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520 Study Matches
Five or Ten Year Colonoscopy for 1-2 Non-Advanced Adenomatous Polyps (FORTE)
This trial examines colorectal cancer incidence in participants with 1 to 2 non-advanced adenomas randomized to surveillance colonoscopy at 10 years compared to participants randomized to surveillance colonoscopy at 5 and 10 years.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Luke Engelking
35166
All
50 Years to 70 Years old
N/A
NCT05080673
STU-2023-0888
Inclusion Criteria:
• • The participant must have signed and dated an IRB-approved consent form that conforms to federal and institutional guidelines.
• Participants with a first-time diagnosis of 1-2 non-advanced tubular adenomas (less than 10 mm without tubulovillous or villous changes or high grade or severe dysplasia) from the qualifying colonoscopy within 4 years prior to randomization.
• Sessile serrated polyps/adenomas, as long as they do not meet the criteria for advanced adenomas, will be considered as non-advanced adenomas.
• Qualifying colonoscopy must be a complete colonoscopy with visualization of the cecum and with adequate cleansing within 4 years prior to randomization.
• Complete excision of all observed polyps in qualifying colonoscopy
• Participants must be able to read or understand English or Spanish.
Exclusion Criteria:
• • Prior history of colorectal cancer or colorectal adenomas including sessile serrated polyps/adenomas excluding those found on the qualifying colonoscopy.
• Prior history of a hyperplastic polyp measuring greater than or equal to 1 cm in size.
• Traditional serrated adenomas found on the qualifying colonoscopy.
• Hyperplastic polyp measuring less than or equal to 1 cm in size found on the qualifying colonoscopy.
• Previous malignancies unless the patient has been disease-free for 5 or more years prior to randomization and is deemed by the physician to be at low risk for recurrence. Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: all in situ cancers and basal cell and squamous cell carcinoma of the skin.
• Colonoscopy performed after the qualifying colonoscopy but prior to randomization.
• Incomplete qualifying colonoscopy (e.g., cecum not visualized).
• Incomplete endoscopic excision of adenomatous polyps based on colonoscopist impression at qualifying colonoscopy. (Excision of all hyperplastic rectosigmoid polyps is not required.)
• Sub-total colectomy or total proctocolectomy. (Segmental resections are allowed.)
• Family history of CRC diagnosed at greater than or equal to 60 years of age in a first degree relative (mother, father, child, sibling) or in two first degree relatives with CRC at any age.
• Participants with a clinical diagnosis of a significant heritable risk for colorectal cancer (Familial Adenomatous Polyposis, Hereditary Nonpolyposis Colorectal Cancer [Lynch Syndrome]).
• Participants tested positive for a Familial Adenomatous Polyposis, Hereditary Nonpolyposis Colorectal Cancer [Lynch Syndrome] genetic mutation that increases risk of colorectal cancer.
• Inflammatory bowel disease (e.g., Crohn's Disease, ulcerative colitis).
• Life expectancy less than 10 years due to comorbid conditions in the opinion of the investigator.
• Other comorbid conditions that would prevent the participant from having colonoscopies or would prevent required follow-up.
Procedure: 5-year and 10 Year Surveillance Colonoscopy after Qualifying Colonoscopy
Adenocarcinoma of the Rectum, Adenocarcinoma of the Colon, Colon, Rectum
UT Southwestern
A Study to Investigate Safety and Tolerability of TransCon IL-2 β/γ Alone or in Combination With Pembrolizumab and/or Chemotherapy or TransCon TLR7/8 Agonist in Adult Participants With Locally Advanced or Metastatic Solid Tumor Malignancies (IL Believe)
TransCon IL-2 β/γ is an investigational drug being developed for treatment of locally advanced or metastatic solid tumors. This is a first-in-human, open-label, Phase 1/2, dose escalation and dose expansion study of TransCon IL-2 β/γ as monotherapy or in combination therapy in adult participants with advanced or metastatic solid tumors. Given the unique PK profile enabled by the TransCon technology, TransCon IL-2 β/γ presents the opportunity to enhance the therapeutic index of current IL-2 therapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Miller
14954
All
18 Years and over
Phase 1/Phase 2
NCT05081609
STU-2023-0034
Key
• At least 18 years of age
• Demonstrated adequate organ function at screening
• Life expectancy >12 weeks as determined by the Investigator
• At least 1 lesion of measurable disease, except for Post Anti-PD-1 Melanoma and 2L+ Cervical Cancer (at least 2 lesions of measurable disease)
• Female and male participants of childbearing potential who are sexually active must agree to use highly effective methods of contraception
• Participants must have histologically confirmed locally advanced, recurrent, or metastatic solid tumor malignancies that cannot be treated with curative intent (surgery or radiotherapy), with the exception of the neoadjuvant cohorts
• Part 1 and Part 2: Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
• Part 3: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Part 1 and Part 2: Participants who have undergone treatment with anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody must have a washout of at least 4 weeks from the last dose and evidence of disease progression per investigator assessment before Cycle 1 Day 1 (C1D1)
• Part 1 and Part 2: Participants who have previously received an immunotherapy prior to C1D1 must have any immune-related toxicities resolved to ≤Grade 1 or baseline (prior to the immunotherapy) to be eligible, with the exception of participants on well controlled physiologic endocrine replacement
• Part 3: Part 3, neoadjuvant cohorts: participants must have completely resectable disease Key
• Symptomatic central nervous system metastases
• Active autoimmune diseases, regardless of need for immunosuppressive treatment, with the exception of participants well controlled on physiologic endocrine replacement
• Any uncontrolled bacterial, fungal, viral, or other infection
• Significant cardiac disease
• A marked clinically significant baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >480 ms) [CTCAE Grade 1]) using Fridericia's QT correction formula
• Positive for HIV or has known active hepatitis B or C infection
• Known hypersensitivity to any study treatment(s) used in the specific study part/cohort
• Participants who have been previously treated with IL-2 or IL-2 variants (all participants), or TLR agonist (Part 3 only for Post Anti-PD-1 Melanoma, 2L+ Cervical Cancer, and Neoadjuvant Melanoma)
• Systemic immunosuppressive treatment with the exception for patients on corticosteroid taper (for example, for chronic obstructive pulmonary disease exacerbation).
• Vaccination with live, attenuated vaccines within 4 weeks of C1D1
• Treatment with any other anti-cancer systemic treatment (approved or investigational) or radiation therapy within 4 weeks of C1D1
• Part 3: Other active malignancies within the last 2 years
• Women who are breastfeeding or have a positive serum pregnancy test during screening
Inclusion Criteria:
• At least 18 years of age
• Demonstrated adequate organ function at screening
• Life expectancy >12 weeks as determined by the Investigator
• At least 1 lesion of measurable disease, except for Post Anti-PD-1 Melanoma and 2L+ Cervical Cancer (at least 2 lesions of measurable disease)
• Female and male participants of childbearing potential who are sexually active must agree to use highly effective methods of contraception
• Participants must have histologically confirmed locally advanced, recurrent, or metastatic solid tumor malignancies that cannot be treated with curative intent (surgery or radiotherapy), with the exception of the neoadjuvant cohorts
• Part 1 and Part 2: Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
• Part 3: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Part 1 and Part 2: Participants who have undergone treatment with anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody must have a washout of at least 4 weeks from the last dose and evidence of disease progression per investigator assessment before Cycle 1 Day 1 (C1D1)
• Part 1 and Part 2: Participants who have previously received an immunotherapy prior to C1D1 must have any immune-related toxicities resolved to ≤Grade 1 or baseline (prior to the immunotherapy) to be eligible, with the exception of participants on well controlled physiologic endocrine replacement
• Part 3: Part 3, neoadjuvant cohorts: participants must have completely resectable disease Key
Exclusion Criteria:
• Symptomatic central nervous system metastases
• Active autoimmune diseases, regardless of need for immunosuppressive treatment, with the exception of participants well controlled on physiologic endocrine replacement
• Any uncontrolled bacterial, fungal, viral, or other infection
• Significant cardiac disease
• A marked clinically significant baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >480 ms) [CTCAE Grade 1]) using Fridericia's QT correction formula
• Positive for HIV or has known active hepatitis B or C infection
• Known hypersensitivity to any study treatment(s) used in the specific study part/cohort
• Participants who have been previously treated with IL-2 or IL-2 variants (all participants), or TLR agonist (Part 3 only for Post Anti-PD-1 Melanoma, 2L+ Cervical Cancer, and Neoadjuvant Melanoma)
• Systemic immunosuppressive treatment with the exception for patients on corticosteroid taper (for example, for chronic obstructive pulmonary disease exacerbation).
• Vaccination with live, attenuated vaccines within 4 weeks of C1D1
• Treatment with any other anti-cancer systemic treatment (approved or investigational) or radiation therapy within 4 weeks of C1D1
• Part 3: Other active malignancies within the last 2 years
• Women who are breastfeeding or have a positive serum pregnancy test during screening
Drug: TransCon IL-2 β/γ, Drug: Pembrolizumab, Drug: Chemotherapy drug, Drug: TransCon TLR7/8 Agonist, Procedure: Surgery
Advanced Solid Tumor, Cervix, Other Female Genital, Metastatic Solid Tumor, Locally Advanced Solid Tumor, Platinum-resistant Ovarian Cancer, Post Anti-PD-1 Melanoma, 2L+ Cervical Cancer, Neoadjuvant Melanoma, Neoadjuvant Non-Small Cell Lung Cancer
UT Southwestern; Parkland Health & Hospital System
Study of ONO-4685 in Patients With Relapsed or Refractory T Cell Lymphoma
This study will investigate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ONO-4685 in patients with relapsed or refractory T cell Lymphoma
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Praveen Ramakrishnan Geethakumari
171719
All
18 Years and over
Phase 1
NCT05079282
STU-2022-0424
Inclusion Criteria
• Patients aged ≥ 18 years at time of screening
• Written informed consent by the patient or the patients' legally authorized representative prior to screening
• Patients with histologically or cytologically confirmed diagnosis of one of the following subtypes of T-cell lymphoma:
• Peripheral T-cell lymphoma (PTCL): Angioimmunoblastic T-cell lymphoma (AITL), PTCL, not otherwise specified (PTCL-NOS), nodal PTCL with T-follicular helper (TFH) and follicular T-cell lymphoma (FTCL)
• Cutaneous T-cell lymphoma (CTCL) (stages II-B, III, and IV): Mycosis fungoides (MF) and Sezary syndrome (SS)
• Patients must have received at least 2 prior systemic therapies.
• Patients with PTCL must have at least 1 measurable lesion
• Patients with CTCL must have assessable disease by response criteria for CTCL (Olsen EA, 2011)
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) = 0-2
• Life expectancy of at least 3 months
• Adequate bone marrow, renal and hepatic functions
• Patients with central nervous system (CNS) involvement
• Patients with Adult T-cell leukemia/lymphoma (ATLL)
• Prior allogeneic stem cell transplant
• Prior treatment with ONO-4685, anti-PD-1, anti-PD-L1, anticytotoxic T lymphocyte associated protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
• Patients with malignancies (other than T-cell lymphoma) except for completely resected basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, or any other malignancies that has not relapsed for at least 2 years
• History of severe allergy or hypersensitivity to any monoclonal antibodies, other therapeutic proteins or corticosteroid (e.g., dexamethasone)
• History of infection with Mycobacterium tuberculosis within 2 years prior to the first dose of study treatment
• Patients with systemic and active infection including human immunodeficiency virus (HIV), hepatitis B or C virus infection
• Patients not recovered to Grade 1 or stabilized from the adverse effects (excluding alopecia) of any prior therapy for their malignancies
• Women who are pregnant or lactating
• Patients aged ≥ 18 years at time of screening
• Written informed consent by the patient or the patients' legally authorized representative prior to screening
• Patients with histologically or cytologically confirmed diagnosis of one of the following subtypes of T-cell lymphoma:
• Peripheral T-cell lymphoma (PTCL): Angioimmunoblastic T-cell lymphoma (AITL), PTCL, not otherwise specified (PTCL-NOS), nodal PTCL with T-follicular helper (TFH) and follicular T-cell lymphoma (FTCL)
• Cutaneous T-cell lymphoma (CTCL) (stages II-B, III, and IV): Mycosis fungoides (MF) and Sezary syndrome (SS)
• Patients must have received at least 2 prior systemic therapies.
