
* Patients with progressive disease while on maintenance PARP inhibitor treatment after FOLFIRINOX (or NALIRIFOX), irrespective of how long ago they received FOLFIRINOX/NALIRIFOX, will also be eligible
* Patients who develop metastatic disease during or within 6 months after completing FOLFIRINOX/NALIRIFOX in either the locally advanced or adjuvant/neoadjuvant settings will be eligible
* Patients may not have received prior cisplatin for their pancreatic cancer in any setting
\* Note: Patients may have previously received gemcitabine +/- nab-paclitaxel for resectable (neoadjuvant/adjuvant) or locally advanced disease if (1) treatment was completed \> 1 year ago and (2) in the opinion of the treating provider, re-treatment with gemcitabine/nab-paclitaxel is appropriate
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky performance status \>= 60)
* Absolute neutrophil count \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Hemoglobin \>= 8.0 g/dL
* Creatinine =\< 1.8 x institutional upper limit of normal (ULN) or calculated creatinine clearance (Calc. CrCl) \> 40 mL/min
* Total bilirubin =\< 2.0 x institutional ULN
\* Any elevated bilirubin should be asymptomatic at enrollment (except for participants with documented Gilbert's syndrome who may only be included if the total bilirubin =\< 3 x ULN or direct bilirubin =\< 1.5 x ULN)
* Aspartate transaminase (AST)/alanine transaminase (ALT) =\< 3 x institutional ULN
\* AST/ALT of =\< 5 x ULN if liver metastases are present
* 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
* Patients with \> grade 2 peripheral sensory neuropathy are not eligible
* 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 treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression for at least 8-weeks.
\* Patients with known, new or progressive brain metastases (active brain metastases) or leptomeningeal disease are ineligible
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load anytime within 6 months prior to registration 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
* Concomitant chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study
* Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment
Exclusion Criteria:
* N/A DRUG: Nab paclitaxel, DRUG: Gemcitabine, DRUG: Cisplatin, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Computed Tomography, PROCEDURE: Biospecimen Collection
Pancreatic Acinar Cell Carcinoma, Pancreatic Adenocarcinoma, Pancreatic Adenosquamous Carcinoma, Pancreatic Carcinoma, Pancreatic Ductal Adenocarcinoma, Pancreatic Squamous Cell Carcinoma, Stage IV Pancreatic Cancer AJCC v8, Pancreas
UT Southwestern; Parkland Health & Hospital System
Chemotherapy Combined With Immunotherapy Versus Immunotherapy Alone for Older Adults With Stage IIIB-IV Lung Cancer, The ACHIEVE Trial
This phase III trial compares the effect of adding chemotherapy to immunotherapy (pembrolizumab) versus immunotherapy alone in treating patients with stage IIIB-IV lung cancer. 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 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 and chemotherapy may help stabilize lung cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Cynthia Wei
ALL
70 Years to old
PHASE3
NCT06096844
STU-2024-0656
Inclusion Criteria:
* STEP 1 REGISTRATION
* Patient must be ≥ 70 years of age
* Patient must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC) with PD-L1 Tumor Proportion Score (TPS) range of 1-49%
* Patient must have Stage IIIB, IIIC or IV disease and not be candidates for combined chemo-radiation. NOTE: Prior chemo-radiation therapy (RT) for stage III with recurrence is allowed
* Patient must have a tumor that is negative for EGFR mutation/ALK translocations or other actionable first line mutations in which patients would receive first-line oral tyrosine kinase inhibitors
* Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 2
* Patient must agree not to father children while on study and for 6 months after the last dose of protocol treatment
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
* Absolute neutrophil count (ANC) ≥ 1,500/uL (obtained within 14 days prior to Step 1 registration)
* Platelets ≥ 75,000/uL (obtained within 14 days prior to Step 1 registration)
* Hemoglobin (Hgb) ≥ 8.0 g/dL (obtained within 14 days prior to Step 1 registration)
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (obtained within 14 days prior to Step 1 registration)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 3.0 × institutional ULN (obtained within 14 days prior to Step 1 registration)
* Creatinine clearance (CrCL) ≥ 45 mL/min (estimated using Cockcroft-Gault method with actual body weight or measured) (obtained within 14 days prior to Step 1 registration)
* Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months of Step 1 registration 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 undetectable HCV viral
* 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
* Patient must be English or Spanish speaking to be eligible for the QOL component of the study
* NOTE: Sites cannot translate the associated GA or QOL forms
* Patient must not have symptomatic central nervous system disease (CNS) metastases. Patients with a clinical history of CNS metastases or cord compression are eligible if they have been definitively treated and are clinically stable for at least 14 days prior to Step 1 registration and off all steroids for at least 24 hours prior to Step 1 registration. Patients with asymptomatic CNS metastases are eligible
* Patient must not have had any prior cytotoxic chemotherapy regimen for metastatic disease. Chemotherapy given in the setting of adjuvant therapy or locally advanced disease is allowed as long as treatment was completed, and they have fully recovered from treatment related adverse events prior to Step 1 registration
* Patient must not have had any prior immunotherapy for metastatic disease. Immunotherapy given in the setting of adjuvant therapy or locally advanced disease is allowed as long as treatment was completed greater than 6 months prior to Step 1 registration
* Patient must not have a history of uncontrolled autoimmune conditions with the following exceptions, which are allowed: alopecia, vitiligo, rheumatoid arthritis, psoriasis/psoriatic arthritis, Hashimoto's thyroiditis, lupus, inflammatory bowel disease
* Patient must not be on immunosuppressive medication, including steroids (if doses exceed the equivalent of prednisone 10 mg daily). Short courses of steroids which are discontinued prior to randomization are acceptable. Patients on inhaled, intranasal and/or topical steroids are eligible
* Patient must have baseline imaging done assessing all measurable or non-measurable sites of disease within 45 days prior to Step 1 registration
* Investigator must declare their intended chemotherapy regimen should their patient be randomized to Arm B (doublet versus\[vs\] singlet)
* STEP 2 RANDOMIZATION
* Patient must have completed the baseline Geriatric Assessment (GA) after Step 1 registration and prior to Step 2 randomization DRUG: Carboplatin, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, DRUG: Nab-paclitaxel, DRUG: Paclitaxel, BIOLOGICAL: Pembrolizumab, DRUG: Pemetrexed, PROCEDURE: Positron Emission Tomography, OTHER: Questionnaire Administration
Advanced Lung Non-Small Cell Carcinoma, Stage IIIB Lung Cancer AJCC v8, Stage IIIC Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8, Lung/Thoracic
UT Southwestern
A Study Evaluating Atezolizumab, With or Without Bevacizumab, in Participants With Unresectable Hepatocellular Carcinoma and Child-Pugh B7 and B8 Cirrhosis (Kirros)
The purpose of this study is to assess the safety of atezolizumab and bevacizumab, or atezolizumab alone, as first-line treatment in participants with unresectable, locally advanced or metastatic hepatocellular carcinoma (HCC) with Child-Pugh B7 or B8 cirrhosis.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Hsieh
ALL
18 Years to old
PHASE2
NCT06096779
STU-2023-1136
General
Inclusion Criteria:
* Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic participants
* Disease that is not amenable to curative surgical and/or locoregional therapies
* No prior systemic treatment (including systemic investigational agents) for locally advanced or metastatic and/or unresectable HCC
* Measurable disease (at least one untreated target lesion) according to RECIST v1.1
* ECOG Performance Status of 0-2 within 7 days prior to initiation of study treatment
* Child-Pugh B7 or B8 cirrhosis at screening and within 7 days prior to study treatment
* Adequate hematologic and end-organ function
* Life expectancy of at least 12 weeks
* Female participants of childbearing potential must be willing to avoid pregnancy and egg donation
* Absolute neutrophil count ≥1.0 x 109/L (≥1000/μL) without granulocyte colony-stimulating factor support
* Platelet count ≥ 50 × 109/L (50,000/μL) without transfusion
* Hemoglobin ≥ 80 g/L (8 g/dL) AST and ALT ≤ 5 × upper limit of normal (ULN)
* Serum bilirubin ≤ 3 × ULN
* Creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault formula)
* Serum albumin ≥ 20 g/L (2.0 g/dL) without transfusion in the prior 3 months
* INR ≤2.3
General Exclusion Criteria:
* Pregnancy or breastfeeding
* Prior treatment with CD137 agonists or immune checkpoint blockade therapies
* Treatment with investigational therapy within 28 days prior to initiation of study treatment
* Treatment with locoregional therapy to liver within 28 days prior to initiation of study treatment, or non-recovery from side effects of any such procedure
* Treatment with systemic immunostimulatory agents
* Treatment with systemic immunosuppressive medication
* Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment
* Inadequately controlled hypertension
* Active or history of autoimmune disease or immune deficiency
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
* Participants who have a known concurrent malignancy that is progressing or requires active treatment, who have not completely recovered from treatment, or who have a significant malignancy history that, in the opinion of the investigator, should preclude participation.
* Participants on preventative hormonal therapies (i.e., tamoxifen and other hormonal inhibitors) are not excluded.
* Known fibrolamellar HCC, sarcomatoid HCC, other rare HCC variant, or mixed cholangiocarcinoma and HCC
* Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
* Prior allogeneic stem cell or solid organ transplantation
* Actively listed for liver transplantation
* Co-infection with hepatitis B virus (HBV) and hepatitis C virus (HCV)
* Untreated or incompletely treated esophageal and/or gastric varices with bleeding or that are at high risk for bleeding
* A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment
* Grade ≥3 hemorrhage or bleeding event within 6 months prior to initiation of study treatment
* Hepatic encephalopathy is allowed if no active symptoms or stable within 3 months of study treatment
* History, planned, or recommended placement of transjugular intrahepatic portosystemic shunt (TIPS) is excluded from Cohort A only. TIPS is acceptable in Cohort B.