• Patients with PTCL must have at least 1 measurable lesion
• Patients with CTCL must have assessable disease by response criteria for CTCL (Olsen EA, 2011)
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) = 0-2
• Life expectancy of at least 3 months
• Adequate bone marrow, renal and hepatic functions
Exclusion Criteria:
• Patients with central nervous system (CNS) involvement
• Patients with Adult T-cell leukemia/lymphoma (ATLL)
• Prior allogeneic stem cell transplant
• Prior treatment with ONO-4685, anti-PD-1, anti-PD-L1, anticytotoxic T lymphocyte associated protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
• Patients with malignancies (other than T-cell lymphoma) except for completely resected basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, or any other malignancies that has not relapsed for at least 2 years
• History of severe allergy or hypersensitivity to any monoclonal antibodies, other therapeutic proteins or corticosteroid (e.g., dexamethasone)
• History of infection with Mycobacterium tuberculosis within 2 years prior to the first dose of study treatment
• Patients with systemic and active infection including human immunodeficiency virus (HIV), hepatitis B or C virus infection
• Patients not recovered to Grade 1 or stabilized from the adverse effects (excluding alopecia) of any prior therapy for their malignancies
• Women who are pregnant or lactating
Drug: ONO-4685
Lymphoid Leukemia, Relapsed or Refractory T Cell Lymphoma
ONO-4685, PD-1, CD3, Bispecific antibody, PTCL, AITL, PTCL-NOS, nodal PTCL with TFH, FTCL, CTCL, MF, SS
UT Southwestern
Premedication for Less Invasive Surfactant Administration Study (PRELISA) (PRELISA)
The purpose of this study is to conduct a double blinded randomized control trial to determine the safety and efficacy of using IV fentanyl and atropine prior to Less Invasive Surfactant Administration (LISA) procedure in preterm infants with Respiratory Distress Syndrome compared to the local standard of care to perform this procedure without any premedication. Hypothesis: In infants greater than or equal to 29 weeks gestational age requiring the Less Invasive Surfactant Administration procedure, premedication with a combination of IV atropine and IV fentanyl will be associated with fewer combined bradycardia events, defined as heartrate less than 100 beats per minute for longer than 10 seconds, and hypoxemia events, defined as saturations less than or equal to 80% for longer than 30 seconds, during the procedure compared with placebo. Specific Aims: - To determine if infants receiving IV fentanyl and atropine prior to LISA will have a decrease in hypoxemia and bradycardia events during the procedure compared to infants receiving placebo - To determine if infants receiving premedication prior to Less Invasive Surfactant Administration will have higher procedure first attempt success rate compared with infants receiving placebo - To determine the effect of premedication on cerebral oxygenation compared to placebo during and for 12 hours after Less Invasive Surfactant Administration using cerebral Near Infrared Spectroscopy - To determine the effect of premedication prior to Less Invasive Surfactant Administration on the need for mechanical ventilation for 24 hours after the procedure
Call 214-648-5005
studyfinder@utsouthwestern.edu, Kathryn.Mazioniene@UTSouthwestern.edu
Venkatakrishna Kakkilaya
125855
All
0 Hours to 72 Hours old
Phase 4
NCT05065424
STU-2021-0380
Inclusion Criteria:
• Infants ≥29 weeks gestational age between 0-72 hours of life on CPAP for respiratory support who qualify for the LISA procedure as determined by the primary team using Parkland OPTISURF guidelines
Exclusion Criteria:
• Infants requiring intubation prior to surfactant therapy
• Infants with known severe congenital anomalies (including complex congenital heart disease, airway, and central nervous system anomalies)
• Infants born to mothers with known opioid addiction or in a methadone treatment program
Drug: IV Atropine and Fentanyl Premedication Arm, Drug: IV Normal Saline Placebo Arm
Respiratory Distress Syndrome, Newborn, Lung/Thoracic
Premedication for Less Invasive Surfactant Administration, Fentanyl and Atropine for Less Invasive Surfactant Administration, Cerebral Near Infrared Spectroscopy monitoring in neonates, Premedication for LISA, Fentanyl and Atropine for LISA, Cerebral NIRS monitoring in neonates
Parkland Health & Hospital System
Evaluating the Addition of the Immunotherapy Drug Atezolizumab to Standard Chemotherapy Treatment for Advanced or Metastatic Neuroendocrine Carcinomas That Originate Outside the Lung
This phase II/III trial compares the effect of immunotherapy with atezolizumab in combination with standard chemotherapy with a platinum drug (cisplatin or carboplatin) and etoposide versus standard therapy alone for the treatment of poorly differentiated extrapulmonary (originated outside the lung) neuroendocrine cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). The other aim of this trial is to compare using atezolizumab just at the beginning of treatment versus continuing it beyond the initial treatment. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cisplatin and carboplatin are in a class of medications known as platinum-containing compounds that work by killing, stopping or slowing the growth of cancer cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair, and it may kill cancer cells. Giving atezolizumab in combination with a platinum drug (cisplatin or carboplatin) and etoposide may work better in treating patients with poorly differentiated extrapulmonary neuroendocrine cancer compared to standard therapy with a platinum drug (cisplatin or carboplatin) and etoposide alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Namrata Peswani
193600
All
18 Years and over
Phase 2/Phase 3
NCT05058651
STU-2023-0750
Inclusion Criteria:
• Participants must have histologically-confirmed (local site pathological confirmation sufficient) extrapulmonary poorly differentiated, neuroendocrine carcinoma (NEC)
• Participants must have disease that is unresectable or metastatic and not eligible for definitive therapy as deemed per the treating investigator
• Participants must have radiologically evaluable disease, measurable or non-measurable, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. All measurable and non-measurable lesions must be assessed by CT scan with IV contrast of the chest/abdomen/and pelvis (or CT chest without contrast and MRI abdomen/pelvis with gadolinium contrast, if contraindication to CT iodinated contrast) within 28 days prior to registration. While may be used for routine clinical evaluation, PET scans and bone scans alone are not acceptable for disease assessment while participating in this study. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form
• Participants must have brain MRI (or CT head with contrast if there is contraindication to MRI brain) if clinically indicated within 28 days prior to registration. Note: Brain imaging is not required in participants without known and/or clinical concern for brain metastases. Participants with asymptomatic central nervous system (CNS) metastases are eligible if one or more of the following apply:
• Participants who have received treatment for brain metastases must have:
• No evidence of radiological progression (by MRI brain or CT head with contrast if there is contraindication to MRI brain) within 28 days prior to registration
• Discontinued all corticosteroids at least 14 days prior to registration
• Participants with treatment-naive brain lesions must have:
• No lesion measuring > 2.0 cm in size in any axis
• MRI brain or CT head with contrast (if there is contraindication to MRI brain) demonstrating no evidence for mass effect, edema, or other impending neurological compromise within 28 days prior to registration
• No evidence of radiological progression (by MRI brain or CT head with contrast if there is contraindication to MRI brain) within 28 days prior to registration
• No need for > 2 mg of dexamethasone (or equivalent of > 10 mg prednisone) per day at time of registration
• Participants must not have symptomatic central nervous system (CNS) metastases
• Participants must not have known or suspected leptomeningeal disease
• Participants with prior history of non-metastatic (localized/locally advanced disease) extrapulmonary poorly differentiated NEC may have had prior platinum-based therapy +/- radiation +/- surgery provided that all therapy was completed >= 6 months prior to registration
• Participants must discontinue denosumab prior to study registration and plan to replace with a bisphosphonate while on the study
• Participants must not have had prior treatment for advanced or metastatic NEC EXCEPT one cycle of platinum (carboplatin/cisplatin) + etoposide is allowed prior to registration. Other chemotherapy regimens are not allowed. For participants with prostate or urothelial NEC, prior chemotherapy for the non-NEC component (e.g. adenocarcinoma or urothelial) is allowed as long as such therapy was completed >= 24 weeks prior to registration and participants have recovered from all prior toxicities to =< grade 1.
• Participants must not have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, CD137 agonists, anti-CTLA-4 agent, or any other immune checkpoint inhibitors for any neuroendocrine neoplasm. Immune checkpoint inhibitors given for other cancer indications are allowed provided last therapy was given at least 12 months prior to study registration
• Participants must not have received treatment with systemic immunostimulatory agents including, but not limited to, interferon and interleukin2 [IL-2] within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to registration
• Participants must not have had history of known severe allergy, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies, including to Chinese hamster ovary cell products or to any component of the atezolizumab formulation, cisplatin, carboplatin, or etoposide
• Participants must not be on active systemic therapy for another cancer with the exception of hormonal therapy including androgen deprivation therapy (e.g., gonadotropin-releasing hormone [GnRH] agonists or antagonists), which can be continued while participants are receiving protocol therapy. Use of enzalutamide or apalutamide is permitted after completion of chemotherapy and must be held during chemotherapy for participants receiving prior to enrollment. Use of darolutamide is permitted during chemotherapy. Glucocorticoid-containing regimens, including abiraterone, are not permitted.
• Participants must be >= 18 years of age
• Participants must have a Zubrod performance status of =< 2 within 28 days prior to registration
• Participants must have a complete medical history and physical exam within 28 days prior to registration
• Absolute neutrophil count (ANC) >= 1.5 x 10^9 /L (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
• Hemoglobin >= 9.0 g/dl (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
• Platelet count >= 100 x 10^9/L (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
• Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x institutional upper limit of normal (ULN) (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
• Serum total bilirubin =< 1.5 x ULN (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
• Adequate renal function as defined by any 1 of the following: 1) Measured creatinine clearance (CL) > 50 mL/min OR 2) Calculated creatinine CL > 50 mL/min by the Cockcroft-Gault formula OR by 24-hour urine collection for determination of creatinine clearance (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
• Participants must not have uncontrolled or symptomatic hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > ULN) within 14 days prior to registration. Participants who have asymptomatic hypercalcemia are eligible provided that medical therapy to treat the hypercalcemia is planned
• Participants must not have a diagnosis of immunodeficiency nor be receiving systemic steroid therapy (equivalent of > 20 mg of hydrocortisone per day) or any other form of immunosuppressive therapy within 14 days prior to registration
• Participants must not have active or history of autoimmune disease or immune deficiency, including, but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study
• Patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Rash must cover < 10% of body surface area
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids
• No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
• Participants must not have history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. NOTE: History of radiation pneumonitis in the radiation field (fibrosis) is permitted
• Participants must not have significant cardiovascular disease, such as New York Heart Association class II or greater cardiac disease, myocardial infarction within 3 months prior to registration, unstable arrythmias, or unstable angina
• Participants must not have had a major surgical procedure other than for diagnosis within 28 days prior to registration. Participant must not plan to receive a major surgical procedure during the course of protocol treatment. NOTE: Patient port placement is not considered a major surgery
• Participants must not have severe infections (i.e., Common Terminology Criteria for Adverse Events [CTCAE] grade >= 2) at time of registration, including but not limited to hospitalization for complications for infection, bacteremia, or severe pneumonia
• Participants must not have known active tuberculosis
• Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load, with testing performed as clinically indicated
• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with active HCV infection who are currently on treatment must have an undetectable HCV viral load, with testing performed as clinically indicated
• Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at time of registration and have undetectable HIV viral load within 6 months of registration
• Participants must not have prior allogeneic bone marrow transplantation or solid organ transplant
• Participants must not have received administration of a live, attenuated vaccine (e.g., FluMist [registered trademark]) within 28 days prior to initiation of study treatment, during treatment with atezolizumab, and not plan to receive for 5 months after the last dose of atezolizumab
• Participants must not be pregnant due to the possibility of harm to the fetus. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method (with details provided as a part of the consent process) during the treatment period and for 5 months after the final dose of atezolizumab. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
• Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
• Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
Biological: Atezolizumab, Procedure: Biospecimen Collection, Drug: Carboplatin, Drug: Cisplatin, Procedure: Computed Tomography, Drug: Etoposide, Procedure: Magnetic Resonance Imaging, Other: Patient Observation
Advanced Extrapulmonary Neuroendocrine Carcinoma, Metastatic Extrapulmonary Neuroendocrine Carcinoma, Recurrent Extrapulmonary Neuroendocrine Carcinoma, Unresectable Extrapulmonary Neuroendocrine Carcinoma
UT Southwestern
Two Studies for Patients With Unfavorable Intermediate Risk Prostate Cancer Testing Less Intense Treatment for Patients With a Low Gene Risk Score and Testing a More Intense Treatment for Patients With a Higher Gene Risk Score
This phase III trial uses the Decipher risk score to guide intensification (for higher Decipher gene risk) or de-intensification (for low Decipher gene risk) of treatment to better match therapies to an individual patient's cancer aggressiveness. The Decipher risk score evaluates a prostate cancer tumor for its potential for spreading. In patients with low risk scores, this trial compares radiation therapy alone to the usual treatment of radiation therapy and hormone therapy (androgen deprivation therapy). Radiation therapy uses high energy x-rays or particles to kill tumor cells and shrink tumors. Androgen deprivation therapy blocks the production or interferes with the action of male sex hormones such as testosterone, which plays a role in prostate cancer development. Giving radiation treatment alone may be the same as the usual approach in controlling the cancer and preventing it from spreading, while avoiding the side effects associated with hormonal therapy. In patients with higher Decipher gene risk, this trial compares the addition of darolutamide to usual treatment radiation therapy and hormone therapy, to usual treatment. Darolutamide blocks the actions of the androgens (e.g. testosterone) in the tumor cells and in the body. The addition of darolutamide to the usual treatment may better control the cancer and prevent it from spreading.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Neil Desai
161725
Male
18 Years and over
Phase 3
NCT05050084
STU-2021-1091
Inclusion Criteria:
• Pathologically (histologically or cytologically) proven diagnosis of adenocarcinoma of the prostate within 270 days prior to registration
• Unfavorable intermediate risk prostate cancer, defined as having ALL the following bulleted criteria:
• Has at least one intermediate risk factor (IRF):
• PSA 10-20 ng/mL
• Clinical stage T2b-c (digital rectal examination [DRE] and/or imaging) by American Joint Committee on Cancer (AJCC) 8th edition
• Gleason score 7 (Gleason 3+4 or 4+3 [ International Society of Urological Pathology (ISUP) Grade Group 2-3])
• Has ONE or more of the following 'unfavorable' intermediate-risk designators:
• > 1 immature reticulocyte fraction (IRF)
• Gleason 4+3=7 (ISUP Grade Group 3)
• >= 50% of biopsy cores positive
• Biopsies may include 'sextant' sampling of right/left regions of the prostate, often labeled base, mid-gland and apex. All such 'sextant' biopsy cores should be counted. Men may also undergo 'targeted' sampling of prostate lesions (guided by MRI, ultrasound or other approaches). A targeted lesion that is biopsied more than once and demonstrates cancer (regardless of number of targeted cores involved) should count as a single additional positive core sampled and positive. In cases of uncertainty, count the biopsy sampling as sextant core(s)
• Absence of high-risk features
• Appropriate stage for study entry based on the following diagnostic workup:
• History/physical examination within 120 days prior to registration;
• Negative bone imaging (M0) within 120 days prior to registration; Note: Tc-99m bone scan or sodium fluoride (NaF) positron emission tomography (PET) are allowed. Equivocal bone scan findings are allowed if plain films X-ray, computed tomography (CT) or magnetic resonance imaging (MRI) are negative for metastasis at the concerned site(s). While a negative fluciclovine, choline, or prostate specific membrane antigen (PSMA) PET may be counted as acceptable substitute for bone imaging, any suspicious findings must be confirmed and correlated with conventional imaging (Tc-99m bone scan, NaF PET, CT, X-ray, or MRI) to determine eligibility based on the latter modalities (e.g. M0 based on conventional imaging modalities)
• Clinically negative lymph nodes (N0) as established by conventional imaging (pelvic +/- abdominal CT or MR), within 120 days prior to registration. Patients with lymph nodes equivocal or questionable by imaging are eligible if the nodes are =< 1.0 cm in short axis and/or if biopsy is negative. Note: While a negative fluciclovine, choline, or prostate specific membrane antigen (PSMA) PET may be counted as acceptable substitute for pelvic imaging, any suspicious findings must be confirmed by conventional imaging (CT, MRI or biopsy). If the findings do not meet pathological criteria based on the latter modalities (e.g. node =< 10 mm in short axis, negative biopsy), the patient will still be eligible
• Age >= 18
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 120 days prior to registration
• Non-castrate testosterone level (> 50 ng/dL) within 120 days prior to registration
• Absolute neutrophil >= 1,000 cells/mm^3 (within 120 days prior to registration)
• Hemoglobin >= 8.0 g/dL, independent of transfusion and/or growth factors (within 120 days prior to registration)
• Platelet count >= 100,000 cells/mm^3 independent of transfusion and/or growth factors (within 120 days prior to registration)
• Creatinine clearance (CrCl) >= 30 mL/min estimated by Cockcroft-Gault equation (within 120 days prior to registration)
• For African American patients specifically whose renal function is not considered adequate by the formula above, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) should be used for calculating the related estimated glomerular filtration rate (GFR) with a correction factor for African American race creatinine clearance for trial eligibility, where GFR >= 30 mL/min/1.73m^2 will be considered adequate
• Total bilirubin: 1.5 =< institutional upper limit of normal (ULN) (within 120 days prior to registration) (Note: In subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin. If direct bilirubin is less than or equal to 1.5 x ULN, subject is eligible)
• Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]): =< 2.5 x institutional ULN (within 120 days prior to registration)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial; Note: HIV testing is not required for eligibility for this protocol
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B)
• For 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
• Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
Exclusion Criteria:
• Previous radical surgery (prostatectomy) or any form of curative-intent ablation whether focal or whole-gland (e.g., cryosurgery, high intensity focused ultrasound [HIFU], laser thermal ablation, etc.) for prostate cancer
• Definitive clinical or radiologic evidence of metastatic disease (M1)
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years. History of or current diagnosis of hematologic malignancy is not allowed
• Prior radiotherapy to the prostate/pelvis region that would result in overlap of radiation therapy fields
• Previous bilateral orchiectomy
• Previous hormonal therapy, such as luteinizing hormone-releasing hormone (LHRH) agonists (e.g., leuprolide, goserelin, buserelin, triptorelin) or LHRH antagonist (e.g. degarelix), anti-androgens (e.g., flutamide, bicalutamide, cyproterone acetate). ADT started prior to study registration is not allowed
• Prior use of 5-alpha-reductase inhibitors is allowed, however, it must be stopped prior to enrollment on the study with at least a 30 day washout period before baseline study PSA measure and registration
• Active testosterone replacement therapy; any replacement therapy must be stopped at least 30 days prior to registration
• Severe, active co-morbidity defined as follows:
• Current severe or unstable angina;
• New York Heart Association Functional Classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)
• History of any condition that in the opinion of the investigator, would preclude participation in this study
• Inability to swallow oral pills
• High risk features, which includes any of the following:
• Gleason 8-10 [ISUP Grade Group 4-5]
• PSA > 20
• cT3-4 by digital exam OR gross extra-prostatic extension on imaging [indeterminate MRI evidence will not count and the patient will be eligible]
Drug: Bicalutamide, Drug: Buserelin, Drug: Darolutamide, Drug: Degarelix, Drug: Flutamide, Drug: Goserelin, Drug: Histrelin, Drug: Leuprolide, Radiation: Radiation Therapy, Drug: Relugolix, Drug: Triptorelin
Prostate Adenocarcinoma, Prostate
UT Southwestern; Parkland Health & Hospital System
Elucidating the Neurocircuitry of Irritability With High-Field Neuroimaging to Identify Novel Therapeutic Targets (UNIKET)
The study is investigating dysfunctions in neurocircuitry in regards to irritability with healthy controls (HC) and individuals with Major Depressive Disorder (MDD) by performing MRIs. The MDD group will also be randomized to receive ketamine or midazolam to investigate changes post-treatment in neurocircuitry with regards to irritability.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Ann.House@UTSouthwestern.edu
Manish Jha
103647
All
18 Years to 65 Years old
Phase 2
NCT05046184
STU-2021-0667
Inclusion Criteria:
• Male or female subjects, 18-65 years of age and body weight less than or equal to 120 kg on baseline visit.
• Participants must have a level of understanding of the English language sufficient to agree to all tests and examinations required by the study and must be able to participate fully in the informed consent process.
• For Healthy Controls: Subjects must be free of any lifetime psychiatric condition based on the Mini-International Neuropsychiatric Interview (MINI). For MDD: Subjects must meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for current unipolar depression [major depressive disorder (MDD) or persistent depressive disorder (PDD) in a current major depressive episode (MDE)] based on MINI.
• A woman of childbearing potential who is sexually active with a male must agree to use an acceptable method of contraception [defined as either one highly effective (permanent sterilization, intrauterine device or hormonal implant) or two other forms of contraception (such as oral contraceptive pill and condom)] to avoid pregnancy throughout the study. Throughout the study and for 90 days (one spermatogenesis cycle) after receiving the last dose of study drug (ketamine/midazolam) man who is sexually active with a woman of childbearing potential must use an acceptable method of contraception (described above) with his female partner and must agree not to donate sperm.
• Subjects must either be free of psychotropic medications (including antidepressants, antipsychotics, benzodiazepines, mood stabilizers, sedative/hypnotics, dopamine agonists, stimulants, buspirone, and triptans) and certain anticonvulsants (topiramate and levetiracetam) or be stable on these medications for four weeks prior to the baseline visit [first magnetic resonance imaging (MRI) scan].
• Subjects with MDD should be willing to participate in neuroimaging scans before and after infusions, and be willing to undergo infusions with study drug.
Exclusion Criteria:
• Lifetime diagnosis of schizophrenia or any psychotic disorder, bipolar disorder, pervasive developmental disorder or intellectual development disorder.
• Current diagnosis of obsessive-compulsive disorder, anorexia nervosa or bulimia. Comorbid anxiety, stress and trauma-related disorders are permitted as long as unipolar depression is the primary diagnosis.
• Diagnosis of a moderate or severe substance use disorder within the past 6 months per MINI; all subjects must have a negative urine toxicology test on the day of the MRI, prior to the scan.
• Female subjects who are pregnant, nursing, for may become pregnant. Women of childbearing potential must have a negative urine pregnancy test on the day of the fMRI, prior to scan, and on days of study drug infusion, prior to infusion.
• Any unstable medical illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, immunologic, or hematologic disease.
• Inadequately treated obstructive sleep apnea (STOP-Bang score of 5-8 if untreated, if using positive airway pressure device then past-month apnea hypopnea index ≥ 15 per hour representing moderate or higher severity).
• Presence of a significant neurological disease such as Parkinson's disease, primary or secondary seizure disorders, intracranial tumors, or severe head trauma.
• Presence of neurocognitive or dementing disorders.
• Clinically significant abnormalities of laboratories, physical examination (including unstable hypertension - systolic blood pressure >170, diastolic blood pressure >100), or electrocardiogram at screening visit.
• Subjects judged to be at serious and imminent suicidal or homicidal risk by the PI or another study-affiliated psychiatrist.
• Any contraindications to MRI, including pacemakers or metallic objects in the body.
• Any claustrophobia or other conditions which may result in inability to lie still in the MRI scanner for 1 hour or more.
• Allergy to ketamine or midazolam in subjects with MDD.
• Must not be on any prohibited concomitant medication.
Drug: Ketamine Hydrochloride, Drug: Midazolam injection
Major Depressive Disorder, Psychiatric Disorders, Healthy Controls
major depressive disorder, MDD, depression, depressive disorder, depression symptoms, healthy controls, irritability, ketamine
UT Southwestern
Intraventricular Administration of Rhenium-186 NanoLiposome for Leptomeningeal Metastases (ReSPECT-LM)
This is an open-label Phase I clinical study that will administer a single dose of 186RNL via intraventricular catheter for treatment of Leptomeningeal Metastases (LM).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Michael Youssef
200728
All
18 Years and over
Phase 1
NCT05034497
STU-2021-0950
Inclusion Criteria:
• At least 18 years of age at time of screening.
• Ability to understand the purposes and risks of the study and has signed a written informed consent document approved by the site-specific IRB.
• Subject has proven and documented LM that meets the requirements for the study: a. Current EANO-ESMO Clinical Practice Guidelines Type 1 and 2 LM of any primary type. 2D is excluded.
• Karnofsky performance status of 60 to 100.
• Acceptable liver function:
• Bilirubin 1.5 times upper limit of normal
• AST (SGOT) and ALT (SGPT) ≤ 3.0 times upper limit of normal for subjects with normal liver
• AST (SGOT) and ALT (SGPT) ≤ 5.0 times upper limit of normal for subjects with liver metastasis
• Acceptable renal function with serum creatinine ≤ 2 times upper limit of normal
• Acceptable hematologic status (without hematologic support):
• ANC ≥ 1000 cells µL
• Platelet count ≥ 75,000/µL
• Hemoglobin ≥ 9.0 g/dL
• All women of childbearing potential must have a negative serum pregnancy test at screening. Male and female subjects must agree to use effective means of contraception (for example, surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose.
• Subjects with a creatinine clearance greater than or equal to 60 mL/min (using the Cockcroft-Gault Equation) for males and females.
Exclusion Criteria:
• The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v5.0) Grade ≤ 1 from AEs due to antineoplastic agents, investigational drugs, or other medications that were administered prior to study. Prior AEs due to alopecia, anemia, and lymphopenia are not required to be recovered to Grade ≤ 1 prior to 186RNL treatment, assuming other inclusion criteria are satisfied.
• Obstructive or symptomatic communicating hydrocephalus.
• Ventriculo-peritoneal or ventriculo-atrial shunts without programable valves or contraindications to placement of Ommaya reservoir.
• Females of childbearing potential who are pregnant, breast feeding, or may possibly be pregnant without a negative serum pregnancy test (see inclusion criteria).
• Serious intercurrent illness, such as progressive systemic (extra leptomeningeal) disease, clinically significant cardiac arrhythmias, uncontrolled systemic infection, symptomatic congestive heart failure or unstable angina pectoris within 3 months prior study drug, myocardial infarction, stroke, transient ischemic attack within 6 months, seizure disorder with any seizure occurring within 14 days prior to consenting or encephalopathy.
• Active severe non hematologic organ toxicity such as renal, cardiac, hepatic, pulmonary, or gastrointestinal systemic toxicity grade 3 or above.
• Significant coagulation abnormalities such as inherited bleeding diathesis or acquired coagulopathy with unacceptable risks of bleeding.
• Patients who had any dose to the spinal cord or whole brain radiation therapy, regardless of when the radiation treatment was delivered. Prior, non-CNS radiation for primary tumor is allowed.
• Systemic chemotherapeutic agents with CNS penetration (such as temozolomide, carmustine, lomustine, capecitabine, carboplatin, vinorelbine, bevacizumab, irinotecan or topotecan) are excluded if given within 14 days or 5 half-lives, whichever is shorter, prior to 186RNL treatment.
• If the washout period is satisfied, the patient may be enrolled, providing all other I/E criteria are satisfied.
• If the patient is undergoing systemic chemotherapy with CNS penetration (such as temozolomide, carmustine, lomustine, capecitabine, carboplatin, vinorelbine, bevacizumab, irinotecan or topotecan) and they develop or have progressive/persistent LM while on the agent, they may be included in the trial at the PI's discretion.
• Systemic therapy (including investigational agents and small-molecule kinase inhibitors) is excluded if given within 14 days or 5 half-lives, whichever is shorter, prior to 186RNL treatment. a. If the washout period is satisfied, the patient may be enrolled, providing all other I/E criteria are satisfied.
• Nitrosoureas or mitomycin C within 42 days, or metronomic/protracted low-dose chemotherapy within 14 days, or other cytotoxic chemotherapy within 28 days, are excluded if given within the above timepoints prior to 186RNL treatment. a. If the washout period is satisfied, the patient may be enrolled, providing all other I/E criteria are satisfied.
• Impaired CSF Flow Study, within 4 +/- 3 days of 186RNL treatment, based on study imaging and as determined by the investigator.
Drug: 186RNL
Brain and Nervous System, Leptomeningeal Metastasis
UT Southwestern
Effect of SGLT2i on Cardiovascular Biomarkers in Patients With Type 2 Diabetes and CKD Stage 3b-4
This is a prospective, observational study to assess the effect of SGLT2 inhibitors on surrogate markers of kidney and cardiovascular health in patients with stage 3b and 4 chronic kidney disease (CKD). This study includes three clinic in person visits and weekly telephone visits for 12 weeks. 1. Recruit 28 patients with CKD stages 3b-4 and follow up for 12 weeks 2. Determine the effect of interventions on the primary outcome variable serum klotho measured by immunoprecipitation-immunoblot
Call 214-648-5005
studyfinder@utsouthwestern.edu, ZHENGNAN.WANG@UTSouthwestern.edu
Robert Toto
17371
All
18 Years to 80 Years old
Phase 1
NCT05033054
STU-2021-0492
Inclusion Criteria:
• 18-80 years of age
• All races and ethnicities
• All genders
• Type 2 diabetes mellitus
• History of hypertension defined as > 130 or > 80 mmHg or normotensive on pharmacologic therapy
• Estimated glomerular filtration rate (GFR) (CKD Epi equation) of 15-44 ml/min/1.73 m2 (Stages 3b-4 CKD)
• Urinary albumin creatinine ratio of > 200 mg/g <5000mg/g
• Ability of study participant or legally authorized representative to provide informed written consent
• Able to maintain stable dose of any vitamin D and any calcium supplements for 180 days post randomization.
Exclusion Criteria:
• Autosomal dominant or autosomal recessive polycystic kidney disease, lupus nephritis or anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis
• Receiving cytotoxic therapy, immunosuppressive therapy or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment
• History of organ transplantation
• Receiving therapy with a sodium glucose co-transporter 2 (SGLT2) inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor
• Type 1 diabetes (T1D)
• Active use of SGLT2 inhibitor
• History of persistent hypercalcemia (serum total Calcium > 10.5 mg/dl)
• Body mass index > 45 kg/m2
• Active on kidney transplant list
• Inability to provide informed consent
• Any condition outside the renal and cardiovascular disease area, such as but not limited to malignancy, with a life expectancy of less than 2 years based on investigator´s clinical judgement
• Active malignancy requiring treatment at the time of screening (with the exception of successfully treated basal cell or treated squamous cell carcinoma).
• Hepatic impairment (aspartate transaminase [AST] or alanine transaminase [ALT] >3x the upper limit of normal [ULN]; or total bilirubin >2x ULN at time of enrolment)
• Women of child-bearing potential (ie, those who are not chemically or surgically sterilized or who are not post-menopausal) who are not willing to use a medically accepted method of contraception that is considered reliable in the judgment of the investigator or women who have a positive pregnancy test at enrolment or randomization or women who are breast-feeding
• Participation in another clinical study with an investigational product (IP) during the last month prior to Enrolment
• Inability of the patient, in the opinion of the investigator, to understand and/or comply with procedures and/or follow-up OR any conditions that, in the opinion of the investigator, may render the patient unable to complete the study. Patients who cannot complete the patient reported outcome (PRO) assessments can still participate in the study
Drug: SGLT2 inhibitor
Diabetes, Kidney Disease, Chronic
UT Southwestern; Parkland Health & Hospital System
CD40 Agonist, Flt3 Ligand, and Chemotherapy in Triple Negative Breast Cancer
This research study is being done to find out if the immunotherapy drugs called CDX-301 and CDX-1140 in combination with the standard chemotherapy treatment pegylated liposomal doxorubicin (PLD, Doxil) are safe and effective at controlling the cancer in patients with metastatic triple negative breast cancer, and to determine a safe dose and treatment schedule of the three drugs. This research study will also test how these treatments improve your body's immune response against the cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Sangeetha Reddy
188773
All
18 Years to 99 Years old
Phase 1
NCT05029999
STU-2021-0657
Inclusion Criteria:
• Unresectable Stage III or Stage IV Triple Negative Breast cancer
• Age 18 years or older
• Performance status ECOG 0-2
• Life expectancy ≥ 12 weeks
• Documented progressive disease, based on radiographic, clinical or pathologic assessment, during or subsequent to last anticancer therapy. Patients who need to change systemic therapy for other indications such as toxicity that are otherwise eligible for this study may enroll with approval of the lead principal investigator.
• For initial safety cohort, subject is in second to third line setting of treatment for metastatic or unresectable disease, and have received 1 to 2 prior regimens for metastatic or unresectable disease. For dose expansion, subject is in first to third line setting of treatment for metastatic or unresectable disease, and have received 0 to 2 prior regimens for metastatic or unresectable disease.
• Among any patient enrolled in the first line treatment setting, subjects must be PD-L1 negative by 22C3 assay and not be eligible for FDA approved standard of care chemotherapy and anti-PD-1/PD-L1 combination therapy as alternative to this clinical trial.
• Screening laboratory values must meet the following criteria:
• Neutrophils ≥ 1500/uL
• Platelets ≥ 100 x10(9)/L
• Hemoglobin ≥ 8 g/dL Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.
• Creatinine ≤ 2 mg/dL
• Creatinine clearance >30 mL/minute
• AST ≤ 2.5 X ULN without, and ≤ 5 x ULN with hepatic metastasis
• ALT ≤ 2.5 X ULN without, and ≤ 5 x ULN with hepatic metastasis
• Total Bilirubin ≤ 1.5 X ULN (except patients with Gilbert's syndrome or liver involvement, who must have a total bilirubin ≤ 2 X ULN)
• Alkaline phosphatase ≤ 2.5 X ULN without, and ≤ 5 x ULN with hepatic metastasis
• All men as well as women of child bearing potential enrolled in this trial must agree to use effective contraception during the course of the trial and for at least 6 months after discontinuing study treatment. Patients and/or partners who are surgically sterile or postmenopausal are exempt from this requirement.