* Diagnostic Paracentesis is allowed. Therapeutic Paracentesis within 3 months is an exclusion criteria
* Participants with ascites controlled on diuretics are allowed.
* History of spontaneous bacterial peritonitis within last 12 months DRUG: Atezolizumab, DRUG: Bevacizumab
Hepatocellular Carcinoma, Liver
Cirrhosis, liver cancer, liver tumor, Child-Pugh B, hepatocellular carcinoma, atezolizumab, bevacizumab, Immune Checkpoint Inhibitor, Digestive System Neoplasms, Kirros, ML44719, liver disease, Genentech, Immunotherapy, CPB, CPB 7, CPB 8, Tecentriq, Avastin, HCC, Cirrhotic Liver, Fatty Liver
UT Southwestern; Parkland Health & Hospital System
National Liver Cancer Screening Trial (TRACER)
The National Liver Cancer Screening Trial is an adaptive randomized phase IV Trial comparing ultrasound-based versus biomarker-based screening in 5500 patients with cirrhosis from any etiology or patients with chronic hepatitis B infection. Eligible patients will be randomized in a 1:1 fashion to Arm A using semi-annual ultrasound and AFP-based screening or Arm B using semi-annual screening using GALAD alone. Randomization will be stratified by sex, enrolling site, Child Pugh class (A vs. B), and HCC etiology (viral vs. non-viral). Patients will be recruited from 15 sites (mix of tertiary care and large community health systems) over a 3-year period, and the primary endpoint of the phase IV trial, reduction in late-stage HCC, will be assessed after 5.5 years.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Amit Singal
ALL
18 Years to 85 Years old
PHASE4
NCT06084234
STU-2023-0842
Inclusion Criteria:
Patient must meet all of the following inclusion criteria:
• Adult patients ages 18-85 with cirrhosis from any etiology or with chronic hepatitis B with a PAGE-B score greater than 9 within 12 months of enrollment
• Patient is eligible for HCC surveillance according to treating physician or by the site investigator
• Able to provide informed consent
• Life expectancy \>6 months (after consent) as determined by the treating provider or site investigator
Exclusion Criteria:
Patient will be excluded for any of the following exclusion criteria:
• Child Pugh C cirrhosis
• History or clinical symptoms of hepatocellular carcinoma or cholangiocarcinoma
• History of solid nodule on baseline ultrasound (i.e., lesion 1cm or greater) within 9 months prior to consent without subsequent diagnostic CT/MRI demonstrating benign nature)
• AFP \>20 ng/mL within 6 months prior to consent, in the absence of a contrast-enhanced CT or MRI within 6 months of AFP (before or after) level demonstrating lack of suspicious liver lesions
• Newly diagnosed LR-3 greater than or equal to 1 cm within 6 months prior to consent
• History of LR-4, LR-5, or LR-M on multi-phase CT or contrast-enhanced MRI within 6 months prior to consent
• Presence of another active cancer besides non-melanomatous skin cancer or indolent cancer under active surveillance (e.g., prostate cancer or renal cell carcinoma) within the 2 years prior to consent
• Patient's provider is planning to use MRI- or CT- based surveillance moving forward
• History of a transjugular intrahepatic portosystemic shunt (TIPS)
• History of Fontan associated liver disease or cardiac cirrhosis
• History of solid organ transplantation
• Actively listed for liver transplantation
• Diagnosis of alcohol-associated hepatitis within 3 months prior to consent
• Documented current or continued signs and symptoms of acute Wilson disease (acute liver failure, acute neurological deficits, hemolysis)
• In patients with primary sclerosing cholangitis (PSC): Current active cholangitis within 90 days prior to consent
• Known or documented habitual non-adherence to previous research studies or medical procedures or unwillingness to adhere to protocol (e.g., unwilling to obtain consent or samples)
• In patients living with HIV: CD4+ T cell count less than 100 cells/mm3 within 60 days prior to consent
• Known pregnancy at consent
• Active warfarin use
DIAGNOSTIC_TEST: GALAD, DIAGNOSTIC_TEST: Liver Ultrasound with or without AFP
Carcinoma, Hepatocellular, Liver Cancer, Liver Cirrhosis, Hepatitis B, Liver
Hepatocellular carcinoma surveillance, GALAD, Alpha Fetoprotein
UT Southwestern; Parkland Health & Hospital System
Phase II Randomized Study of Hypofractionated Versus Conventional Radiotherapy (G-FORCE)
To compare the acute tolerance of highly conformal hypofractionated versus conventional radiotherapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Sher
ALL
18 Years and over
NA
NCT06080503
STU-2023-0715
Inclusion Criteria:
• Pathologically-proven diagnosis of squamous cell carcinoma in situ, squamous cell carcinoma, or squamous cell variants (sarcomatoid, verrucous, basaloid, and papillary subtypes) involving the glottic larynx.
• Clinical stage 0-II (AJCC, 8th edition) with direct laryngoscopy showing no evidence of greater than stage II true glottic larynx cancer and PET/CT or CT neck showing no evidence of regional disease.
• Minimum age is 18 years.
• ECOG Performance Status 0-2
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• 1 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).
• Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
• AJCC stage III or stage IV larynx cancer
• Involvement of the arytenoid cartilage beyond the vocal process.
• Prior chemotherapy for treatment of the targeted larynx lesion.
• Synchronous primaries in the head and neck
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation fields.
• Subjects smoking in excess of 1 pack of cigarettes per day.
• Subjects may not be receiving any other investigational agents.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
RADIATION: LT-SABR, RADIATION: IMRT
Laryngeal Carcinoma, Head and Neck
Larynx
UT Southwestern; Parkland Health & Hospital System
A Study of Intismeran Autogene (V940) Plus Pembrolizumab (MK-3475) Versus Placebo Plus Pembrolizumab in Participants With Non-small Cell Lung Cancer (V940-002) (INTerpath-002)
The goal of this study is to evaluate intismeran autogene plus pembrolizumab versus placebo plus pembrolizumab for the adjuvant treatment of margin negative, completely resected Stage II, IIIA, IIIB (with nodal involvement \[N2\]) non-small cell lung cancer (NSCLC). The primary hypothesis is that intismeran autogene plus pembrolizumab is superior to placebo plus pembrolizumab with respect to disease-free survival (DFS) as assessed by the investigator.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Jonathan Dowell
ALL
18 Years to old
PHASE3
NCT06077760
STU-2024-0708
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Has undergone margin negative, completely resected non-small cell lung cancer (NSCLC), and has pathological Stage II, IIIA, IIIB (N2) squamous or nonsquamous tumor, node, metastasis (TNM) staging per American Joint Committee on Cancer (AJCC) Eighth Edition guidelines.
* Has no evidence of disease before randomization.
* Has received at least one dose of adjuvant treatment with standard of care platinum doublet chemotherapy.
* No more than 24 weeks have elapsed between surgical resection of curative intent and the first dose of pembrolizumab.
* Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization.
* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on anti-retroviral therapy (ART).
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Diagnosis of small cell lung cancer (SCLC) or, for mixed tumors, presence of small cell elements, or has a neuroendocrine tumor with large cell components or a sarcomatoid carcinoma.
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
* Received prior neoadjuvant therapy for their current NSCLC diagnosis.
* Received or is a candidate to receive radiotherapy for their current NSCLC diagnosis.
* Received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-PD-ligand 1 (L1), or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor.
* Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
* Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
* Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication.
* Known additional malignancy that is progressing or has required active treatment within the past 5 years.
* Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed.
* History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
* Active infection requiring systemic therapy. BIOLOGICAL: Intismeran autogene, BIOLOGICAL: Pembrolizumab, OTHER: Placebo
Non-Small Cell Lung Cancer, Lung/Thoracic
UT Southwestern
A Study of Alisertib in Patients With Extensive Stage Small Cell Lung Cancer (ALISCA-Lung1)
PUMA-ALI-4201 is a Phase 2 study evaluating alisertib monotherapy in patients with pathologically-confirmed small cell lung cancer (SCLC) following progression on or after treatment with one platinum-based chemotherapy and anti-PD-L1 immunotherapy agent. Up to one additional systemic anti-cancer therapy for SCLC is allowed, for a total of up to two prior lines of therapy. This study is intended to identify the biomarker-defined subgroup(s) that may benefit most from alisertib treatment and to evaluate the efficacy, safety, and pharmacokinetics of alisertib.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Benjamin Drapkin
ALL
18 Years and over
PHASE2
NCT06095505
STU-2023-1222
Inclusion Criteria:
* Aged ≥18 years at signing of informed consent
* Pathologically confirmed SCLC
* Prior treatment with one platinum-based chemotherapy and an anti-PD-L1 immunotherapy. Up to one additional systemic anti-cancer therapy for SCLC is allowed, for a total of up to two prior lines of therapy
Exclusion Criteria:
* Prior treatment with an AURKA specific-targeted or pan-Aurora-targeted agent, including alisertib in any setting
Note: There are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria. DRUG: Alisertib
Small Cell Lung Cancer, Lung/Thoracic
Alisertib, SCLC
UT Southwestern; Parkland Health & Hospital System
Positron Emission Tomography Using 64Cu-SAR-bisPSMA in Participants With High-risk Prostate Cancer Prior to Radical Prostatectomy (CLARIFY)
The aim for this study is to assess the diagnostic performance of 64Cu-SAR-bisPSMA PET to detect regional nodal metastases.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Orhan Oz
MALE
18 Years to old
PHASE3
NCT06056830
STU-2024-0328
Inclusion Criteria:
* At least 18 years of age.
* Signed informed consent.
* Untreated, histologically confirmed adenocarcinoma of the prostate.
* High-risk or greater PC defined by National Comprehensive Cancer Network Guidelines Version 1.202327 (clinical stage ≥T3a, or Grade Group ≥4, or PSA \>20 ng/mL).
* Patients electing to undergo RP with PLND.
Exclusion Criteria:
* Administration of any high energy (\>300 KeV) gamma-emitting radioisotope within 5 physical half-lives prior to Day 1.
* Known or expected hypersensitivity to 64Cu-SAR-bisPSMA or any of its components.
* Patients with known predominant small cell or neuroendocrine PC. DRUG: 64Cu-SAR-bisPSMA
Prostate Cancer, Prostatic Neoplasms, Prostate
UT Southwestern
Phase 2 Study of Combination Tivozanib and Nivolumab in Advanced Non-Clear Cell Renal Cell Carcinoma
To learn if giving tivozanib in combination with nivolumab can help to control advanced nccRCC.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Hans Hammers
ALL
18 Years to old
PHASE2
NCT06053658
STU-2024-0577
Inclusion Criteria:
• Patients with histologically or cytologically confirmed metastatic non-clear cell renal cell carcinoma of papillary, chromophobe, oncocytic neoplasms, unclassified, or not otherwise specified (NOS) as clear cell. Medullary carcinoma of the kidney and collecting duct tumors are NOT allowed
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Up to 1 systemic line of therapy (either monotherapy or combination) including prior immunotherapy (anti-PD1, PD-L1, or CTLA-4) and multi-tyrosine kinase inhibitors in non-metastatic or metastatic setting is allowed. A washout period of 5 half lives or 21 days, whichever one is shorter, will be required for patients that have received previous systemic therapy.
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) Appendix 1 performance status ≤2 (Karnofsky ≥60%).
• Patients must have adequate organ and marrow function as defined below:
• absolute neutrophil count ≥1,000/mcL
• platelets ≥100,000/mcL
• total bilirubin ≤ institutional upper limit of normal (ULN)
• AST ≤3 × institutional ULN
• (ALT) ≤3 × institutional ULN
• creatinine ≤1.5 × institutional ULN
• eGFR ≥30 ml/min
• 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.
• 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 treated brain metastases (at least 4 weeks have passed from treatment) are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
• Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of 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, 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.
• The effects of combination tivozanib and nivolumab on the developing human fetus are unknown. For this reason and because tyrosine kinase inhibitors and immunotherapy agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. (refer to MDA Policy CLN 1114) This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following: * Postmenopausal (no menses in greater than or equal to 12 consecutive months). * History of hysterectomy or bilateral salpingo-oophorectomy. * Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy). * History of bilateral tubal ligation or another surgical sterilization procedure. Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device, Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• 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 4 months after completion of combination tivozanib and nivolumab administration.
• Participants or their legally acceptable representative (LAR) must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal participant care.
Exclusion Criteria:
• Prior tivozanib therapy.
• Prior nivolumab therapy.
• 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.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to tivozanib or nivolumab.
• Uncontrolled hypertension defined as systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 100 mmHg on 2 or more antihypertensive medications, documented on 2 consecutive measurements taken at least 2 hours apart. Anti-hypertensives must not have been increased 30 days prior to enrollment.
• History of autoimmune disorders except for the following:
• Patients with vitiligo or alopecia
• Hypothyroidism (e.g. following Hashimoto syndrome) that is stable on thyroid hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active autoimmune disease requiring treatment in the last 3 years may be included after consultation with study MDA lead Principal Investigator
• Active human immunodeficiency virus (HIV) infection unless patients are on effective anti-retroviral therapy with undetectable viral load within 6 months.
• Has evidence of any other medical conditions, psychiatric condition, physical examination or laboratory findings that may interfere with the planned treatment, affect subject compliance or place the subject at high risk from treatment-related complications in the opinion of the local principal investigator (PI).
• Current systemic corticosteroid use greater than prednisone 10 mg daily or equivalent.
• Pregnant women are excluded from this study because tivozanib and nivolumab are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with tivozanib and nivolumab, breastfeeding should be discontinued if the mother is treated with tivozanib and nivolumab.
• Receiving concomitant CYP3A inducers.
DRUG: Tivozanib, DRUG: Nivolumab
Renal Cell Carcinoma, Kidney
UT Southwestern
The PEERLESS II Study
This study is a prospective, multicenter, randomized controlled trial of the FlowTriever System plus anticoagulation compared to anticoagulation alone for intermediate-risk acute PE.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Camille.Harry@UTSouthwestern.edu
Rehan Quadri
ALL
18 Years and over
NA
NCT06055920
STU-2023-1010
Inclusion Criteria:
• Age at enrollment ≥ 18 years
• Objective evidence of a proximal filling defect in at least one main or lobar pulmonary artery, as confirmed by CTPA, pulmonary angiography, or other imaging modality
• RV dysfunction, as defined as one or more of the following: RV/LV ratio ≥ 0.9 or RV dilation or hypokinesis
• At least two additional risk factors, identified by at least one measure in two separate categories noted below: a. Hemodynamic: i. SBP 90-100mmHg ii. Resting heart rate \> 100 bpm b. Biomarker: i. Elevated\* cardiac troponin (troponin I or troponin T, conventional or high sensitivity) ii. Elevated\* BNP or NT-proBNP iii. Elevated venous lactate ≥2 mmol/L \* Elevated, meaning at or above the upper limit of normal, per local standards for the assay used c. Respiratory: i. O2 saturation \< 90% on room air ii. Supplemental O2 requirement ≥ 4 L/min iii. Respiratory rate ≥ 20 breaths/min iv. mMRC score \> 0
• Symptom onset within 14 days of confirmed PE diagnosis
• Willing and able to provide informed consent
Exclusion Criteria:
• Unable to be anticoagulated with heparin, enoxaparin or other parenteral antithrombin
• Presentation with hemodynamic instability\* that meets the high-risk PE definition in the 2019 ESC Guidelines1, including ANY of the following
• Cardiac arrest OR
• Systolic BP \< 90 mmHg or vasopressors required to achieve a BP ≥ 90 mmHg despite adequate filling status, AND end-organ hypoperfusion OR
• Systolic BP \< 90 mmHg or systolic BP drop ≥ 40 mmHg, lasting longer than 15 min and not caused by new-onset arrhythmia, hypovolemia, or sepsis \* Patients who are stable at time of screening or randomization (i.e., SBP ≥ 90 mmHg and adequate organ perfusion without catecholamine or vasopressor infusion) may be included despite initial presentation including temporary, low-dose catecholamines or vasopressors, or temporary fluid resuscitation.
• Known sensitivity to radiographic contrast agents that, in the Investigator's opinion, cannot be adequately pre-treated
• Imaging evidence or other evidence that suggests, in the opinion of the Investigator, the patient is not appropriate for catheter-based intervention (e.g., inability to navigate to target location, clot limited to segmental/subsegmental distribution, predominately chronic clot)
• End stage medical condition with life expectancy \< 3 months, as determined by the Investigator
• Current participation in another drug or device study that, in the investigator's opinion, would interfere with participation in this study
• Current or history of chronic thromboembolic pulmonary hypertension (CTEPH) or chronic thromboembolic disease (CTED) diagnosis, per 2019 ESC Guidelines1
• If objective testing was performed\*, estimated RV systolic pressure \> 70 mmHg on standard of care echocardiography \* If clinical suspicion of acute-on-chronic PE, chronic obstruction, or chronic thromboembolism, echocardiographic estimated RVSP must be confirmed ≤70 mmHg to meet eligibility. Pressure assessment not required if Investigator attests to absence of such clinical suspicion
• Administration of advanced therapies (thrombolytic bolus, thrombolytic drip/infusion, catheter-directed thrombolytic therapy, mechanical thrombectomy, or ECMO) for the index PE event within 30 days prior to enrollment
• Ventricular arrhythmias refractory to treatment at the time of enrollment
• Known to have heparin-induced thrombocytopenia (HIT)
• Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (e.g., compromise the well-being or that could prevent, limit, or confound the protocol-specified assessments). This includes a contraindication to use of FlowTriever System per local approved labeling
• Subject is currently pregnant
• Subject has previously completed or withdrawn from this study
DEVICE: FlowTriever System, DRUG: Anticoagulation Agents
Pulmonary Embolism
Parkland Health & Hospital System
KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors (FIT-001)
This first-in-human (FIH) dose-escalation and dose-validation/expansion study will assess KO-2806, a farnesyl transferase inhibitor (FTI), as a monotherapy and in combination, in adult patients with advanced solid tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years to old
PHASE1
NCT06026410
STU-2024-1021
Inclusion Criteria:
* At least 18 years of age.
* Histologically or cytologically confirmed advanced solid tumors
* Arm #1 (Monotherapy): HRAS-mutant and/or amplified tumors (any solid tumor type); HRAS overexpression (only for HNSCC tumors); KRAS and/or NRAS, and/or HRAS-mutant and/or amplified NSCLC or CRC; KRAS-mutant and/or amplified PDAC
* Arm #2 (Combination): Patients who have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic RCC with predominantly clear cell subtype; non-clear cell RCC patients who are either treatment-naïve or have received any prior systemic treatment for locally advanced and metastatic RCC.
* Arm #3 (Combination): Patients with KRAS G12C-mutant locally advanced or metastatic NSCLC, CRC, or PDAC who have received at least 1 prior systemic therapy including available approved standard of care treatments.
* Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
* Karnofsky Performance Status of 70 or higher with no clinically significant deterioration over the previous 2 weeks.