• A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: ( 1) has not undergone a hysterectomy or bilateral oophorectomy OR (2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Provision of consent for pre-treatment and on-treatment biopsies. Biopsy sites must be soft tissue tumor lesions or accessible visceral diseases that can be biopsied with acceptable clinical risk (as judged by the investigator); are large enough to allow for the collection of tumor tissue for proposed correlative studies (e.g., anticipated goal of 6-8 cores preferred when feasible using a ≥ 18 gauge needle with an expected core sample length of 5 mm); and have not been irradiated prior to entry. This does not include bone lesions. This may exclude many lung lesions and small lesions.
• Measurable disease allowing for serial assessment of at least one target lesion(s) by RECIST 1.1 criteria [100]. Target lesions selected for tumor measurements should be those where additional (e.g., palliative) treatments are not indicated or anticipated.
• All residual toxicity related to prior anticancer therapies (excluding alopecia, grade 2 fatigue, vitiligo, endocrinopathies on stable replacement therapy, grade 2 neuropathy from taxanes or platinum and grade 2 hearing loss from platinum) must resolve to grade 1 severity or less (or returned to baseline) prior to receipt of study treatment.
• Read, understood, and provided written informed consent, and if applicable, Health Insurance Portability and Accountability Act (HIPAA) authorization, after the nature of the study has been fully explained, and must be willing to comply with all study requirements and procedures.
Exclusion Criteria:
• Among any patients enrolled in the first line treatment setting, tumors should not be PD-L1+ by 22C3 assays or eligible for FDA approved standard of care chemotherapy and anti-PD-1/PD-L1 combination therapy as alternative to this clinical trial.
• History of severe hypersensitivity reactions to mAbs.
• Prior treatment with any anti-CD40 antibody or rhuFlt3L product.
• Treatment with anthracycline in the metastatic setting.
• Prior progression while on anthracycline based therapy or within 6 months of completing (neo)adjuvant anthracycline.
• Prior history of acute myeloid leukemia (AML), or tumor with known Flt3 mutation/amplification
• Receipt of any antibody targeting T cell check point or co-stimulation pathways within 4 weeks, use of any other monoclonal based therapies within 4 weeks, and all other immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) within 2 weeks prior to the planned start of study treatment.
• Prior T-cell or other cell-based therapies within 12 weeks (or 2 weeks if patient experienced disease progression on the prior treatment)
• Systemic radiation therapy within 4 weeks, prior focal radiotherapy within 2 weeks, or radiopharmaceuticals (strontium, samarium) within 8 weeks prior to the first dose of study treatment.
• Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to the planned start of study treatment.
• Any kinase inhibitors within 2 weeks prior to the first dose of study treatment.
• Major surgery within 4 weeks prior to the first dose of study treatment. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before study drug administration and patients should be recovered.
• Use of other investigational drugs within 4 weeks or 5 half-lives (whichever is longer) prior to study treatment administration.
• Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within 2 weeks prior to first dose of study treatment. Topical, inhaled or intranasal corticosteroids (with minimal systemic absorption) may be continued if the patient is on a stable dose. Non-absorbed intraarticular corticosteroid and replacement steroids (≤ 10 mg/day prednisone or equivalent) will be permitted.
• Other prior malignancy, except for adequately treated basal or squamous cell skin cancer or in situ cancers; or any other cancer from which the patient has been disease-free for at least 3 years.
• Active, untreated central nervous system metastases.
• Patients with known treated brain metastases should be neurologically stable for 4 weeks post-treatment and prior to study enrollment. Continued use of steroids and/or anticonvulsants (in the absence of any suspicion of progressive brain metastases) is acceptable if ≤ equivalent of prednisone 10 mg daily. Brain MRI required on screening to document lack of progression.
• Women who are pregnant or nursing. All female patients with reproductive potential must have a negative pregnancy test prior to starting treatment.
• Active autoimmune disease or history of autoimmune disease or syndrome that required systemic steroids or immunosuppressive medications within the preceding 6 months, except for patients with vitiligo, endocrinopathies, or type 1 diabetes, Patients with mild asthma who require intermittent use of bronchodilators (such as albuterol) who have not been hospitalized for asthma in the preceding 6 months will not be excluded from this study.
• Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension or arrhythmia, congestive heart failure (New York Heart Association Class III or IV or EF<50%) related to primary cardiac disease, uncontrolled ischemic or severe valvular heart disease or any of the following within 6 months prior to the first dose of study treatment: myocardial infarction, severe/unstable angina, coronary artery bypass graft, congestive heart failure, cerebrovascular accident, transient ischemic attack.
• Prior anthracycline therapy with a cumulative doxorubicin-equivalent dose greater than 240 mg/m2.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. The COVID-19 vaccines available in the United States are not live vaccines and are allowed if the final vaccine dose (of a regimen that requires more than 1 dose) is received at least 1 week prior to study enrollment.
• History of (non-infectious) pneumonitis or has current pneumonitis. This includes asymptomatic infiltrates on screening chest CT scan that are felt by the investigator to potentially be an inflammatory process (i.e. grade 1 pneumonitis).
• Active infection requiring systemic therapy, known HIV infection, or positive test for hepatitis B surface antigen or hepatitis C (antibody screen and if positive confirmed by RNA analysis). If positive results are not indicative of a true active or chronic infection, the patient can be enrolled after discussion with and agreement by the Investigator.
• Any other acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with trial participation or trial drug administration or could interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into the trial.
• Evidence of acute or chronic infection on screening chest radiography.
Drug: PLD Chemotherapy, Drug: CDX-1140, Drug: CDX-301
Metastatic Triple Negative Breast Cancer, Breast - Female, Breast - Male
UT Southwestern; Parkland Health & Hospital System
Safety and Efficacy of Atorvastatin v. Placebo on HCC Risk (TORCH)
Prospective randomized, multi-center, double blind placebo-controlled trial to assess the chemopreventive impact of atorvastatin (20 mg oral) vs placebo in up to 60 adults with advanced fibrosis at high risk of developing HCC.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yujin Hoshida
183525
All
18 Years and over
Phase 2
NCT05028829
STU-2022-0471
Inclusion Criteria:
• Willing and able to provide informed consent
• Male or female age > 18 years at time of consent
• Clinically or histologically diagnosed advanced liver fibrosis or cirrhosis, as defined by one or more of the following:
• Liver biopsy demonstrating advanced fibrosis or cirrhosis (METAVIR 3-4)
• Fibroscan or MR elastography consistent with advanced fibrosis or cirrhosis
• Imaging showing cirrhotic-appearing liver with signs of portal hypertension
• Advanced fibrosis or cirrhosis documented clinically by a treating physician
• High-risk for HCC at screening according to the FIB-4 index
• High PLSec score measured in screening blood sample from the FIB-4-high individuals.
• Liver imaging within 6 months of Day 1 is required in cirrhotic subjects only, to exclude HCC
• Female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
• Willing and able to undergo protocol blood sampling
• Subject must be able to comply with dosing instructions for study drug administration and able to complete study schedule of assessments
Exclusion Criteria:
• Diagnosis of any of the following forms of chronic liver disease:
• primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), Autoimmune hepatitis, alpha-1-antitrypsin (A1AT) deficiency, Wilson disease, hemochromatosis, iron overload, prior known or suspected drug-induced liver injury (DILI)
• Current or prior history of any of the following:
• Clinically significant illness or any other major medical disorder that in the opinion of the investigator, may interfere with subject treatment, assessment or compliance with the protocol
• Known positivity for HIV infection
• Active, untreated HCV infection
• Patients with prior history of HCV who achieved sustained virologic response (SVR) >12 from Day 1 may be included in the study
• Uncontrolled chronic HBV
• Patients with well controlled disease with >12 months of stable medication use (or no medication use, in those persons for whom anti-HBV therapy is not indicated)
• Clinical hepatic decompensation, defined as Child's Pugh class B or C cirrhosis (see
• History of biliary diversion
• Solid organ transplant
• Malignancy within the 5 years prior to screening, with the exception of specific cancers that have been cured by surgical resection (basal cell skin cancer, etc). Subjects under evaluation for possible malignancy are not eligible
• Pregnant or Nursing Females (a negative serum pregnancy test is required at screening for WOCBP)
• Life threatening SAE during the screening period
• Subjects having the following laboratory parameters at screening
• ALT > 10 x ULN
• AST > 10 x ULN
• Hemoglobin < 8.5 g/dl
• Serum creatinine > 2.0 mg/dL
• CK > 3x ULN
• Females who may wish to become pregnant and/or plan to undergo egg harvesting during the study and up to 30 days of the last dose of study drug
• WOCBP must abstain from breastfeeding and be willing to use effective birth control during through the week 4 post treatment follow-up visit
• Clinically relevant alcohol or drug abuse within 12 months of screening
• Use of any prohibited concomitant medications as described in Section 9.1.1
• Use of a statin medication within 90 days of Day 1 visit
• Subjects who are on a current statin at time of consent must be willing to undergo a 90-day washout period prior to randomization
• Known hypersensitivity to Atorvastatin
• Current or planned participation in an investigational new drug (IND) trial from 30-days prior to randomization through the week 4 post treatment follow-up visit
Drug: Atorvastatin 20mg, Drug: Placebo
Cirrhosis, Liver, Liver Fibroses
Liver Disease, Chemoprevention, HCC, Atorvastatin
UT Southwestern
A Comparison of TULSA Procedure vs. Radical Prostatectomy in Participants With Localized Prostate Cancer (CAPTAIN)
Men with localized, intermediate risk prostate cancer will be randomized to undergo either radical prostatectomy or the TULSA procedure, with a follow-up of 10 years in this multi-centered randomized control trial. This study will determine whether the TULSA procedure is as effective and more safe compared to radical prostatectomy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Xiaosong Meng
189616
Male
40 Years to 80 Years old
N/A
NCT05027477
STU-2021-0564
Inclusion Criteria:
• Male
• Age 40 to 80 years, with >10 years life expectancy
• NCCN (favorable and unfavourable) intermediate-risk prostate cancer on biopsy acquired within last 12 months
• Stage ≤cT2c, N0, M0
• ISUP Grade Group 2 or 3 disease on TRUS-guided biopsy or in-bore biopsy
• PSA ≤20ng/mL within last 3 months
• Treatment-naïve
• Planned ablation volume is < 3 cm axial radius from urethra on mpMRI acquired within last 6 months
Exclusion Criteria:
• Inability to undergo MRI or general anesthesia
• Suspected tumor is > 30 mm from the prostatic urethra
• Prostate calcifications > 3 mm in maximum extent obstructing ablation of tumor
• Unresolved urinary tract infection or prostatitis
• History of proctitis, bladder stones, hematuria, history of acute urinary retention, severe neurogenic bladder
• Artificial urinary sphincter, penile implant, or intraprostatic implant
• Patients who are otherwise not deemed candidates for radical prostatectomy
• Inability or unwillingness to provide informed consent
• History of anal or rectal fibrosis or stenosis, or urethral stenosis, or other abnormality challenging insertion of devices
Device: Radical Prostatectomy, Device: TULSA Procedure
Prostate Cancer, Prostate Adenocarcinoma
Prostate ablation, high intensity transurethral ultrasound ablation, MRI-guided, minimally invasive, real-time temperature feedback control, prostate cancer, TULSA, radical prostatectomy
UT Southwestern
Durvalumab (MEDI4736) and Tremelimumab for Hepatocellular Carcinoma in Patients Listed for a Liver Transplant
Immunotherapy can safely downstage patients and achieve durable systemic disease control to improve clinical outcomes in HCC patients undergoing liver transplant.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Nicole Rich
126654
All
18 Years and over
Phase 2
NCT05027425
STU-2022-0746
Inclusion Criteria:
• Hepatocellular carcinoma, diagnosed either by biopsy or by combination of cirrhosis and imaging criteria (contrast-enhanced CT or MRI).
• Tumor within UCSF criteria for transplant: either one lesion ≤6.5 cm; or up to 3 lesions, none >4.5 cm, with a total diameter ≤8 cm, with no vascular invasion and no evidence of extrahepatic disease.
• Patient evaluated by institutional Liver Transplant team and listed for transplant.
• At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion (TL) at baseline. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to randomization.
• No prior therapy for HCC at any time.
• Age ≥18 years at the time of study entry.
• ECOG score of 0 or 1
• Child-Pugh Score of 5, 6, or 7
• Body weight >30 kg
• Patients must have adequate organ and marrow function as defined in protocol
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
Exclusion Criteria:
• Extrahepatic disease.
• Variceal bleeding during 3 months prior to registration.
• Any autoimmune disease deemed a risk in the setting of immunotherapy per treating physician's judgment.
• Any other illness or patient condition deemed a medical or logistical barrier for protocol therapy per treating physician's judgment.
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• Participation in another clinical study with an investigational product during the last 12 months Patients who have received other investigational agents previously who are no longer receiving these investigational agents may be eligible at the discretion of the PI.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• History of allogenic organ transplantation.
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician
• Patients with celiac disease controlled by diet alone
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
• History of leptomeningeal carcinomatosis
• History of active primary immunodeficiency
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
• Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine while receiving IP and up to 30 days after the last dose of IP.
• Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of durvalumab + tremelimumab combination therapy.
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
• Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment.
• Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.
Drug: Durvalumab, Drug: Tremelimumab, Procedure: Liver Transplant
Hepatocellular Carcinoma, Cirrhosis, Portal Hypertension, Liver
Transplant
UT Southwestern
An Open-Label Study of Oral NNZ-2591 in Pitt Hopkins Syndrome (PTHS-001) (PTHS-001)
A study of the safety, tolerability and pharmacokinetics of NNZ-2591 and measures of efficacy in children and adolescents with Pitt Hopkins Syndrome.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Elaine.Most@UTSouthwestern.edu
Patricia Evans
20096
All
3 Years to 17 Years old
Phase 2
NCT05025332
STU-2021-1045
Inclusion Criteria:
• Clinical diagnosis of PTHS with a documented disease-causing genetic etiology for the disorder.
• Males or females aged 3-17 years.
• Body weight of 12kg or higher at screening
• Subjects with a Clinical Global Impression- Severity (CGI-S) score of 4 or greater at the Screening visit.
• Not actively undergoing regression or loss of skills, defined as no persistent loss of previously acquired developmental skills for a period within 3 months of the Screening visit
• Each subject must be able to swallow the study medication provided as a liquid solution.
• Caregiver(s) must have sufficient English language skills.
Exclusion Criteria:
• Body weight <12kg at screening
• Clinically significant abnormalities in safety laboratory tests and vital signs at Screening.
• Abnormal QTcF interval or prolongation at Screening.
• Any other clinically significant finding on ECG at the Screening visit.
• Positive for severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) and previous COVID 19 infection with last 12 months that required hospitalization.
• Unstable or changes Psychotropic treatment 2 weeks prior to screening
• Excluded concomitant treatments.
• Actively undergoing regression or loss of skills.
• Unstable seizure profile.
• Current clinically significant renal conditions and abnormalities
• Current clinically significant cardiovascular, hepatic, gastrointestinal, respiratory, endocrine disease, or clinically significant organ impairment.
• Current clinically significant hypo- or hyperthyroidism, Type 1 or Type 2 diabetes mellitus requiring insulin (whether well controlled or uncontrolled), or uncontrolled Type 1 or Type 2 diabetes.
• Has planned surgery during the study.
• History of, or current, cerebrovascular disease or brain trauma.
• History of, or current catatonia or catatonia-like symptoms.
• History of, or current, malignancy.
• Current major or persistent depressive disorder (including bipolar depression).
• Significant, uncorrected visual or uncorrected hearing impairment.
• Allergy to strawberry.