* Acceptable liver, renal, endocrine, and hematologic function.
* Other protocol-defined inclusion criteria may apply.
Exclusion Criteria:
* Ongoing treatment with certain anticancer agents.
* Prior treatment with an FTI or HRAS inhibitor.
* Major surgery, other than local procedures, within 28 days prior to Cycle 1 Day 1, without complete recovery.
* Spinal cord compression, leptomeningeal disease, or clinically active CNS metastases.
* Toxicity (excluding alopecia) from prior therapy that has not been completely resolved to baseline at the time of consent.
* Active or prior documented autoimmune or inflammatory disorders within the past 5 years prior to Cycle 1 Day 1 (with exceptions).
* Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy.
* Inability to swallow, impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the trial drugs.
* Inadequate cardiac and/or vascular function, including receipt of treatment for unstable angina, myocardial infarction, and/or cerebro-vascular attack within the prior 6 months, mean QTcF ≥470 ms, or Class II or greater congestive heart failure.
* Other invasive malignancy within 2 years.
* Other protocol-defined exclusion criteria may apply. DRUG: Darlifarnib, DRUG: Cabozantinib, DRUG: Adagrasib
Solid Tumors With HRAS Alterations, Non Small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Pancreatic Ductal Adenocarcinoma (PDAC), Clear Cell Renal Cell Carcinoma (ccRCC), Renal Cell Carcinoma (Kidney Cancer), Colon, Kidney, Lung/Thoracic, Pancreas
HRAS, KRAS, NRAS, Farnesyl transferase inhibitor (FTI), Tyrosine Kinase inhibitor (TKI), Phase 1, KRAS G12C inhibitor, NSCLC, ccRCC, RCC, PDAC, CRC
UT Southwestern
Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study
This phase II/III trial examines whether patients who have undergone surgical removal of bladder, kidney, ureter or urethra, but require an additional treatment called immunotherapy to help prevent their urinary tract (urothelial) cancer from coming back, can be identified by a blood test. Many types of tumors tend to lose cells or release different types of cellular products including their DNA which is referred to as circulating tumor DNA (ctDNA) into the bloodstream before changes can be seen on scans. Health care providers can measure the level of ctDNA in blood or other bodily fluids to determine which patients are at higher risk for disease progression or relapse. In this study, a blood test is used to measure ctDNA and see if there is still cancer somewhere in the body after surgery and if giving a treatment will help eliminate the cancer. Immunotherapy with monoclonal antibodies, such as nivolumab and relatlimab, can help the body's immune system to attack the cancer, and can interfere with the ability of tumor cells to grow and spread. This trial may help doctors determine if ctDNA measurement in blood can better identify patients that need additional treatment, if treatment with nivolumab prolongs patients' life and whether the additional immunotherapy treatment with relatlimab extends time without disease progression or prolongs life of urothelial cancer patients who have undergone surgical removal of their bladder, kidney, ureter or urethra.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years and over
PHASE2
NCT05987241
STU-2024-0089
Inclusion Criteria:
* PRE-REGISTRATION: Histologically confirmed muscle-invasive urothelial carcinoma of the urethra, bladder, ureter or renal pelvis
* PRE-REGISTRATION: Variant histology, including neuroendocrine differentiation, sarcomatoid, micropapillary, glandular, trophoblastic, Mullerian, is allowed if urothelial cancer is predominant histology (any amount of squamous differentiation is allowed provided the tumor is not a pure squamous cell cancer)
* PRE-REGISTRATION: Patient must have had radical surgery (i.e., cystectomy and lymph node dissection or nephroureterectomy or ureterectomy) ≥ 3 weeks, but ≤ 12 weeks prior to pre-registration. Patients who have had a partial cystectomy as definitive therapy are not eligible
* PRE-REGISTRATION: No gross cancer at the surgical margins. Microscopic invasive urothelial carcinoma at the surgical margins (i.e., "positive margins") are allowed. Carcinoma in situ (CIS) at margins is considered negative margins
* PRE-REGISTRATION: No evidence of residual cancer or metastasis after radical cystectomy or nephroureterectomy or ureterectomy (imaging is not required prior to pre-registration but is required prior to registration)
* PRE-REGISTRATION: Have undergone a radical cystectomy nephroureterectomy, or ureterectomy with pathological evidence of urothelial carcinoma at high risk of recurrence as described in one of the two scenarios below (i or ii). The 7th edition of American Joint Committee on Cancer (AJCC) staging will be utilized.:
* (i) Patients who have not received neoadjuvant systemic therapy: pT3-pT4\* or pT0/x-pT4/N+ on radical surgery (i.e., cystectomy, nephroureterectomy, or ureterectomy) and are not eligible for adjuvant cisplatin chemotherapy
* (i) Patients ineligible for cisplatin due to at least one of the following criteria and reason for ineligibility should be documented:
* (i) Creatinine Clearance (using Cockcroft-Gault): \< 60 mL/min
* (i) Common Terminology Criteria for Adverse Events (CTCAE) version 5, grade \>= 2 audiometric hearing loss
* (i) CTCAE version 5, grade \>= 2 or above peripheral neuropathy
* New York Heart Association Class III heart failure
* (i) Eastern Cooperative Oncology Group (ECOG) performance status = 2
* (i) Patients who are eligible for cisplatin may be candidates if they refuse adjuvant cisplatin-based chemotherapy, despite being informed by the investigator about the treatment options. The patient's refusal must be documented.
* (i) Patients with pT2N0 urothelial cancer on radical surgery specimen (without prior neoadjuvant systemic therapy) with ctDNA(+) Signatera results based on an assay performed post-radical surgery as part of routine care outside of the study may proceed with pre-registration but require confirmation of ctDNA(+) Signatera testing on repeat "central testing" in the context of A032103 testing. Patients with pT2N0 with central testing not confirming ctDNA(+) will not be eligible for A032103 (Note: this is distinct from patients with ypT2N0 who are eligible based on ii).
* (ii) Patients who received neoadjuvant systemic therapy: ypT2-T4a and/or ypN+ on radical surgery (i.e., cystectomy. , nephroureterectomy, or ureterectomy) pathology specimen. Neoadjuvant systemic therapy may have included cisplatin-based chemotherapy, cisplatin-based chemotherapy plus PD-1/PD-L1 blockade, or enfortumab vedotin plus PD-1/PD-L1 blockade
* PRE-REGISTRATION: Available tumor tissue for central Signatera testing to be submitted at pre-registration. Central testing is defined as testing performed as part of the A032103 study prior to registration and is provided by the study and not routine standard commercial testing. Patients who have already had local Signatera testing performed as part of routine care will require repeat central testing as part of the A032103 study to be eligible for registration/randomization. Tumor tissue from the radical surgery specimen is preferred over tissue from prior diagnostic biopsy specimen (e.g., transurethral resection of bladder tumor specimen)
* PRE-REGISTRATION: Age \>= 18 years
* PRE-REGISTRATION: ECOG Performance Status 0-2
* PRE-REGISTRATION: Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects
* PRE-REGISTRATION: No postoperative/adjuvant systemic therapy after radical surgery
* PRE-REGISTRATION: No adjuvant radiation after radical surgery
* PRE-REGISTRATION: No treatment with any other type of investigational agent =\< 4 weeks before pre-registration
* PRE-REGISTRATION: Not have ever received prior treatment with LAG-3 blockade
* PRE-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
* PRE-REGISTRATION: Absolute Neutrophil Count (ANC) \>= 1,200/mm\^3
* PRE-REGISTRATION: Platelet count \>= 100,000/mm\^3
* PRE-REGISTRATION: Hemoglobin \>= 8 g/dL
* PRE-REGISTRATION: Creatinine =\< 1.5 x upper limit of normal (ULN) or calculated (calc.) creatinine clearance \> 30 mL/min (using either Cockcroft-Gault formula or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
* PRE-REGISTRATION: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3 x ULN
* PRE-REGISTRATION: Total bilirubin =\< 1.5 x upper limit of normal (ULN) (except in patients with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)
* PRE-REGISTRATION: For women of childbearing potential only: A negative urine or serum pregnancy test done =\< 14 days prior to pre-registration is required
* PRE-REGISTRATION: Not currently requiring hemodialysis
* PRE-REGISTRATION: No current or prior history of myocarditis
* PRE-REGISTRATION: No grade ≥ 3 immune related adverse event with prior PD-1/PD-L1 blockade
* PRE-REGISTRATION: No active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens- Johnson syndrome, or phospholipid syndrome because of the risk of recurrence or exacerbation of disease.
* PRE-REGISTRATION: Patients with vitiligo, endocrine deficiencies including type I diabetes mellitus, thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible.
* PRE-REGISTRATION: Patients with rheumatoid arthritis and other arthropathies, Sjögren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.
* PRE-REGISTRATION: No current pneumonitis or prior history of non-infectious pneumonitis that required steroids within the previous 5 years.
* PRE-REGISTRATION: No known active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected).
* PRE-REGISTRATION: 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.
* PRE-REGISTRATION: Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible.
* PRE-REGISTRATION: No concurrent antineoplastic therapy.
* PRE-REGISTRATION: No current immunosuppressive agents (with the exception of corticosteroids as described below).
* PRE-REGISTRATION: No condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of pre-registration (with the exception of steroid pre-medications for contrast allergies). Inhaled or topical steroids and adrenal replacement doses \< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
* REGISTRATION: Patient must have had radical cystectomy and lymph node dissection or nephroureterectomy or ureterectomy =\< 18 weeks prior to registration.
* REGISTRATION: Must have evaluable ctDNA Signatera assay result (i.e., ctDNA\[+\]or ctDNA\[-\]) based on test performed as part of central testing at pre-registration to A032103. Central testing is defined as testing performed as part of the A032103. Local/commercial testing results may not be used for registration to A032103
* Cisplatin-ineligible (or cisplatin-declining) patients with a pT2N0 urothelial cancer on cystectomy or nephroureterectomy or ureterectomy who were pre-registered based on routine standard care ctDNA(+) Signatera testing must have confirmed ctDNA(+) Signatera testing on central testing. If central Signatera testing yields a ctDNA(-) result, these patients are ineligible. NOTE: This is a distinct consideration from patients with ypT2-4 and/or ypN+ urothelial cancer (i.e., patients who had received neoadjuvant cisplatin-based chemotherapy) who are eligible with either ctDNA(+) or ctDNA(-) central Signatera testing
* REGISTRATION: All patients must have confirmed disease-free status defined as no measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, or definitive non-measurable radiographic metastatic disease, within 60 days prior to registration. Patients with equivocal nodes less than 15 mm in short axis, or \< 10 mm in long axis for non-lymph node lesions, not considered by the investigator to represent malignant disease will be eligible. Attempts should be made to resolve the etiology of equivocal lesions with complementary imaging (e.g., PET scan) or biopsy.
* REGISTRATION: No major surgery =\< 3 weeks before registration.
* REGISTRATION: 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 \[registered trademark\]) are live attenuated vaccines and are not allowed. Coronavirus disease 2019 (COVID-19) vaccines are not live vaccines and are allowed
* REGISTRATION: No change since registration in clinical condition and/or laboratory tests that would impact the safety of nivolumab +/- relatlimab administration in the opinion of the treating investigator
* COHORT B, ARM 4 PATIENTS INITIATING NIVOLUMAB AFTER CONVERSION OF ctDNA ASSAY FROM ctDNA(-) to ctDNA (+):
* Patient must have converted to ctDNA(+) during serial monitoring performed centrally in the setting of the A032103 study
* COHORT B, ARM 4 PATIENTS INITIATING NIVOLUMAB AFTER CONVERSION OF ctDNA ASSAY FROM ctDNA(-) to ctDNA (+):
* No evidence of metastatic disease on the most recent scheduled imaging assessment as outlined in the study calendar (no repeat imaging is necessary specifically at the time of the conversion from ctDNA\[-\] to ctDNA\[+\]).
* COHORT B, ARM 4 PATIENTS INITIATING NIVOLUMAB AFTER CONVERSION OF ctDNA ASSAY FROM ctDNA(-) to ctDNA (+):
* No change in clinical condition and/or laboratory tests that would impact the safety of nivolumab administration in the opinion of the treating investigator
* COHORT B, ARM 4 PATIENTS INITIATING NIVOLUMAB AFTER CONVERSION OF ctDNA ASSAY FROM ctDNA(-) to ctDNA (+):
* =\< 6 weeks from reporting of ctDNA(+) result to site (not from the date sample was drawn). PROCEDURE: Biospecimen Collection, OTHER: cfDNA or ctDNA Measurement, PROCEDURE: Computed Tomography, PROCEDURE: Cystoscopy, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Nivolumab, OTHER: Questionnaire Administration, BIOLOGICAL: Relatlimab
Muscle Invasive Bladder Urothelial Carcinoma, Muscle Invasive Renal Pelvis Urothelial Carcinoma, Muscle Invasive Ureter Urothelial Carcinoma, Muscle Invasive Urethral Urothelial Carcinoma, Stage II Bladder Urothelial Carcinoma AJCC v6 and v7, Stage III Bladder Urothelial Carcinoma AJCC v6 and v7, Stage IV Bladder Urothelial Carcinoma AJCC v7, Urinary Bladder
UT Southwestern
PSMA PET Response Guided SabR in High Risk Pca
Sequential cohort evaluation of ideal timing of imaging and treatment spacing to discern maximal PSMA (Prostate specific membrane antigen) PET (Positron Emission Tomography) response (PSMA-11 68Ga, Illucix) for adaptation of dominant intra-prostatic lesion tumor boost dose
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Neil Desai
MALE
18 Years to 99 Years old
PHASE1
NCT06044857
STU-2023-0566
Inclusion Criteria:
-Pathologically confirmed adenocarcinoma of the prostate (within 180 days of registration) of high risk by national comprehensive cancer network (NCCN) criteria as determined by \>=cT3a stage (AJCC 8th edition) OR PSA\>20ng/mL OR ISUP Grade Group 4-5 (Gleason Grade 8-10).
Age ≥ 18 years.
* Planned for definitive intent stereotactic ablative radiotherapy (SabR) with integrated dose boost to intra-prostatic tumor and androgen deprivation therapy (ADT) with baseline AUA IPSS \<=18 and prostate size \<=100cc
* Staging 68Ga PMSA-11 PET -CT or -MRI performed within 90 days of registration and before initiation of anti-androgen or androgen deprivation therapy and demonstrating no evidence of distant metastases by (PMSA avid or non-avid nodes \<=1.5cm short axis allowed). Conventional imaging (CT, bone scan, MRI) may also be used in addition to PMSA-PET, and definitive findings of distant extra-pelvic metastases on these scans are not allowed for enrollment.
* Staging 68Ga PSMA-11 PET -CT or -MRI demonstrating a PSMA-avid primary intra-prostatic target lesion amenable at investigator discretion to dose boost
* All men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of standard of care SabR and for a period of time of 6 months thereafter as per standard guidelines. Should a man's partner become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
* Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
* Prior curative intent local therapy (e.g. prostatectomy, radiotherapy, focal ablative therapy) for prostate cancer is not allowed, with following exceptions regarding androgen deprivation therapy (ADT)/anti-androgen therapy (AAT):
Prior androgen deprivation therapy (ADT) allowed if \<3 month total duration and stopped \>=3 months prior to registration with demonstration of non-castrate testosterone recovery (\>50ng/dL) and meeting all other inclusion criteria.
Ongoing androgen deprivation therapy (ADT) is allowed if \<=60 days total duration AND meeting following criteria:
If GnRH agonist used (e.g. leuprolide), bicalutamide must have been used for at least 30 days +/-14 days from start of GnRH agonist.
All other inclusion criteria.
* Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
* History of allergic reactions to PMSA-11 68Ga imaging agent.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
* Prior pelvic radiotherapy other than cutaneous/superficial treatments. DRUG: 68-Ga PSMA11
Prostate Adenocarcinoma, Prostate
UT Southwestern
IDE196 (Darovasertib) in Combination With Crizotinib as First-line Therapy in Metastatic Uveal Melanoma
This is a Phase 2/3, multi-arm, multi-stage, open-label study of human leukocyte antigen (HLA)-A\*02:01 negative participants with metastatic uveal melanoma (MUM) who will be randomized to receive either IDE196 + crizotinib or investigator's choice of treatment (pembrolizumab, ipilimumab + nivolumab, or dacarbazine).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Sanjay Chandrasekaran
ALL
18 Years and over
PHASE2
NCT05987332
STU-2023-1054
Inclusion Criteria:
* Histological or cytological confirmed Metastatic Uveal Melanoma
* HLA-A\*02:01 negative
* No prior systemic therapy in the metastatic or advanced setting or regional or liver-directed therapy. Ablations or surgical resection of oligometastatic disease, and neoadjuvant or adjuvant therapy is allowed
* Measurable disease per RECIST 1.1
* Able to be safely administered and absorb study therapy
* ECOG performance status 0 or 1
* Life expectancy of ≥3 months
* Adequate organ function
Exclusion Criteria:
* Previous treatment with a PKC inhibitor (including prior treatment with IDE196), an inhibitor directly targeting MET, or an inhibitor directly targeting GNAQ/11
* Concurrent malignant disease
* AEs from prior anti-cancer therapy that have not resolved to Grade ≤1
* Symptomatic or untreated central nervous system (CNS) metastases, or CNS metastases that require corticosteroids
* High risk of syncope
* Known AIDS related illness or active Hep B/C
* Active adrenal insufficiency, active colitis, or active inflammatory bowel disease
* History of interstitial lung disease, active pneumonitis, or history of pneumonitis
* Active infection requiring systemic antibiotic therapy
* Use of hematopoietic colony-stimulating factors (CSF) prior to start of study drug
* Females who are pregnant or breastfeeding
* History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs or monoclonal antibodies
* Contraindication for treatment with investigator's choice therapies as per applicable labelling
* History of stroke within the last 6 months of the first dose of study drug
* Has any other condition that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the opinion of the investigator, would make the participant inappropriate for entry into the study, including institutionalization on the basis of an official or court order DRUG: IDE196, DRUG: Crizotinib, DRUG: Pembrolizumab, DRUG: Ipilimumab, DRUG: Nivolumab, DRUG: Dacarbazine
Metastatic Uveal Melanoma, Melanoma, skin
IDE196, Darovasertib, Protein Kinase C, Metastatic Uveal Melanoma, Melanoma, Ocular Oncology, Ophthalmology, Crizotinib, Ocular melanoma
UT Southwestern
Study of Tinengotinib VS. Physician's Choice a Treatment of Subjects With FGFR-altered in Cholangiocarcinoma (FIRST-308)
This study is a Phase III, Randomized, Controlled, Global Multicenter Study to Evaluate the Efficacy and Safety of Oral Tinengotinib versus Physician's Choice in Subjects with Fibroblast Growth Factor Receptor (FGFR)-altered, Chemotherapy- and FGFR Inhibitor-Refractory/Relapsed Cholangiocarcinoma
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Hsieh
ALL
18 Years and over
PHASE3
NCT05948475
STU-2024-0123
Inclusion Criteria:
• ≥ 18 years of age at the time of signing the informed consent form (ICF).