• Positive pregnancy test
• Subject is judged by the Investigator or Medical Monitor to be inappropriate for the study
Drug: NNZ-2591
Brain and Nervous System, Pitt Hopkins Syndrome
Pitt Hopkins Syndrome
UT Southwestern; Children’s Health
NP-G2-044 as Monotherapy and Combination Therapy in Patients With Advanced or Metastatic Solid Tumor Malignancies
Multicenter, open-label study in patients with advanced or metastatic solid tumor malignancies to evaluate the safety, tolerability, and preliminary anti-tumor efficacy, PK, and pharmacodynamics of continuously dosed NP-G2-044 monotherapy and NP-G2-044 in combination with anti-PD-1 therapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Sanjay Chandrasekaran
202923
All
18 Years and over
Phase 1/Phase 2
NCT05023486
STU-2022-0778
Inclusion Criteria:
• Male or female ≥18 years of age;
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
• Able to swallow capsules;
• Adequate organ and bone marrow function, defined by the following: ANC >1500 cells/μL; Hemoglobin >9.0 g/dL; Platelet count >100,000 cells/μL; Total bilirubin ≤1.5 mg/dL; Albumin ≥3.0 g/dL; Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase ≤2.5 × upper limit of normal (ULN); Creatinine clearance ≥50 mL/min/1.73 m2; and Prothrombin time and partial thromboplastin time ≤1.5 × ULN.
• Female patients of childbearing potential must have a negative serum or urine pregnancy test at Screening and within 72 hours before the first dose of NP-G2-044. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required and must be negative for the patient to be eligible; Note: A woman is considered to be childbearing potential unless she is postmenopausal (≥1 year without menses and confirmed with a follicle-stimulating hormone [FSH] test) or surgically sterilized via bilateral oophorectomy, hysterectomy, bilateral tubal ligation, or successful Essure® placement with a documented confirmation test at least 3 months after the procedure.
• Male patients must be surgically sterile or willing to use a highly effective double-barrier contraception method (eg, male condom with diaphragm or male condom with cervical cap) upon study entry, while on NP-G2-044, and for a period of at least 4 months following the last dose of NP-G2-044; and
• Able to understand and voluntarily sign a written informed consent form (ICF) and willing and able to comply with protocol requirements. Inclusion Criteria for NP-G2-044 Monotherapy: Patients must meet all the following criteria to receive NP-G2-044 monotherapy in the study:
• Have a histopathologically confirmed advanced or metastatic solid tumor malignancy that is either treatment-refractory or otherwise ineligible for treatment with standard of care agents/regimens; and
• Have measurable disease per RECIST 1.1.; and
• For monotherapy expansion cohort (after the Mono-RP2D has been identified), patients must have:
• Gynecologic malignancies including ovarian, endometrial/uterine, fallopian tube, cervical, vulvar, and vaginal cancers; or
• Epidermal growth factor receptor (EGFR)-high (2+ or 3+ staining per DAKO criteria or genomic sequencing data showing 3 or more copies of the EGFR gene) triple-negative breast cancer (TNBC). Inclusion Criterion for NP-G2-044 Combination Therapy Patients must meet the following criterion to receive NP-G2-044 in combination with anti-PD-1 therapy in the study:
• Have initiated anti-PD-1 therapy in accordance with the package insert and have been receiving the anti-PD-1 therapy for ≥3 months (with therapy currently ongoing) and have stable disease, or had an initial period of stable disease and now have an initial scan demonstrating progressive disease per RECIST 1.1.
Exclusion Criteria:
• Received chemotherapy or radiotherapy within 4 weeks or 5 half-lives, whichever is shorter, of the first dose of NP-G2-044; Note: Prior immunotherapy is allowed for patients receiving NP-G2-044 monotherapy.
• Unresolved toxicities from previous anti-cancer therapy, defined as toxicities (other than NCI CTCAE v5.0 Grade ≤2 alopecia or neuropathy) not yet resolved to NCI CTCAE v5.0 Grade ≤1; Note: Patients who experienced a Grade ≥3 anti-PD-1-related AE per NCI CTCAE v5.0 are excluded unless recovered and reviewed by the Novita Medical Monitor or designee.
• Receiving any other investigational agent(s) or have received an investigational agent within 4 weeks of the first dose of NP-G2-044;
• Known untreated brain metastases or treated brain metastases that have not been radiographically and clinically stable (ie, not requiring steroids) ≥4 weeks prior to study enrollment;
• QTc by Fridericia method >470 msec or electrocardiogram (ECG) with evidence of clinically meaningful conduction abnormalities or active ischemia as determined by the Investigator;
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, hypertension, unstable angina pectoris, cardiac arrhythmia, autoimmune or inflammatory diseases, or psychiatric illness/social situations that would limit compliance with study requirements;
• Pregnant, lactating, or is planning to attempt to become pregnant or impregnate someone during the study or within 90 days after dosing of NP-G2-044;
• Received prior allogenic hematopoietic stem cell transplantation or allogenic bone marrow transplantation;
• Received prior solid organ transplantation;
• Ongoing immunosuppressive therapy (≥10 mg/day of prednisone or its equivalent);
• Requires the use of a strong inhibitor or inducer of cytochrome P450 (CYP)3A4, CYP1A2, or CYP2D6 during the study;
• History of clinically meaningful gastrointestinal bleeding, intestinal obstruction, or gastrointestinal perforation within 6 months of study enrollment; or
• Excluded by the Sponsor due to medical history, physical examination findings, clinical laboratory results, prior medications, or other entrance criteria.
Drug: NP-G2-044 Monotherapy, Drug: Anti-PD-1 Therapy, Drug: NP-G2-044 Combination therapy
Breast - Female, Cervix, Other Female Genital, Advanced or Metastatic Solid Tumor Malignancies
Advanced or Metastatic Solid Tumor Malignancies
UT Southwestern
Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy for Metastatic Cervical Cancer
To improve overall survival in patients with metastatic cervical cancer by loco-regional therapy with personalized ultra-fractionated radiation
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kevin Albuquerque
125449
Female
18 Years and over
Phase 2
NCT05021237
STU-2021-0787
Inclusion Criteria:
• At least 18 years of age.
• Ability to understand and the willingness to sign a written informed consent.
• Newly diagnosed FIGO IVB cervical cancer with radiographic evidence of metastatic disease for whom systemic therapy is standard of care, who are within 6 months of systemic therapy treatment, OR
• Patients with recurrent/metastatic disease with measurable disease in the pelvis for whom systemic therapy is standard of care, and who are within 6 months of initiation of systemic therapy.
• Patients with brain metastasis are allowed as long as they are clinically stable and/or the mets are treated or are amenable to treatment with radiation and/or surgery.
• Eastern Cooperative Group (ECOG) performance status of 0-3.
• Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) starting with the first radiation pulse through 90 days after the last fraction of radiation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Medically acceptable birth control (contraceptives) includes: 1) approved hormonal contraceptives (such as birth control pills, patch or ring; Depo-Provera, Implanon), or 2) barrier methods (such as a condom or diaphragm) used with a spermicide (a substance that kills sperm). A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
Exclusion Criteria:
• Prior radiation treatment to the pelvis.
• Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
• Patients with active Inflammatory Bowel disease or Collagen vascular disease -SLE, scleroderma or on active immunosuppressant (exclusions per PI discretion).
• 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.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Presence of brain metastases that are not amenable to treatment with radiation or surgery, or brain metastasis leading to clinical instability.
Radiation: Ultra-fractionated radiation therapy
Cervical Cancer, Cervix, Stage IV Cervical Cancer FIGO 2018, Adenosquamous Carcinoma of Cervix, Metastasis
Cervix
UT Southwestern; Parkland Health & Hospital System
A Randomized, Controlled Trial to Evaluate the Safety and Effectiveness of the Route 92 Medical Reperfusion System (SUMMIT MAX)
The SUMMIT MAX study is a prospective, randomized, controlled, interventional clinical trial to evaluate the safety and effectiveness of the Route 92 Medical MonoPoint® Reperfusion System for aspiration thrombectomy in acute ischemic stroke patients.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Vida.Rhodes@UTSouthwestern.edu
Roberta Novakovic
83353
All
18 Years to 85 Years old
N/A
NCT05018650
STU-2022-0053
Inclusion Criteria:
• The consent process has been completed and documented according to applicable country regulations and as approved by the IRB / Ethics Committee
• Age >=18 years and <= 85
• Patient presenting with clinical signs consistent with an acute ischemic stroke
• Baseline National Institutes of Health Stroke Scale (NIHSS) score >= 6
• Pre-stroke modified Rankin Score (mRS) <= 1
• Baseline ASPECTS >= 6
• Endovascular treatment initiated (defined as time of first angiogram) within 8 hours from time last known well
• If indicated, thrombolytic therapy shall be initiated per clinical guidelines. If eligible for thrombolytic therapy, subjects should be treated as soon as possible and lytic use should not be delayed regardless of potential eligibility for mechanical neurothrombectomy.
• The patient is indicated for aspiration neurothrombectomy with the Route 92 Medical Reperfusion System as determined by the Investigator
• Angiographic confirmation of a large vessel occlusion of the M1 segment of the middle cerebral artery or distal internal carotid artery
Exclusion Criteria:
• Known pregnancy or breast feeding
• In the Investigator's opinion, any known comorbidity (including COVID-19 positivity) that may complicate treatment or prevent improvement or follow-up
• Known serious, advanced, or terminal illness with anticipated life expectancy < 12 months
• Known history of severe allergy to contrast medium
• Known to have suffered a stroke in the past 90 days
• Known connective tissue disorder affecting the arteries (e.g. Marfan syndrome, Ehlers-Danlos syndrome)
• Any known previous cerebral hemorrhagic event
• Any known pre-existing coagulation deficiency
• Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR >3.0
• Known baseline platelet count <50,000/µL
• Known baseline blood glucose of <50 mg/dL or >400 mg/dL
• Known to be participating in another study involving an investigational device or drug
• Clinical symptoms suggestive of bilateral stroke or stroke in multiple territories.
• Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) evidence of recent/ fresh cerebral hemorrhage (the presence of microbleeds is allowed)
• Baseline CT or MRI showing intracranial tumor (except small meningioma <= 2cm) or significant mass effect with midline shift due to the tumor
• Presumed septic thrombus, or suspicion of bacterial endocarditis
• Inability to access the cerebral vasculature in the opinion of the neurointerventional team
• Unlikely to be available for a 90-day follow-up (e.g. no fixed home address)
• Evidence of carotid dissection
• Evidence of cervical carotid artery high-grade stenosis or occlusion (i.e., tandem occlusion)
• Active or recent history of drug abuse (within last 6 months)
• Known history or presence of aneurysm or arteriovenous malformation (AVM) in the territory of the target lesion
• For all patients, severe sustained hypertension with SBP >200 and/or DBP >120; for patients treated with IV tPA, sustained hypertension despite treatment with SBP >185 and/or DBP >110
• Treatment with heparin within 48 hours with a partial thromboplastic time more than two times the laboratory normal
• Renal failure with serum creatinine >3.0 or Glomerular Filtration Rate (GFR) <30
• Ongoing seizure due to stroke
• Evidence of active systemic infection
• Known cancer with metastases
• Cervical carotid stenosis requiring balloon angioplasty or stenting at the time of the procedure
• Angiographic evidence of multiple cerebrovascular occlusions (e.g., bilateral anterior circulation, anterior/posterior circulation)
• Angiographic evidence of known or suspected underlying intracranial vasculopathy or atherosclerotic lesions responsible for the target occlusion
• Angiographic evidence or suspicion of aortic dissection
Device: Route 92 Medical Reperfusion System
Acute Ischemic Stroke, Brain and Nervous System
UT Southwestern
A Study of Intravesical Enfortumab Vedotin For Treatment of Patients With Non-muscle Invasive Bladder Cancer (NMIBC)
This study will test a drug called enfortumab vedotin in participants with a type of bladder cancer called non-muscle invasive bladder cancer (NMIBC). This study will also evaluate what the side effects are and if the drug works to treat NMIBC. A side effect is anything a drug does to your body besides treating your disease. In this study enfortumab vedotin will be put into the bladder using a catheter. A catheter is a thin tube that can be put into your bladder.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yair Lotan
59883
All
18 Years and over
Phase 1
NCT05014139
STU-2021-0778
Inclusion Criteria:
• Histologically confirmed, non-muscle invasive urothelial carcinoma with carcinoma in situ (CIS) (with or without papillary disease)
• Predominant histologic component (>50 percent) must be urothelial (transitional cell) carcinoma
• Participants must have high-risk Bacillus Calmette-Guerin (BCG) - unresponsive disease, defined as (where adequate BCG therapy is defined as one of the following: 5 of 6 doses of an initial induction course + at least 2 of 3 doses maintenance therapy or 5 of 6 doses of an initial induction course + at least 2 of 6 doses of a second induction course):
• Persistent or recurrent CIS alone or with recurrent Ta/T1 (noninvasive papillary disease/tumor invades the subepithelial connective tissue) disease within 12 months of completion of adequate BCG therapy.
• Recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG therapy, or
• T1 high-grade disease at the first evaluation following an induction BCG course (at least 5 or 6 doses)
• Participant must be ineligible for or refusing a radical cystectomy
• All visible papillary Ta/T1 tumors must be completely resected within 60 days prior to enrollment.
• Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2.
Exclusion Criteria:
• Current or prior history of muscle-invasive urothelial carcinoma or metastatic disease.
• Nodal or metastatic disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) within 3 months prior to study treatment
• Concomitant upper tract urothelial carcinoma as noted on CT or MRI urogram performed within 3 months prior to study treatment
• Prior or concomitant urothelial carcinoma of the prostatic urethra within 6 months prior to study treatment
• Participants with tumor-related hydronephrosis
• Participant has received other systemic anticancer therapy including chemotherapy, biologic therapy, immunotherapy, targeted therapy, endocrine therapy, and/or investigational agent within 4 weeks or intravesical therapy within 6 weeks of first dose of study treatment
• Participant has had any prior radiation to the bladder for urothelial cancer
Drug: Enfortumab vedotin
Urinary Bladder Neoplasms, Carcinoma In Situ, Urinary Bladder, Non-muscle Invasive Bladder Cancer, Carcinoma Transitional Cell, NMIBC
Bladder Cancer, Urothelial Cancer, Enfortumab vedotin, PADCEV, Pharmacokinetics
UT Southwestern
Study of Zirconium Zr 89 Crefmirlimab Berdoxam PET/CT in Subjects With Advanced or Metastatic Malignancies (iPREDICT)
The purpose of this study is to evaluate whether zirconium Zr 89 crefmirlimab berdoxam (other names 89Zr-crefmirlimab berdoxam, 89Zr-Df-crefmirlimab, 89Zr-Df-IAB22M2C) PET/CT can predict the response of advanced or metastatic melanoma, Merkel cell carcinoma, renal cell carcinoma, or non-small cell lung cancer tumors to immuno-oncology therapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
James Brugarolas
80679
All
18 Years and over
Phase 2
NCT05013099
STU-2022-0390
Inclusion Criteria:
• Subjects will be eligible for enrollment in the study if they meet ONE criteria a, b or c in point 1 and ALL the criteria in points 2-9.
• Subjects must meet ONE of the criteria a, b or c below:
• For enrollment into Cohort A: Subjects with histologically confirmed advanced or metastatic non-uveal/non-mucosal melanoma or merkel cell carcinoma (MCPyV positive and negative) who are not amenable to surgical cure and are candidates to receive single- or combined IOT alone (not to include cytotoxic chemotherapy) as first or second line treatment.
• For enrollment into Cohort B: Subjects with histologically confirmed advanced or metastatic clear cell Renal Cell Carcinoma or Renal Cell Carcinoma with sarcomatoid features (regardless of subtype) as defined on pathologic examination by a component of clear cell or sarcomatoid, who are not amenable to surgical cure and are candidates to receive single- or combined IOT alone or IOT in combination with VEGFR-directed or tyrosine kinase inhibitor (not to include cytotoxic chemotherapy) as first or second line treatment
• For enrollment into Cohort C: Subjects with histologically confirmed advanced or metastatic non-small cell lung cancer without non-smoker/driver mutations who are not amenable to surgical cure, and are candidates to receive single- or combined IOT alone (not to include cytotoxic chemotherapy) as first or second line treatment as per the label/prescribing information at the physicians discretion. i. Patients with driver mutations that are expected to show significant benefit from first line checkpoint inhibiter treatment (such as KRAS G12C mutations) are eligible if all other I/E criteria are met Subjects must meet All of the criteria 2-9 below:
• At least 1 RECIST 1.1-measurable. non-irradiated, non-osseous (unless there is an associated measurable soft-tissue component) lesion documented on intravenous (IV) contrast-enhanced CT or MRI (per RECIST criteria 1.1) prior to first zirconium Zr 89 crefmirlimab berdoxam administration.
• Has an adequate amount of time between their prior treatment/procedure and the 1st administration of zirconium Zr 89 crefmirlimab berdoxam.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2 and anticipated survival of at least 6 months.
• Meeting all clinical safety lab values per institution's SOC, or investigator's discretion, for subjects receiving cancer treatment.
• Male or female age ≥18 years.
• Ability to understand the purposes and risks of the trial and has signed an Institutional Review Board (IRB) approved informed consent form.
• Willingness and ability to comply with all protocol required procedures.
• For men and women of child-producing potential, use of effective double barrier contraceptive methods during the study, up to 30 days after the last administration of the investigational product.
Exclusion Criteria:
• Subjects will NOT be eligible for enrollment in the study if they meet ANY of the following criteria:
• Bone-only disease without a measurable soft tissue component on conventional imaging (MRI, PET, CT).
• Subjects with skin-only (cutaneous) lesions will be excluded from the tumor biopsy assessment.
• Serious nonmalignant disease, additional active malignant disease or conditions that in the opinion of the investigator and/or ImaginAb could compromise protocol objectives.
• Subjects with splenic dysfunction or who are status post splenectomy. Post-splenectomy subjects who develop an accessory spleen with clinical and radiographic evidence of splenic function will be allowed with prior approval from the Sponsor.
• Corticosteroid therapy is prohibited if used for the treatment of inflammatory or autoimmune conditions. Patients with adrenal insufficiency from prior surgery or immunotherapy toxicity may be on standard chronic replacement doses of hydrocortisone that also require sporadic use of stress doses of steroid .
• Pregnant women or nursing mothers.
Biological: zirconium Zr 89 crefmirlimab berdoxam
Melanoma, Renal Cell Carcinoma, Non Small Cell Lung Cancer, Merkel Cell Carcinoma, Unspecified
UT Southwestern
Study of GS-1811 Given Alone or With Zimberelimab in Adults With Advanced Solid Tumors
This is a first-in-human (FIH) study to evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of GS-1811 as monotherapy and in combination with zimberelimab in participants with advanced solid tumors. This study will be conducted in 6 parts (Parts A, B, and E: monotherapy, Parts C and D: combination therapy, and Part F for both monotherapy and combination therapy) in participants with advanced solid tumors who have received, been intolerant to, or been ineligible for all treatments known to confer clinical benefit or in participants with select solid tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
177531
All
18 Years and over
Phase 1
NCT05007782
STU-2023-0042
Key
• Disease:
• Part A: Individuals with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit.
• Part B: Individuals with histologically or cytologically confirmed select indications who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit.
• Part C: Individuals with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or been ineligible for all treatments known to confer clinical benefit or whose disease is indicated for anti- programmed cell death protein 1 or programmed cell death ligand 1 (PD-[L]1) monoclonal antibody monotherapy.
• Part D: Individuals with pathologically confirmed select advanced solid tumors.
• Part E: Individuals with pathologically confirmed select advanced solid tumors. Participants must have received, have been intolerant to, or have been ineligible for all treatment known to confer clinical benefit.
• Part F: Individuals with pathologically-confirmed select advanced solid tumors. Participants must have received, have been intolerant to, or have been ineligible for all treatments known to confer clinical benefit; or, for participants who will undergo combination therapy, have disease which is indicated for anti-PD-(L)1 mAb monotherapy.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 for individuals in Parts A, B, and C, and 0 or 1 for individuals in Parts D, E, and F.
• Adequate organ function.
• Male individuals and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use methods of contraception.
• Tissue requirement:
• Parts A, C, D, E and F: Must provide pre-treatment adequate tumor tissue sample prior to enrollment.
• Part B and select participants in Parts C and F: Must have fresh pre-treatment and on-treatment biopsies for biomarker analysis. Key
• Concurrent anticancer treatment.
• Any anti-cancer therapy, whether investigational or approved, within protocol specified time prior to initiation of study including: immunotherapy or biologic therapy (< 28 days), chemotherapy (< 21 days), targeted small molecule therapy (< 14 days), hormonal therapy or other adjunctive therapy (< 14 days) or radiotherapy (< 21 days).
• Any prior CCR8 directed therapy.
• Prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation. Exception: prior corneal transplant without requirement for systemic immunosuppressive agents is allowed.
• Concurrent active malignancy other than nonmelanoma skin cancer, curatively resected carcinoma in situ, localized prostate cancer, or superficial bladder cancer after undergoing potentially curative therapy with no evidence of disease. Individuals with other previous malignancies are eligible if disease-free for > 2 years.
• History of intolerance, hypersensitivity, or treatment discontinuation due to severe immune-related adverse events (irAEs) on prior immunotherapy.
• History of autoimmune disease or active autoimmune disease requiring systemic treatment within 2 years.
• History of pneumonitis, interstitial lung disease, or severe radiation pneumonitis (excluding localized radiation pneumonitis).
• Active and clinically relevant bacterial, fungal, or viral infection that is not controlled or requires IV antibiotics.
• Active hepatitis B virus (HBV) and/or hepatitis C virus (HCV), and/or human immunodeficiency virus (HIV).
• Positive serum pregnancy test or breastfeeding female.
• Live vaccines within 30 days prior to first dose.
• Significant cardiovascular disease. Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Inclusion Criteria:
• Disease:
• Part A: Individuals with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit.
• Part B: Individuals with histologically or cytologically confirmed select indications who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit.
• Part C: Individuals with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or been ineligible for all treatments known to confer clinical benefit or whose disease is indicated for anti- programmed cell death protein 1 or programmed cell death ligand 1 (PD-[L]1) monoclonal antibody monotherapy.
• Part D: Individuals with pathologically confirmed select advanced solid tumors.
• Part E: Individuals with pathologically confirmed select advanced solid tumors. Participants must have received, have been intolerant to, or have been ineligible for all treatment known to confer clinical benefit.
• Part F: Individuals with pathologically-confirmed select advanced solid tumors. Participants must have received, have been intolerant to, or have been ineligible for all treatments known to confer clinical benefit; or, for participants who will undergo combination therapy, have disease which is indicated for anti-PD-(L)1 mAb monotherapy.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 for individuals in Parts A, B, and C, and 0 or 1 for individuals in Parts D, E, and F.
• Adequate organ function.
• Male individuals and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use methods of contraception.
• Tissue requirement:
• Parts A, C, D, E and F: Must provide pre-treatment adequate tumor tissue sample prior to enrollment.
• Part B and select participants in Parts C and F: Must have fresh pre-treatment and on-treatment biopsies for biomarker analysis. Key
Exclusion Criteria:
• Concurrent anticancer treatment.
• Any anti-cancer therapy, whether investigational or approved, within protocol specified time prior to initiation of study including: immunotherapy or biologic therapy (< 28 days), chemotherapy (< 21 days), targeted small molecule therapy (< 14 days), hormonal therapy or other adjunctive therapy (< 14 days) or radiotherapy (< 21 days).
• Any prior CCR8 directed therapy.
• Prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation. Exception: prior corneal transplant without requirement for systemic immunosuppressive agents is allowed.
• Concurrent active malignancy other than nonmelanoma skin cancer, curatively resected carcinoma in situ, localized prostate cancer, or superficial bladder cancer after undergoing potentially curative therapy with no evidence of disease. Individuals with other previous malignancies are eligible if disease-free for > 2 years.
• History of intolerance, hypersensitivity, or treatment discontinuation due to severe immune-related adverse events (irAEs) on prior immunotherapy.
• History of autoimmune disease or active autoimmune disease requiring systemic treatment within 2 years.
• History of pneumonitis, interstitial lung disease, or severe radiation pneumonitis (excluding localized radiation pneumonitis).
• Active and clinically relevant bacterial, fungal, or viral infection that is not controlled or requires IV antibiotics.
• Active hepatitis B virus (HBV) and/or hepatitis C virus (HCV), and/or human immunodeficiency virus (HIV).
• Positive serum pregnancy test or breastfeeding female.
• Live vaccines within 30 days prior to first dose.
• Significant cardiovascular disease. Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Drug: GS-1811, Drug: Zimberelimab
Advanced Solid Tumor, Colon, Lung/Thoracic, Other Digestive Organ, Rectum, Stomach, Unknown Sites
UT Southwestern
Efficacy of an m-Health Cardiac Rehabilitation Program in Heart Failure With Preserved Ejection Fraction
Heart failure (HF) portends substantial morbidity, mortality, and health care costs in the United States and the prevalence of heart failure with preserved ejection fraction (HFpEF) relative to HF with reduced ejection fraction (HFrEF) has been increasing. HFpEF is associated with a high morbidity and mortality burden and is projected to be the predominant subtype of HF in the near future. While multiple therapies have proven efficacious for patients with HFrEF, no pharmacological agents have demonstrably been shown to improve outcomes in HFpEF, highlighting the need for novel approaches to HFpEF treatment. Exercise intolerance (EI) is the cardinal symptom of HFpEF, which manifests as dyspnea and fatigue. EI leads to functional deconditioning and reduced quality of life (QOL), both of which elevate risk of death and hospitalization in patients with HFpEF. Supervised exercised training is associated with improvements in exercise capacity and QOL in adults with HFpEF. However, supervised exercise has not been widely utilized for the treatment of HFpEF due to logistical and fiscal barriers. Home-based exercise using an m-Health platform is an alternative to supervised exercise that can deliver clinician prescribed exercise interventions and wellness education though monitoring and care coordination. The goal of this study is to evaluate the feasibility and efficacy of a patient specific progressive home-based cardiac rehabilitation program leveraging the technology of the m-Health program in improving functional status, exercise capacity, and QOL in patients with HFpEF.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Vinayak.Subramanian@UTSouthwestern.edu
Ambarish Pandey
125045
All
18 Years and over
N/A
NCT05002075
STU-2021-0329
Inclusion criteria:
• Adults age> 18 years
• HFpEF with left ventricular ejection fraction >50%
• Clinically stable and no hospitalization in last 4 weeks
• Estimated glomerular filtration rate > 45 mL/min/1.73 m2 as measured by the simplified MDRD formula
• Stable diuretic regimen
• SPPB <10 or historical (within 12 months) or current Peak (measured or estimated) VO2 <= 60% predicted value for age and gender. Exclusion criteria:
• History of cancer or end stage lung disease
• Estimated glomerular filtration rate < 45 mL/min/1.73 m2 as measured by the simplified MDRD formula
• Recent HF decompensation
• Inability to do exercise test
• Inability to provide written informed consent
• History of falls
• Adults age> 18 years
• HFpEF with left ventricular ejection fraction >50%
• Clinically stable and no hospitalization in last 4 weeks
• Estimated glomerular filtration rate > 45 mL/min/1.73 m2 as measured by the simplified MDRD formula
• Stable diuretic regimen
• SPPB <10 or historical (within 12 months) or current Peak (measured or estimated) VO2 <= 60% predicted value for age and gender. Exclusion criteria:
• History of cancer or end stage lung disease
• Estimated glomerular filtration rate < 45 mL/min/1.73 m2 as measured by the simplified MDRD formula
• Recent HF decompensation
• Inability to do exercise test
• Inability to provide written informed consent
• History of falls
Other: m-health cardiac rehabilitation
Heart Failure With Preserved Ejection Fraction, Cardiovascular, Heart
HFpEF, Cardiac rehabilitation
UT Southwestern
A Study to Compare Early Use of Vinorelbine and Maintenance Therapy for Patients With High Risk Rhabdomyosarcoma
This phase III trial compares the safety and effect of adding vinorelbine to vincristine, dactinomycin, and cyclophosphamide (VAC) for the treatment of patients with high risk rhabdomyosarcoma (RMS). High risk refers to cancer that is likely to recur (come back) after treatment or spread to other parts of the body. This study will also examine if adding maintenance therapy after VAC therapy, with or without vinorelbine, will help get rid of the cancer and/or lower the chance that the cancer comes back. Vinorelbine and vincristine are in a class of medications called vinca alkaloids. They work by stopping cancer cells from growing and dividing and may kill them. Dactinomycin is a type of antibiotic that is only used in cancer chemotherapy. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill cancer cells. It may also lower the body's immune response. Vinorelbine, vincristine, dactinomycin and cyclophosphamide are chemotherapy medications that 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. This trial may have the potential to eliminate rhabdomyosarcoma for a long time or for the rest of patient's life.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Matthew Campbell
108757
All
up to 50 Years old
Phase 3
NCT04994132
STU-2021-1108
Inclusion Criteria:
• Patients must be =< 50 years of age at the time of enrollment
• Patients with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based upon institutional histopathologic classification are eligible to enroll on the study based upon stage, group, and age, as below. FOXO1 fusion status must be determined by week 4 (day 28) of therapy. RMS types included under embryonal RMS (ERMS) include those classified in the 1995 International Classification of Rhabdomyosarcoma (ICR) as ERMS (classic, spindle cell, and botryoid variants), which are reclassified in the 2020 World Health Organization (WHO) Classification as ERMS (classic, dense and botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical spindle cell ERMS variant and the newly recognized sclerosing RMS variant). Classification of alveolar RMS (ARMS) in the 2020 WHO Classification is the same as in the ICR and includes classic and solid variants
• ERMS
• Stage 4, group IV, >= 10 years of age
• ARMS
• Stage 4, group IV Patients will be eligible to remain on protocol therapy based upon stage, group, and age
• Bone marrow metastatic disease is based on morphologic evidence of RMS based on hematoxylin and eosin (H&E) stains. In the absence of morphologic evidence of marrow involvement on H&E, patients with bone marrow involvement detected ONLY by flow cytometry, reverse transcriptase (RT)-polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), or immunohistochemistry will NOT be considered to have clinical bone marrow involvement for the purposes of this study
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows (must be performed within 7 days prior to enrollment):
• Age; Maximum serum creatinine (mg/dL)
• 1 month to < 6 months; 0.4 mg/dL (male); 0.4 mg/dL (female)
• 6 months to < 1 year; 0.5 mg/dL (male); 0.5 mg/dL (female)
• 1 to < 2 years; 0.6 mg/dL (male); 0.6 mg/dL (female)
• 2 to < 6 years; 0.8 mg/dL (male); 0.8 mg/dL (female)
• 6 to < 10 years; 1 mg/dL (male); 1 mg/dL (female)
• 10 to < 13 years; 1.2 mg/dL (male); 1.2 mg/dL (female)
• 13 to < 16 years; 1.5 mg/dL (male); 1.4 mg/dL (female)
• >= 16 years; 1.7 mg/dL (male); 1.4 mg/dL (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment)
• If there is evidence of biliary obstruction by tumor, then total bilirubin must be < 3 x ULN for age
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
• Patients with evidence of uncontrolled infection are not eligible
• RMS that is considered a second malignancy and previous cancer(s) that were treated with chemotherapy and/or radiation. Surgical resection alone of previous cancer(s) is allowed
• Patients with central nervous system involvement of RMS as defined below:
• Malignant cells detected in cerebrospinal fluid
• Intra-parenchymal brain metastasis separate and distinct from primary tumor (i.e., direct extension from parameningeal primary tumors is allowed).