• Histologically or cytologically confirmed CCA/adenocarcinoma of biliary origin with radiological evidence of unresectable or metastatic disease.
• Documentation of FGFR2 fusion/rearrangement gene status
• Subjects must have received at least one line of prior chemotherapy and exactly one FDA approved FGFR inhibitor.
Exclusion Criteria:
• Prior receipt of two or more FGFR inhibitors, either approved or investigational drugs.
• Subjects with known brain or central nervous system (CNS) metastases that have radiologically or clinically progressed in the 28 days prior to initiation of therapy. Subjects with asymptomatic brain/CNS metastases or treated brain/CNS metastases that have been clinically stable for 14 days on steroids without escalation of steroids are eligible for enrollment.
• Subjects with a known concurrent malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, including those that have previously undergone potentially curative therapy.
• Subjects who have received prior systemic therapy or investigational study drug ≤ 5 half-lives or 14 days, whichever is shorter, prior to starting the study drug or who have not recovered (grade ≤ 1 or at pretreatment baseline except tolerable grade 2 alopecia, fatigue/asthenia, and neuropathy due to trauma) from adverse events (AEs) of prior therapy.
• Concurrent anticancer therapy including chemo-, immune-, or radiotherapy. Hormone therapy may be allowed with Sponsor approval.
• Subjects who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting the study drug or who have not recovered from AEs of prior therapy.
• Subjects with uncontrolled hypertension (defined as blood pressure of ≥ 150 mm Hg systolic and/or ≥ 90 mm Hg diastolic despite adequate treatment with antihypertensive medications at screening)
DRUG: Tinengotinib 8 mg, DRUG: Tinengotinib 10 mg, DRUG: Physician's Choice
Cholangiocarcinoma, Other Digestive Organ
Refractory/Relapsed Cholangiocarcinoma
UT Southwestern; Parkland Health & Hospital System
Sequential Treatment of Cabozantinib for Advanced Renal Cell Carcinoma (RCC)
The goal of this clinical trial is to learn about the effects of a higher dose of ncabozantinib in patients with advanced renal cell carcinoma who have progressed on or after receiving cabozantinib treatment.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years and over
PHASE2
NCT05931393
STU-2023-0439
Inclusion Criteria:
• Patients with advanced RCC (defined as locally advanced unresectable or metastatic) of any histology who progressed on/after cabozantinib monotherapy in any line of treatment. Patient must have cabozantinib sensitive disease (prior treatment with cabozantinib ≥ 6 months)
• Ability to tolerate prior cabozantinib at 60mg PO daily with manageable toxicity profile at the respective doses, at investigator discretion
• Prior PD-1 inhibitor/PD-L1 inhibitor allowed
• Evidence of measurable disease per RECIST 1.1
• For up to 5 patients opting into on-treatment biopsy, one of the following must be met:
• Archival tissue confirmed to be available and obtained within 30 days of informed consent as well as willingness to undergo an on-treatment biopsy at 12 weeks (+/- 7 days). OR
• Willingness to undergo a baseline biopsy prior to Cycle 1 Day1, as well as an on-treatment biopsy at 12 weeks (+/- 7 days).
• Age ≥ 18 at time of consent
• ECOG performance status ≤ 2
• Capable of understanding and complying with the protocol requirements and must have signed the informed consent document
• No washout period is needed for cabozantinib, minimum of 4 weeks or 4 half-lives washout, whichever is shorter, for other standard or experimental anti-cancer therapies.
• Recovery to baseline or ≤ Grade 1 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy
• Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment:
• Absolute neutrophil count (ANC) ≥ 1500/µL without granulocyte colony-stimulating factor (G-CSF) support
• White blood cell (WBC) count ≥ 2500/µL
• Platelets ≥ 100,000/µL without transfusion
• Hemoglobin ≥ 9 g/dL (≥ 90 g/L) (transfusion acceptable per investigator discretion)
• Alanine transaminase (ALT), AST and alkaline phosphatase (ALP) ≤ 3 x ULN. ALP ≤ 5x ULN with documented bone metastases
• Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert's disease ≤ 3x ULN)
• Serum albumin ≥ 2.8 g/dl
• Prothrombin (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test \< 1.3x the laboratory ULN
• Serum creatinine ≤ 1.5x ULN or calculated creatinine clearance ≥ 40mL/min (≥ 0.675mL/sec) using the Cockcroft-Gault equation: * Males: (140 - age) x weight (kg)/(serum creatinine \[mg/dL\] × 72) * Females: \[(140 - age) x weight (kg)/(serum creatinine \[mg/dL\] × 72)\] × 0.85
• Urine protein/creatinine ratio (UPCR) ≤1 mg/mg (≤113.2 mg/mmol), or 24h urine protein ≤1 g
• Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of cabozantinib Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Female subjects are considered to be of childbearing potential unless one of the following criteria is met: * documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), or * documented postmenopausal status (defined as 12 months of amenorrhea in a woman \> 45 years-of-age in the absence of other biological or physiological causes.
• In addition, females \< 55 years-of-age must have a serum follicle stimulating hormone (FSH) level \> 40 mIU/mL to confirm menopause.
Exclusion Criteria:
• Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for 1) at least 2 weeks after radiotherapy or 2) at least 4 weeks after major surgery (e.g., removal or biopsy of brain metastasis) prior to first dose of study treatment. Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment for the brain metastasis at the time of first dose of study treatment
• 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 are the following: 1) prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH). 2) 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
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders: 1) congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias; 2) uncontrolled hypertension defined as sustained blood pressure (BP) \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment within 1 week of treatment; 3) stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis \[DVT\], pulmonary embolism \[PE\]) within 6 months before first dose of study treatment. Note: subjects with a diagnosis of incidental, subsegmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation (see exclusion criterion #3.2.4) for at least 1 week before first dose of study treatment
• Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation, including 1) the subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction; 2) abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment
• Clinically significant hematuria, hematemesis, hemoptysis, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 6 weeks before first dose of study treatment. (Clinically significant hematuria defined by needing transfusion; clinically significant hematemesis or hemoptysis defined by needing hospital admission)
• Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation. Cavitary pulmonary lesions are allowed if not symptomatic.
• Lesions invading or encasing any major blood vessels
• Other clinically significant disorders that would preclude safe study participation
• Serious non-healing wound/ulcer/bone fracture
• Moderate to severe hepatic impairment (Child-Pugh B or C).
• Acute COVID-19 infection - clinical recovery from COVID-19 infection at least 14 days prior to enrollment allowed.
• Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 2 weeks before first dose of study treatment. Minor surgeries within 10 days before first dose of study treatment. Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible
• Corrected QT interval calculated by the Fridericia formula (QTcF) \> 500 ms per electrocardiogram (ECG) within 14 days before first dose of study treatment. Furthermore, subjects with a history of additional risk factors for torsades de pointes (e.g., long QT syndrome) are also excluded. Note: If a single ECG shows a QTcF with an absolute value \> 500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility.
• Pregnant or lactating females
• Inability to swallow tablets
• Previously identified allergy or hypersensitivity to components of the study treatment formulations or history of severe infusion-related reactions to monoclonal antibodies. Subjects with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption are also excluded
• Another malignancy within 2 years prior to first dose of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, Gleason 6 prostate cancer, or carcinoma in situ of cervix or breast
DRUG: Cabozantinib 80 MG
RCC, Renal Cell Carcinoma, Kidney
UT Southwestern
Disitamab Vedotin With Pembrolizumab vs Chemotherapy in Previously Untreated Urothelial Cancer Expressing HER2
This study will enroll participants with urothelial cancer (UC). UC can include cancer of the bladder, kidney, or the tubes that carry pee through the body (ureter, urethra). This study will try to find out if the drugs disitamab vedotin with pembrolizumab works better than platinum-containing chemotherapy to treat patients with UC. This study will also test what side effects happen when participants take these drugs together. A side effect is anything a drug does to the body besides treating the disease. Participants in this study will have cancer that has spread through the body (metastatic) or spread near where it started (locally advanced). In this study, there are 2 different groups. Participants will be assigned to a group randomly. Participants in the disitamab vedotin arm will get the study drug disitamab vedotin once every two weeks and pembrolizumab once every 6 weeks. Participants in the standard of care arm will get gemcitabine once a week for 2 weeks with either cisplatin or carboplatin once every 3 weeks.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Waddah Arafat
ALL
18 Years to old
PHASE3
NCT05911295
STU-2023-0936
Inclusion Criteria:
* Histopathological confirmation of locally advanced unresectable or metastatic urothelial carcinoma (LA/mUC), including UC originating from the renal pelvis, ureters, bladder, or urethra.
* Measurable disease by investigator assessment per RECIST v1.1.
* Participant must not have received prior systemic therapy for LA/mUC. Exception will be made for neoadjuvant or adjuvant therapy, if disease recurrence/progression occurred more than 12 months after the last dose of therapy.
* Eligible to receive cisplatin- or carboplatin-containing chemotherapy.
* Able to provide archived formalin-fixed paraffin-embedded tumor tissue blocks from a muscle-invasive or metastatic UC lesion or biopsy of metastatic UC prior to treatment initiation. If archival tissue is not available a newly obtained baseline biopsy of an accessible tumor lesion is required within 28 days of cycle 1 day 1.
* HER2 expression of 1+ or greater on immunohistochemistry (IHC).
* Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1, or 2 within 7 days prior to randomization.
Exclusion Criteria:
* Known hypersensitivity to disitamab vedotin, cisplatin, carboplatin, gemcitabine, or pembrolizumab or any of their components.
* History of severe/life threatening immune-related adverse event (irAE) with PD-(L)1 inhibitors are excluded.