• Diffuse leptomeningeal disease
• Patients who have received any chemotherapy (excluding steroids) and/or radiation therapy for RMS prior to enrollment.
• Note: the following exception:
• Patients requiring emergency radiation therapy for RMS. These patients are eligible, provided they are consented to ARST2031 prior to administration of radiation
• Note: Patients who have received or are receiving chemotherapy or radiation for non-malignant conditions (e.g. autoimmune diseases) are eligible. Patients must discontinue chemotherapy for non-malignant conditions prior to starting protocol therapy
• Vincristine and vinorelbine are sensitive substrates of CYP450 3A4 isozyme. Patients must not have received drugs that are moderate to strong CYP3A4 inhibitors and inducers within 7 days prior to study enrollment
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration, Procedure: Bone Marrow Biopsy, Procedure: Bone Scan, Procedure: Computed Tomography, Drug: Cyclophosphamide, Biological: Dactinomycin, Procedure: Magnetic Resonance Imaging, Procedure: Positron Emission Tomography, Radiation: Radiation Therapy, Drug: Vincristine Sulfate, Drug: Vinorelbine Tartrate, Procedure: X-Ray Imaging
Sarcoma, Alveolar Rhabdomyosarcoma, Botryoid-Type Embryonal Rhabdomyosarcoma, Embryonal Rhabdomyosarcoma, Spindle Cell Rhabdomyosarcoma, Solid Alveolar Rhabdomyosarcoma, Spindle Cell/Sclerosing Rhabdomyosarcoma, Metastatic Embryonal Rhabdomyosarcoma, Metastatic Rhabdomyosarcoma
Children’s Health
[18F]PT2385 PET/CT in Patients With Renal Cell Carcinoma
This is an exploratory study to assess [18F]PT2385 Positron Emission Tomography/Computed Tomography (PET/CT) in patients with renal cell carcinoma (RCC). This is an open-label, nontherapeutic trial. The main objective is to correlate hypoxia-inducible factor-2alpha (HIF2α) levels as determined by an investigational [18F]PT2385 PET/CT scan with the levels on subsequently obtained tissue by HIF2α immunohistochemistry (IHC). There will be three cohorts. The first pre-surgical cohort will have [18F]PT2385 PET/CT prior to nephrectomy. The uptake and retention on Positron Emission Tomography (PET), quantified as standardized uptake value (SUV) max and mean, abbreviated SUV henceforth will be correlated with HIF2α levels by IHC on the primary tumor. The second cohort will comprise patients with metastatic clear cell renal carcinoma (ccRCC). SUV will be correlated with HIF2α levels measured by IHC on a biopsy sample from a metastasis. Both low- and high-avidity sites will be biopsied and tracer uptake correlated with HIF2α IHC. A third cohort will include patients with Von Hippel-Lindau (VHL) syndrome and any of the following disease manifestations - RCC, central nervous system (CNS) hemangioblastoma, and/or pancreatic neuroendocrine tumor(s). Investigational imaging will evaluate HIF2α expression within a tumor type and across different tumor types. A biopsy is encouraged but not mandatory for this cohort.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
James Brugarolas
80679
All
18 Years and over
Phase 1
NCT04989959
STU-2021-0592
Inclusion Criteria:
• Ability to understand and the willingness to sign a written informed consent that includes study interventions (PET/CT and, if cohort 2, mandatory biopsy).
• Ability to lie still for a 30- to 60-minute PET/CT scan.
• One of the following:
• Cohort 1. Patients with suspected RCC planned for surgery.
• Cohort 2. Patients with metastatic ccRCC or VHL syndrome and RCC. Biopsy is required (planned resection for treatment reasons of a metastatic site is acceptable in lieu of the biopsy).
• Cohort 3. Patients with VHL syndrome with RCC, CNS hemangioblastoma, and/or pancreatic neuroendocrine tumor(s) planning to start belzutifan.
• Patients with liver dysfunction will be considered "patients of special interest," and enrollment is allowed with or without criteria outlined for Cohorts 1-3. Liver dysfunction is defined clinically and is typically supported by abnormalities in imaging or laboratory studies (alanine / aspartate amino-transferase, bilirubin, alkaline phosphatase, or international normalized range (INR) for prothrombin time).
• Women of child-bearing potential must agree to undergo and have documented a negative pregnancy test on the day of [18F]PT2385 administration. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
Exclusion Criteria:
• Uncontrolled severe and irreversible intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Claustrophobia or other contraindications to PET/CT.
• Subjects must not weigh more than the maximum weight limit for the table for the PET/CT scanner where the study is being performed (>200 kilograms or 440 pounds).
• For cohort 2 patients, lack of suitable sites for mandatory biopsy. For example, patients with metastatic disease restricted to the lungs that would require percutaneous biopsies with associated risk of bleeding and pneumothorax will be excluded.
Drug: [18F]PT2385, Procedure: Positron Emission Tomography/Computed Tomography, Procedure: Biopsy
Renal Cell Carcinoma, Clear Cell Renal Cell Carcinoma, Kidney
UT Southwestern; Parkland Health & Hospital System
Investigating Medication vs. Prostatic Urethral Lift: Assessment and Comparison of Therapies for BPH (IMPACT)
This prospective, multicenter, two-arm, 1:1 randomized controlled trial (RCT) will enroll approximately 250 males at approximately 25 sites located within the United States. All enrolled subjects will be 45 years of age or older diagnosed with symptomatic benign prostatic hyperplasia (BPH). They will be randomized to one of two readily available, marketed BPH therapies; Prostatic Urethral Lift procedure with the UroLift System (PUL Arm) or 0.4mg tamsulosin HCl (MED Arm).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Catherine.Robinson@UTSouthwestern.edu
Claus Roehrborn
16184
Male
45 Years and over
Phase 4
NCT04987892
STU-2022-1058
Inclusion Criteria:
• Male 45 years of age or older
• Diagnosis of BPH
• Experiencing symptoms of BPH as indicated by an IPSS ≥8 and ≤30
• Willing to wash out of current BPH medication(s), as applicable
• An appropriate candidate for both BPH therapies evaluated in this study.
• Ability to understand and consent to participate in this study
• Willing and able to participate in follow-up evaluations
Exclusion Criteria:
• Use of alpha blocker for BPH unless washed-out for 30 days
• Use of daily phosphodiesterase type 5 inhibitor (PDE5i) for BPH unless washed-out for 30 days
• 5-alpha-reductase inhibitors for BPH used within 6 months of therapy initiation
• Current urinary tract infection or prostatitis
• Current gross hematuria
• Urinary incontinence presumed due to incompetent sphincter
• Catheter-dependent urinary retention within 1 month prior to enrollment
• Prostate volume greater than 100 cc as measured by TRUS
• Prostate specific antigen level of greater than 10 ng/ml within one year of enrollment unless prostate cancer has been ruled out
• History of neurogenic or atonic bladder
• History prostate cancer treatment
• Known to be hypersensitive to tamsulosin HCl or any component of tamsulosin HCl capsules
• Known allergy to nickel, titanium, or stainless steel
• Prior minimally invasive or surgical intervention for BPH
• Urethral conditions that may prevent insertion of delivery system into bladder.
• Currently enrolled in any other investigational clinical research trial that has not completed the primary endpoint
• History of medical, surgical or other conditions that, in the opinion of the investigator, would interfere with the treatment or evaluation of the subject
Device: UroLift System, Drug: Tamsulosin Hydrochloride
Prostate, BPH
UT Southwestern
Metabolic Remodeling in Pulmonary Arterial Hypertension (PAH)
Pulmonary arterial hypertension (PAH) is a progressive disease in which clinically relevant symptoms present a few years after the onset in rise of pulmonary arterial pressure. Increased PA pressure presents an overload on the right ventricle (RV), with RV failure being a common cause of mortality in PAH. Current therapeutic targets help reduce vascular resistance and RV afterload, however, RV dysfunction may continue to progress. Therefore, the reason for RV failure in PAH cannot be contributed to altered vascular hemodynamics alone but may be related to metabolic alterations and failure of adaptive mechanisms in the RV. Providing a better understanding of metabolic remodeling in RV failure may permit the development of RV-targeted pharmacological agents to maintain RV function despite increased pulmonary vascular pressures. This study will evaluate how cardiac metabolism changes in response to pulmonary vasodilator therapy in patients with pulmonary arterial hypertension.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Clarissa.Osagie@UTSouthwestern.edu
Kara Goss
187712
All
18 Years to 75 Years old
NCT04968210
STU-2020-1351
Inclusion Criteria:
• WHO group 1 PAH, characterized by mean pulmonary artery pressure ≥25 mmHg, PVR >3 Woods units, and pulmonary capillary wedge pressure or left ventricular end diastolic pressure ≤15 mmHg. Participants must be further classified as idiopathic PAH (IPAH) or connective tissue disease associated PAH (CTD-PAH).
• New York Heart Association (NYHA) classification I - III criteria of heart failure.
• Vasodilator therapy naïve, with the intent to initiate pulmonary vasodilator therapy.
• Age 18 - 75.
• English speaking and able to provide informed consent.
Exclusion Criteria:
• Recent syncope.
• Baseline 6MWD < 400 feet or NYHA class IV heart failure.
• Metabolic disorders such as uncontrolled diabetes (A1c > 8%) that may alter cardiac metabolism.
• Baseline use of oral steroids.
• FEV1/FVC <60%
• Contraindications to MRI, including those noted on the UTSW MRI Screening Form such as implants contraindicated at 3T, pacemakers, Implantable Cardioverter Defibrillators (ICD), or significant claustrophobia.
• Weight >210 lbs (exceeds current IND weight-based dosing guidelines) 8 . Women who are pregnant, lactating or planning on becoming pregnant during the study.
• Not suitable for study participation due to other reasons at the discretion of the investigators
Pulmonary Arterial Hypertension
UT Southwestern
Testing Combination Erdafitinib and Enfortumab Vedotin in Metastatic Bladder Cancer After Treatment With Chemotherapy and Immunotherapy
This phase Ib trial evaluates the best dose, potential benefits, and/or side effects of erdafitinib in combination with enfortumab vedotin in treating patients with bladder cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and possesses genetic alterations in FGFR2/3 genes. Erdafitinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal FGFR protein that signals cancer cells to multiply. This may help keep cancer cells from growing and may kill them. Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of cancer cells. Enfortumab attaches to a protein called nectin-4 on cancer cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Giving erdafitinib in combination with enfortumab vedotin may shrink or stabilize metastatic bladder cancer with alterations in FGFR 2/3 genes.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Waddah Arafat
183526
All
18 Years and over
Phase 1
NCT04963153
STU-2023-0272
Inclusion Criteria:
• Patients must have histologically or cytologically documented locally advanced (T4b, any N; or any T, N 2-3) or metastatic (M1, Stage IV; or metastatic recurrence after locoregional treatment) urothelial carcinoma (including renal pelvis, ureters, urinary bladder, urethra). Patients with mixed histologies are required to have a dominant transitional cell pattern
• Patients who had disease progression during or following treatment with at least one platinum-containing regimen (e.g., gemcitabine and cisplatin [GC], methotrexate, vinblastine, doxorubicin and cisplatin [MVAC], carboplatin and gemcitabine [Carbo-Gem]) and an immune checkpoint inhibitor (PD-1/ PD-L1 inhibitor including but not limited to: atezolizumab, pembrolizumab, durvalumab, avelumab, and nivolumab)
• Received a first-line platinum-containing regimen in the metastatic setting or for inoperable locally advanced disease
• Or received neo/adjuvant platinum-containing therapy for localized muscle-invasive UC, with recurrence/progression =< 12 months following completion of therapy
• Patients who received immune checkpoint inhibitor therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease either during therapy or within 12 months of therapy completion are eligible. This criterion does not apply if the checkpoint inhibitor is contraindicated
• Patients with metastatic urothelial carcinoma who are cisplatin-ineligible and progressed on upfront immune checkpoint inhibitor; or ineligible/refused immune checkpoint inhibitor therapy will be eligible for this trial
• Patient who received prior antibody drug conjugate such as sacituzumab govitecan are allowed
• Patients must have measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Previously irradiated lesions cannot be counted as target lesions unless there has been demonstrated progression in the lesion since radiotherapy and no other lesions are available for selection as target lesions
• Patients must have FGFR2/3 activating alterations identified by tumor tissue or plasma ctDNA profiling using a Clinical Laboratory Improvement Act (CLIA) certified College of American Pathologists (CAP) accredited platform
• Age >= 18 years, for ability to comply with protocol
• Because no dosing or adverse event data are currently available on the use of erdafitinib in combination with enfortumab vedotin in patients < 18 years of age, children are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Absolute neutrophil count >= 1,500/mcL (within 14 days prior to beginning trial treatment)
• Platelets >= 100,000/mcL (within 14 days prior to beginning trial treatment)
• Hemoglobin >= 9 g/dL (within 14 days prior to beginning trial treatment)
• Measured or calculated creatine clearance (CrCl) >= 30 ml/min (glomerular filtration rate [GFR] can also be used in place of creatinine CrCl) (within 14 days prior to beginning trial treatment)
• Total bilirubin =< 1.5 x ULN (institutional upper limit of normal) OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 x ULN (within 14 days prior to beginning trial treatment)
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) =<
• 5 x institutional ULN (=< 5 x ULN for subjects with liver metastasis) (within 14 days prior to beginning trial treatment)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression (CNS metastases have been clinically stable for at least 4 weeks prior to screening and baseline scans show no evidence of new or enlarged metastasis)
• Patients with a history of prostate cancer (T2NXMX or lower with Gleason score =< 7) treated with definitive intent (surgically or with radiation therapy) at least 1 year prior to study entry are eligible, provided that the subject is considered prostate cancer-free and the following criteria are met:
• Patients who have undergone radical prostatectomy must have undetectable prostate specific antigen (PSA) for > 1 year and at screening
• Patients who have had radiation must have a PSA doubling time > 1 year (based on at least 3 values determined >1 month apart) and a total PSA value that does not meet Phoenix criteria for biochemical recurrence (i.e., < 2.0 ng/mL above nadir)
• Patients with untreated low-risk prostate cancer (Gleason score =< 6) on active surveillance with PSA doubling time >1 year (based on at least 3 values determined > 1 month apart) are also eligible
• Patients who have undergone an ophthalmologic examination and have no active eye disease which would be likely to increase the risk of eye toxicity
• The effects of erdafitinib and enfortumab vedotin on the developing human fetus are unknown. For this reason and because FGFR inhibitors and humanized antibody-drug conjugate (ADC) agents are known to be teratogenic, women of child-bearing potential 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 3 months after completion of erdafitinib and enfortumab vedotin administration. 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 5 months after completion of erdafitinib and enfortumab vedotin administration
• Ability to understand and willingness to sign a written informed consent document
Exclusion Criteria:
• Patients who have had chemotherapy, targeted therapies, immunotherapy, or treatment with an investigational anticancer agent within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (including ongoing sensory or motor neuropathy of grade 2 or higher) (i.e., have residual toxicities > grade 1 or returned to baseline) with the exception of alopecia. Subjects with =< grade 2 immunotherapy- related hypothyroidism or panhypopituitarism may be enrolled when well-maintained/controlled on a stable dose of hormone replacement therapy (if indicated). Subjects with ongoing >= grade 3 immunotherapy-related hypothyroidism or panhypopituitarism are excluded. Subjects with ongoing immunotherapy related colitis, uveitis, myocarditis, or pneumonitis or subjects with other immunotherapy related adverse events (AEs) requiring high doses of steroids (> 20 mg/day of prednisone or equivalent) are excluded