* Central nervous system (CNS) and/or leptomeningeal metastasis. Participants with treated CNS metastases are permitted if all of the following are met.
* CNS metastases have been clinically stable for at least 4 weeks and baseline scans show no evidence of new or worsening CNS metastasis.
* Participant is on a stable dose of ≤ 10 mg/day of prednisone or equivalent for at least 2 weeks.
* History of or active autoimmune disease that has required systemic treatment in the past 2 years.
* Prior treatment with an agent directed to another stimulatory or co-inhibitory T cell receptor (including but not limited to CD137 agonists, CAR-T cell therapy, CTLA-4 inhibitors, or OX-40 agonists).
* Prior solid organ or bone marrow transplantation.
* Pleural effusion or ascites with symptoms or requiring symptomatic treatment.
* Estimated life expectancy \<12 week
* Prior treatment with an MMAE agent or anti-HER2 therapy DRUG: disitamab vedotin, DRUG: pembrolizumab, DRUG: gemcitabine, DRUG: cisplatin, DRUG: carboplatin
Urothelial Carcinoma, Urinary Bladder
Urothelial Cancer, LA/mUC, Bladder Cancer, HER2 Overexpression, HER2 Amplification, HER2, Seattle Genetics
UT Southwestern
Sonocloud-9 in Association With Carboplatin Versus Standard-of-Care Chemotherapies (CCNU or TMZ) in Recurrent GBM (SONOBIRD)
The brain is protected from any toxic or inflammatory molecule by the blood-brain barrier (BBB). This physical barrier is located at the level of the blood vessel walls. Because of these barrier properties, the blood vessels are also impermeable to the passage of therapeutic molecules from the blood to the brain. The development of effective treatments against glioblastoma is thus limited due to the BBB that prevents most drugs injected in the bloodstream from getting into brain tissue where the tumour is seated. The SonoCloud-9 (SC9) is an investigational device using ultrasound technology and specially developed to open the BBB in the area of and surrounding the tumour. The transient opening of the BBB allows more drugs to reach the brain tumour tissue. Carboplatin is a chemotherapy that is approved to treat different cancer types alone or in combination with other drugs, and has been used in the treatment of glioblastoma. Despite its proven efficacy in the laboratory on glioblastoma cells, carboplatin does not readily cross the BBB in humans. A clinical trial has shown that in combination with the SonoCloud-9, more carboplatin can reach the brain tumour tissue. The objective of the proposed trial is to show that the association - carboplatin with the SonoCloud-9 - will increase efficacy of the drug in patients with recurrent glioblastoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Toral Patel
ALL
18 Years to old
PHASE3
NCT05902169
STU-2023-1253
Inclusion Criteria:
• Histologically proven glioblastoma (WHO criteria 2021), absence of IDH mutation demonstrated by negative IDH1 R132H staining on Immunohistochemistry.
• Patient must have received prior first line therapy that must have contained both:
• Prior surgery or biopsy and standard fractionated radiotherapy (1.8-2 Gy/fraction, \>56 Gy\<66 Gy) or hypofractionated radiotherapy (15 x 2.66 Gy or similar regimen)
• One line of maintenance chemotherapy and/or immune- or biological therapy, (with or without Tumor-Treating Fields)
• First, unequivocal disease progression with
• measurable tumor (\>100 mm2 or 1 cm3, based on RANO criteria) documented (e.g., increase of 25% in tumor diameter) on MRI performed within 14 days of inclusion and,
• interval of a minimum of 12 weeks since the completion of prior radiotherapy, unless there is a new lesion outside the radiation field or unequivocal evidence of viable tumor on histopathological sampling
• Patient is candidate for craniotomy and at least 50% resection of enhancing region
• Maximal enhancing tumor diameter prior to inclusion ≤ 5 cm on T1w. (In case of planned lobectomy, post operative peritumoral brain or residual size ≤5 cm)
• WHO performance status ≤ 2 (equivalent to Karnofsky Performance Status (KPS) ≥ 70)
• Age ≥ 18 years
• Participant must be recovered from acute toxic effects (\
• ≥ 6 weeks of prior bevacizumab
• Adequate hematologic, hepatic, and renal laboratory values within 14 days of inclusion i.e.:
• Hemoglobin ≥ 10 g/dL, platelets ≥ 100,000/mm3, neutrophils ≥ 1500/mm3.
• Liver function test with ≤ grade 1 alterations, except if due to antiepileptic drug therapy or isolated increased bilirubin due to Gilbert syndrome
• Estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 m2 using Cockcroft Gault formula
• Patient able to understand clinical trial information and willing to provide signed and informed consent
• Patient of childbearing potential must have a negative pregnancy test within 14 days of inclusion and must agree to use a medically-acceptable method of birth control during the treatment period and, if randomized in the experimental arm, for at least 1 month after the last cycle of carboplatin
• A male patient must agree to use condoms during the treatment period and, if randomized in the experimental arm, for at least 3 months after the last cycle of carboplatin; the patient must also refrain from donating sperm during this period.
• Patient must be a beneficiary of a health plan that covers routine patient care costs. Patient must be a beneficiary of or affiliated with a social security scheme (according to country-specific requirements) Non-
Inclusion Criteria:
• Multifocal enhancing tumor on T1w (unless all localized in a 5 cm diameter area)
• Posterior fossa tumor
• Known BRAF/ NTKR mutated patients
• Patient at risk of surgery site infection (e.g., 2 or more previous craniotomies/neurosurgery within the last 3 months, poor skin condition, and/or previously infected surgical field, or any other condition that is of increased infectious risk in the opinion of the neurosurgeon)
• Patient treated at high, stable -or average- dose of corticosteroids (≥ 6 mg/day dexamethasone or equivalent) in the 7 days prior to inclusion. Patients on dexamethasone for reasons other than mass effect may still be enrolled.
• Contra-indication to carboplatin, CCNU or TMZ
• Known history of hypersensitivity reactions to perflutren lipid microsphere components or to any of the inactive ingredients in ultrasound resonator
• Patient has received bevacizumab for other reasons (such as tumor progression) than treating edema
• Peripheral neuropathy or neuropathy ≥ grade 2
• Uncontrolled epilepsy or evidence of intracranial pressure
• Patient with known intracranial aneurism or having presented intra-tumor significant spontaneous hemorrhage
• Patient with unremovable coils, clips, shunts, intravascular stents, and/or wafer, or reservoirs
• Patient with medical need to be on continued anti-platelet aggregation therapy and/or anticoagulation. Patients for whom anticoagulation/platelet aggregation can be temporarily interrupted may be eligible after discussion and prior authorization by the sponsor.
• Patient receiving enzyme-inducing antiepileptic drugs (namely phenytoin, carbamazepine and derivatives, phenobarbital), unless switched on another antiepileptic regimen
• History of other malignancy within 3 years prior to study start with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma, non-melanomatous skin cancer or carcinoma in situ of the uterine cervix
• Patient with known or suspected active or chronic infections
• Patient with known significant cardiac disease, known to have right-to-left shunts, severe pulmonary hypertension (pulmonary artery pressure \> 90 mm Hg), uncontrolled systemic hypertension, or acute respiratory distress syndrome
• Known sensitivity/allergy to gadolinium, or other intravascular contrast agents
• Patient with impaired thermo-regulation or temperature sensation
• Pregnant, or breastfeeding patient
• Any other serious patient medical or psychological condition that may interfere with adequate and safe delivery of treatment and care (e.g., positive human immunodeficiency virus \[HIV\] status, potential blood-borne infections,…), circumstance (e.g., sinus opening during surgery), psychological, morphological characteristics (e.g., skin characteristics, bone thickness), or any pre-existing comorbidities that in the investigator's opinion may prevent the implantation of the device, may impair the ability of the patient to receive treatment with SonoCloud-9 or may be confounding for evaluation of the clinical trial endpoints
• Patients under guardianship, curatorship, under legal protection or deprived of liberty by an administrative or judicial decision Exclusion Criterion: Occurrence of any major medical illnesses or impairments that in the Investigator's opinion may hampered the ability of the patient to receive treatment with SonoCloud-9 or may be confounding for evaluation of the clinical endpoints.
DEVICE: SonoCloud-9 (SC9), DRUG: Carboplatin, DRUG: Lomustine, DRUG: Temozolomide
Glioblastoma, Recurrent Glioblastoma, GBM, Brain and Nervous System
carboplatin, SonoCloud, blood-brain barrier, Low Intensity Pulsed Ultrasound (LIPU)
UT Southwestern
Clinical Study of Ivonescimab for First-line Treatment of Metastatic NSCLC Patients
This is a Phase 3 Randomized, double-blind, Multiregional Study of Ivonescimab Combined with Chemotherapy Versus Pembrolizumab Combined with Chemotherapy for the First-line Treatment of Metastatic Non-small Cell Lung Cancer. The primary endpoint is overall survival and progression free survival assessed by investigator. The key secondary endpoints include response and safety.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Mitchell von Itzstein
ALL
18 Years to old
PHASE3
NCT05899608
STU20251014
Inclusion Criteria:
* Age ≥ 18 years old at the time of enrollment
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
* Expected life expectancy ≥ 3 months
* Metastatic (Stage IV) NSCLC
* Histologically or cytologically confirmed squamous or non-squamous NSCLC
* Recorded measurement of the Tumor Proportion Score (TPS) for PD-L1 expression, irrespective of the PD-L1 expression, prior to randomization
* At least one measurable noncerebral lesion according to RECIST 1.1
* No prior systemic treatment for metastatic NSCLC
Exclusion Criteria:
* Histologic or cytopathologic evidence of the presence of small cell lung carcinoma
* Known actionable genomic alterations (EGFR, ALK, ROS1, and BRAF V600E) or genes for which first-line approved therapies are available.
* For non-squamous histology patients, actionable driver mutation testing results are required before randomization.
* Has received any prior therapy for NSCLC in the metastatic setting
* Tumor invasion, encasement of organs (e.g. heart, trachea, esophagus, central bronchi), or major blood vessels (e.g aorta, central veins), if poses a significant increased risk of bleeding. BIOLOGICAL: Ivonescimab Injection, BIOLOGICAL: Pembrolizumab Injection
Non-Small Cell Lung Cancer, Lung/Thoracic
UT Southwestern
A Safety and Efficacy Study of HCB101, Fc-fusion Protein Targeting SIRPα-CD47 Pathway, in Solid or Hematological Tumors
The purpose of this study is to find out whether IV injection of HCB101 is an effective treatment for different types of advanced solid tumors or relapsed and refractory non-Hodgkin lymphoma and what side effects (unwanted effects) may occur in subjects aged 18 years old and above.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years and over
PHASE1
NCT05892718
STU-2023-1031
Inclusion Criteria:
• Able to understand and willing to sign the ICF.
• Male and female subjects of ≥18 years of age.
• Histologically/cytologically confirmed, locally advanced solid tumor: subjects with histologically or cytologically confirmed advanced solid tumors refractory to standard therapy, or for which no standard treatment exists or non-Hodgkin lymphoma, relapsed or refractory to at least 2 prior lines of therapy.
• For subjects with advanced solid tumor - must have at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at baseline.
• For subjects with non-Hodgkin lymphoma - must have non-Hodgkin lymphoma that is measurable or assessable for response per Lugano Classification (with 2016 refinement).
• Must have ECOG performance status of 0 to 2 at Screening.
• Able to provide tumor tissue samples.
• Have life expectancy of ≥12 weeks.
Exclusion Criteria:
• With known history of hypersensitivity to any components of HCB101.
• Known active or untreated CNS metastases and/or carcinomatous meningitis.
• Have undergone a major surgery or radical radiotherapy or palliative radiotherapy or have used a radioactive drug that is not completed at least 2 weeks prior to the first dose of HCB101.
• Clinically significant cardiovascular condition.
• Any previous treatment-related toxicities which have not recovered to ≤ Grade 1 as evaluated by National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 or baseline, except alopecia and anemia.
• With known inherited or acquired bleeding disorder or bleeding diathesis. .
• Have RBC transfusion within 4 weeks prior to Screening.
• With a previously documented diagnosis of hemolytic anemia or Evans Syndrome in the last 3 months.
• Any investigational or approved systemic cancer therapy.
• Active use of vitamin K antagonist anticoagulant like warfarin. Use of low molecular weight heparin and factor Xa inhibitors will be permitted on case by case basis. There will be no restriction for daily aspirin ≤ 81 mg/QD.
• Have used herbal medication within 14 days prior to the first dose of HCB101.
• Have received any treatment targeting the CD47 or SIRPα pathway.
• Have other malignancies requiring treatment within 2 years prior to the first dose of HCB101.
• Participation in another clinical study with an investigational product administered in the last 14 days prior to receiving the first dose of HCB101.
• An investigational device used within 28 days prior to the first dose of HCB101.
• Positive for hepatitis B, active hepatitis C infections, positive for HIV, or known active or latent tuberculosis.
• Known to have a history of alcoholism or drug abuse.
DRUG: HCB101
Advanced Solid Tumor, Refractory Non-Hodgkin Lymphoma, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Hodgkins Lymphoma, Kaposis sarcoma, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Multiple Myeloma, Non-Hodgkins Lymphoma, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Stomach, Thyroid, Urinary Bladder
Immunotherapy, CD47, SIRPα, Solid Tumor, Lymphoma
UT Southwestern; Parkland Health & Hospital System
Testing Pump Chemotherapy in Addition to Standard of Care Chemotherapy Versus Standard of Care Chemotherapy Alone for Patients With Unresectable Colorectal Liver Metastases: The PUMP Trial
This phase III trial compares hepatic arterial infusion (HAI) (pump chemotherapy) in addition to standard of care chemotherapy versus standard of care chemotherapy alone in treating patients with colorectal cancer that has spread to the liver (liver metastases) and cannot be removed by surgery (unresectable). HAI uses a catheter to carry a tumor-killing chemotherapy drug called floxuridine directly into the liver. HAI is already approved by the Food and Drug Administration (FDA) for use in metastatic colorectal cancer to the liver, but it is only available at a small number of hospitals, and most of the time it is not used until standard chemotherapy stops working. Standard chemotherapy drugs 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 HAI to standard chemotherapy may be effective in shrinking or stabilizing unresectable colorectal liver metastases.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Cecilia Ethun
ALL
18 Years and over
PHASE3
NCT05863195
STU-2024-0075
Inclusion Criteria:
* Patient must be \>= 18 years of age
* Patient must have confirmed unresectable liver confined metastatic colorectal cancer (CRC).
* Patient must not have radiographically or clinically evident extrahepatic disease (including but not limited to radiographically positive periportal lymph nodes).
* NOTE: Patients found to have positive periportal nodes at the time of HAI placement can remain on study.
* Patient may have calcified pulmonary nodules, and/or =\< 5 indeterminate and stable (for a minimum of 3 months on chemotherapy) pulmonary nodules each measuring =\< 6 mm in maximal axial dimension.
* Patient's primary tumor may be in place.
* Patient must have received 3-6 months of previous first-line chemotherapy that meet one of the following three criteria: a) have received at least 6 but no more than 12 cycles of first-line cytotoxic chemotherapy (where 1 cycle = 14 days) OR b) have received at least 4 but no more than 8 cycles of first-line cytotoxic chemotherapy (where 1 cycle = 21 days) OR c) have developed new colorectal liver metastases (CRLM) within 12 months of completing adjuvant systemic therapy for stage II-III colorectal cancer.
* NOTE: First-line chemotherapy may have included any of the following regimens as listed in the National Comprehensive Cancer Network (NCCN) Guidelines: leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX) (or equivalent), leucovorin calcium (calcium folinate), 5-fluorouracil, and irinotecan (FOLFIRI) (or equivalent), leucovorin calcium (calcium folinate), 5-fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI), each with or without any of the following: bevacizumab, cetuximab, or panitumumab.
* Patient must have stable or responding disease on first-line chemotherapy by RECIST 1.1 criteria
* Patient must meet the following criteria for technical unresectability:
* A margin-negative resection requires resection of three hepatic veins, both portal veins, or the retrohepatic vena cava OR a resection that leaves less than two adequately perfused and drained segments.
* NOTE: Institutional multidisciplinary review is required to confirm unresectability and rule out radiographically positive extrahepatic disease.
* Patient must undergo CT angiography (chest/abdomen/pelvis) to confirm acceptable hepatic arterial anatomy for HAI and to rule out extrahepatic disease within 4 weeks prior to randomization.
* Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 and be clinically fit to undergo surgery as determined by the pre-operative evaluation.
* Leukocytes \>= 3,000/mcL (obtained =\< 14 days prior to protocol randomization)
* Absolute neutrophil count (ANC) \>= 1,500/mcL (obtained =\< 14 days prior to protocol randomization)
* Platelets \>= 100,000/mcL (obtained =\< 14 days prior to protocol randomization)
* Total Bilirubin =\< 1.5 mg/dL (obtained =\< 14 days prior to protocol randomization)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) =\< 3.0 x institutional upper limit of normal (ULN) (obtained =\< 14 days prior to protocol randomization)
* Creatinine =\< 1.5 x institutional ULN OR creatinine clearance \>= 50 mL/min calculated by the Cockcroft-Gault method (obtained =\< 14 days prior to protocol randomization)
* Calcium \>= institutional lower limit of normal (LLN)
* 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.
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial. Testing for HIV is not required for entry onto the study
Exclusion Criteria:
* Patient must not have a liver tumor burden exceeding 70% of total liver volume.
* Patient must not have had prior radiation to the liver (prior radiation therapy to the pelvis is acceptable if completed at least 2 weeks prior to randomization).
* Patient must not have had prior trans-arterial bland embolization, chemoembolization (TACE) or radioembolization (TARE).
* Patient must not have had prior treatment with HAI/floxuridine (FUDR)
* Patient must not have microsatellite instability-high (MSI-H) colorectal cancer.
* Patient must not have CRLM that could be resected with 2-stage hepatectomy, including associating liver partition and portal vein ligation (ALPPS).
* Patient must not have an active infection, serious or non-healing active wound, ulcer, or bone fracture.
* Patient must not have any serious medical problems which would preclude receiving the protocol treatment or would interfere with the cooperation with the requirements of this trial.
* Patient must not have cirrhosis and/or clinical or radiographic evidence of portal hypertension
* 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 patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy.
* A patient of childbearing potential is defined as anyone, 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 must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study. BIOLOGICAL: Bevacizumab, BIOLOGICAL: Cetuximab, PROCEDURE: Computed Tomography, DRUG: Floxuridine, DRUG: Fluorouracil, PROCEDURE: Implantation, PROCEDURE: Intrahepatic Infusion Procedure, DRUG: Irinotecan, DRUG: Leucovorin, DRUG: Oxaliplatin, BIOLOGICAL: Panitumumab, PROCEDURE: Single Photon Emission Computed Tomography
Metastatic Colorectal Carcinoma, Metastatic Malignant Neoplasm in the Liver, Stage IV Colorectal Cancer AJCC v8, Unresectable Colorectal Carcinoma, Colon, Liver, Rectum
UT Southwestern; Parkland Health & Hospital System