• Patients who have previously received enfortumab vedotin or other MMAE-based ADCs
• Patients who have had prior treatment with an FGFR inhibitor
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to erdafitinib and enfortumab vedotin
• Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• Patients with a history of any corneal or retinal abnormality likely to increase the risk of eye toxicity
• Patients with uncontrolled intercurrent illness and currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of starting treatment. Routine antimicrobial prophylaxis is permitted
• Patients with psychiatric illness/social situations that would limit compliance with study requirements
• Subjects who have received radiotherapy within 2 weeks prior to start of treatment. Subject must have recovered adequately from the toxicity from the intervention prior to starting study treatment
• Patients with uncontrolled diabetes. Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) >= 8% or HbA1c 7% to < 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained
• Subjects who have received major surgery within 4 weeks prior to start of treatment. Subject must have recovered adequately from complications from the intervention prior to starting study treatment
• Subjects who have received a prior allogeneic stem cell or solid organ transplant
• Has persistent phosphate level > ULN during screening (within 14 days of treatment and prior to cycle 1 day 1) and despite medical management
• Has a history of or current uncontrolled cardiovascular disease including:
• Unstable angina, myocardial infarction, or known congestive heart failure class II-IV within the preceding 12 months; cerebrovascular accident or transient ischemic attack within the preceding 3 months
• Any of the following: sustained ventricular tachycardia, ventricular fibrillation, Torsades de Pointes, cardiac arrest, Mobitz II second degree heart block or third degree heart block; known presence of dilated, hypertrophic, or restrictive cardiomyopathy
• QTc prolongation as confirmed by triplicate assessment at screening (Fridericia;QTc > 480 milliseconds)
• Subjects with a history of another invasive malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Subjects with nonmelanoma skin cancer or carcinoma in situ of any type (if complete resection was performed) are allowed
Procedure: Biospecimen Collection, Procedure: Computed Tomography, Drug: Enfortumab Vedotin, Drug: Erdafitinib
Metastatic Bladder Urothelial Carcinoma, Metastatic Renal Pelvis Urothelial Carcinoma, Metastatic Ureter Urothelial Carcinoma, Metastatic Urethral Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Stage IV Bladder Cancer AJCC v8, Locally Advanced Bladder Urothelial Carcinoma, Locally Advanced Ureter Urothelial Carcinoma, Locally Advanced Urothelial Carcinoma, Stage IV Urethral Cancer AJCC v8, Locally Advanced Renal Pelvis Urothelial Carcinoma, Locally Advanced Urethral Urothelial Carcinoma, Stage IV Renal Pelvis Cancer AJCC v8, Stage IV Ureter Cancer AJCC v8, Recurrent Bladder Urothelial Carcinoma, Recurrent Renal Pelvis Urothelial Carcinoma, Recurrent Ureter Urothelial Carcinoma, Recurrent Urethral Urothelial Carcinoma, Recurrent Urothelial Carcinoma, Stage IIIB Bladder Cancer AJCC v8
UT Southwestern
Motor Network Physiology
The brain networks controlling movement are complex, involving multiple areas of the brain. Some neurological disorders, like Parkinson's disease (PD) and essential tremor (ET), cause abnormalities in these brain networks. Deep brain stimulation is a treatment that is used to treat these types of neurological diseases and is thought to help patients by modulating brain networks responsible for movement. Levodopa medication is also used to modulate this brain networks in patients with PD. The overall objective is to develop a unified theory of basal ganglia thalamocortical (BGTC) circuit dynamics that accounts for disease symptomatology, movement, and their inter-relationship. The underlying hypothesis, is that the rigidity and bradykinesia of PD are fundamentally related to excessive functional coupling across nodes in the BGTC motor circuit impeding effective information flow. In this research, the investigator will take advantage of the unique opportunity provided by awake deep brain stimulation surgery to learn more about how the brain functions in a diseased state and how deep brain stimulation changes these networks to make movement more normal. The investigator will simultaneously assess cortical and subcortical electrophysiology in relation to clinical symptoms and behavioral measures and in response to deep brain stimulation, cortical stimulation, and pharmacologic therapy in patients undergoing Deep Brain Stimulation (DBS) implantation surgery.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Sahil.Chilukuri@UTSouthwestern.edu
Nader Pouratian
205161
All
18 Years to 89 Years old
NCT04957095
STU-2021-0376
Inclusion Criteria:
• Diagnosis of Parkinson's disease or Essential Tremor who have been recommended to undergo deep brain stimulation for management of their movement disorder
• Preoperative MRI without evidence of cortical or subdural adhesions or vascular abnormalities
• Willingness and ability to cooperate during conscious operative procedure for up to 40 minutes
Exclusion Criteria:
• Patients with recent use (within one week) of anticoagulant or antiplatelet agents
• Neurocognitive testing indicating amnestic cognitive deficits
Drug: Inbrija, Other: Subcortical Stimulation
Parkinson Disease, Essential Tremor, Brain and Nervous System
deep brain stimulation, levodopa medication, motor cortex, basal ganglia, thalamus
UT Southwestern
Aging and Disease Course: Contributions to Lifespan Neurobiology of Schizophrenia
The 2020 NIMH Strategic Plan for Research calls for investigations targeting neurobiology of mental illness across the lifespan. Growing evidence suggests that lifespan neurobiology of schizophrenia (SZ) incorporates two distinct dimensions: aging and disease course. However, their clinical correlates, associated biomarker trajectories, and implications for treatment are unknown. This study will investigate differential aspects of SZ neurobiology captured by aging and disease course, in order to develop specific biomarkers which may offer actionable targets for SZ stage-dependent intervention. The study is predicated on a novel mechanistic Model of SZ Trajectories across the Adult Lifespan, positing distinct biological fingerprints within the anterior limbic system for aging and disease course in SZ: (1) alterations in the circuit's function and structure that occur earlier in the lifespan and are larger in magnitude than the alterations expected with normal aging (accelerated aging dimension); and (2) regionally-specific anterior limbic "hyperactivity" in early SZ, with a subsequent transformation into "hypoactivity" in advanced SZ (disease course dimension). In a sample of SZ and matched healthy controls (n=168, 84/group) aged 18-75 years the investigators will ascertain a broad panel of biomarkers [via multimodal brain imaging: optimized 1H-MRS, high-resolution task-based fMRI, perfusion (Vascular Space Occupancy) and structural MRI], along with comprehensive cognitive and clinical assessments. All measures will be acquired at baseline and repeated at 2-year longitudinal follow-up. Using cutting-edge computational approaches, the study will examine (i) effects of aging and SZ course on anterior limbic system biomarkers; (ii) lifespan trajectories for different biomarkers; (iii) patterns of limbic system biomarkers in age- and SZ course-based subgroups (e.g., Younger vs. Older, Early-Course vs. Advanced SZ), as well as in data-driven subgroups (e.g., those with vs. without accelerated aging profiles); and (iv) associations between biomarkers and cognitive and clinical outcomes. This research will advance the field by providing novel biomarkers that capture unique neurobiological contributions of aging and disease course in SZ, and will motivate future studies on SZ mechanisms across the lifespan and development of precision treatments.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Monserrat.Feria-Vargas@UTSouthwestern.edu
Elena Ivleva
70523
All
18 Years to 75 Years old
NCT04951700
STU-2021-0413
Inclusion Criteria:
• 18-65 years of age (SZ); 18-75 years of age (CON)
• Women and men
• All races and ethnicities
• Psychiatric diagnoses: Patient participants (SZ): Meet DSM-5 criteria for schizophrenia or schizoaffective disorder Healthy control participants (CON): No personal history of lifetime psychiatric disorders, or a family history of psychotic disorders in 1st-or 2nd- degree relatives
• Able to read, speak, and understand English
• Able and willing to provide written informed consent; and willing to commit to the study protocol, including 2-year longitudinal follow-up
Exclusion Criteria:
• Compromised cognitive function: Both SZ and CON participants: Estimated premorbid
intellectual ability <75 age-corrected score on Wide Range Achievement Test-4/Word Reading
Subtest (WRAT-4) CON participants: <26 score on the Montreal Cognitive Assessment (MoCA)
• Neurological or medical disorder that may affect brain function (history of stroke, head injury with a loss of consciousness >10 min, seizure disorder, AIDS, poorly controlled hypertension, poorly controlled diabetes, decompensated lung disease, etc.)
• Co-morbid DSM-5 diagnosis of drug/alcohol use disorder in prior 3 months
• Current treatment with benzodiazepine or non-benzodiazepine sedatives/hypnotics, and/or anticonvulsants
• Presence of ferromagnetic objects in body
• Weight or body size exceeding MRI scanner capacity [>300 lbs]
• Claustrophobia in MRI scanner
• Pregnant women
• Breastfeeding women (VASO scan will not be administered. All other imaging modalities are safe to administer.)
• Impaired kidney function: Glomerular Filtration Rate (GFR) < 30 ml/min/1.73m2 (VASO scan will not be administered due to an association between Gadolinium-based MR contrast use and Nephrogenic Systemic Fibrosis in individuals with severely impaired renal function. All other imaging modalities are safe to administer.)
• History of hypersensitivity to any MRI contrast agent (VASO scan will not be administered. All other imaging modalities are safe to administer.)
Other: Other
Schizophrenia, Aging, Disease Course, Biomarker, Neuroimaging, Cognitive Dysfunction
UT Southwestern
A Study of Seltorexant as Adjunctive Therapy to Antidepressants in Adolescents With Major Depressive Disorder Who Have an Inadequate Response to Selective Serotonin Reuptake Inhibitor (SSRI) and Psychotherapy
The purpose of this study is to assess the safety and tolerability of Seltorexant as adjunctive therapy to an antidepressant in adolescents with major depressive disorder (MDD) in the short-term compared with placebo.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Sophia.Jones@UTSouthwestern.edu
Graham Emslie
12044
All
12 Years to 17 Years old
Phase 1
NCT04951609
STU-2022-0681
Inclusion Criteria:
• Has inadequate response to trial of at least 1, but no more than 2 antidepressant treatments during the current major depressive episode including their current antidepressant fluoxetine or escitalopram (SSRI). Inadequate response is determined as less than (<) 50 percentage (%) symptom reduction after adequate antidepressant treatment for at least 6 weeks at or above the minimum therapeutic dose prior to screening
• Has had access to adequate psychotherapy in the current depressive episode (based on investigator judgement/local guidance) prior to randomization
• Must have Children's Depression Rating Scale-Revised (CDRS-R) total score greater than or equal to (>=) 48 at screening and >=40 at the baseline visit
• Participants weighing between fifth and ninety-fifth percentile for age and sex. Obese participants greater than ninety-fifth percentile and underweight participants below fifth percentile may participate following medical clearance, as long as their baseline weight is >=30 kilograms (kg)
• A female participant of childbearing potential must have a negative urine pregnancy test at screening and baseline
Exclusion Criteria:
• Has a history of liver or renal insufficiency, significant cardiac (example, congenital heart disease, cardiomyopathy, or tachyarrhythmias), vascular, pulmonary, gastrointestinal, endocrine (including uncontrolled hyperthyroidism), neurologic (including seizure disorder), hematologic, rheumatologic, psychiatric, or metabolic disturbances. Stable medical conditions are allowed
• Has current the diagnostic and statistical manual of mental disorders, fifth edition (DSM-5) diagnosis of conduct disorder, intellectual disability, autism spectrum disorder, borderline personality disorder, somatoform disorders, or fibromyalgia. A prior history of one or more of these disorders is allowed as long as the disorder(s) are currently stable and major depressive disorder (MDD) is not secondary to the original diagnosis. Has a current or prior DSM-5 diagnosis of a psychotic disorder, or bipolar disorder
• Has a significant primary sleep disorder (example, obstructive sleep apnea, parasomnias) at screening but participants with insomnia or hypersomnia disorders are allowed
• At significant risk of committing suicide based on history or according to the investigator's experience, or based on active suicidal ideation, intent or plan, item 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) within the past 3 months or a history of suicidal behavior within the last 6 months
• Has known allergies, hypersensitivity, or intolerance to seltorexant or its excipients
Drug: Seltorexant, Drug: Placebo
Depressive Disorder, Major, Psychiatric Disorders
Children’s Health
Global Linerixibat Itch Study of Efficacy and Safety in Primary Biliary Cholangitis (PBC) (GLISTEN)
This is a 2-part study in PBC participants with cholestatic pruritus and will evaluate the efficacy, safety and impact on health-related quality of life of linerixibat compared with placebo.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Uchenna.Agwunobi@UTSouthwestern.edu
Marlyn Mayo
14698
All
18 Years to 80 Years old
Phase 3
NCT04950127
STU-2021-0820
Inclusion Criteria:
• Male and female participants must be between 18 to 80 years of age inclusive, at the time of signing the informed consent.
• Participants who have documented PBC.
• Participants who have moderate to severe itch.
Exclusion Criteria:
• Symptoms suggestive of active coronavirus disease 2019 (COVID-19) infection whilst symptoms persist or known COVID-19 positive contacts within the past 14 days should be excluded for at least 14 days from the exposure.
• Total bilirubin >2.0 times Upper Limit of Normal (ULN) using the average of two Baseline measures.
• Screening Alanine Aminotransferase (ALT) > 6 times ULN in a single Baseline measure or ALT > 5 times ULN using the average of two Baseline measures.
• Screening estimated glomerular filtration rate (eGFR) <30 milliliter per minute per
• 73 square meter (mL/min/1.73m^2).
• History or presence of hepatic decompensation (e.g., variceal bleeding, hepatic encephalopathy or ascites).
• Presence of actively replicating viral hepatitis B or C (HBV, HCV) infection, primary sclerosing cholangitis (PSC), alcoholic liver disease and/or confirmed hepatocellular carcinoma or biliary cancer.
• Current clinically significant diarrhea or active inflammatory ileal disease according to Investigator´s clinical judgment.
• Current symptomatic cholelithiasis or cholecystitis.
• Current diagnosis of primary skin disorders with itch symptoms (e.g., atopic dermatitis, psoriasis).
• Primary sleep disorders such as but are not limited to sleep apnea, narcolepsy, hypersomnia.
• Current/previous diagnosis of colorectal cancer.
• Initiation, discontinuation or change in dose of ursodeoxycholic acid (UDCA), bezafibrate or fenofibrate in the 8 weeks prior to Screening.
• Use of obeticholic acid: within 8 weeks prior to Screening. (Participants may not initiate or restart during the study).
• Initiation, discontinuation, or change in dose of any of the following in the 8 weeks prior to Screening: bile acid binding resins, rifampicin, naltrexone, naloxone, nalfurafine, pregabalin, gabapentin, sertraline or other selective serotonin reuptake inhibitor (SSRIs), antihistamines used for the treatment of itching.
• Administration of any other human ileal bile acid transporter (IBAT) inhibitor in the 12 weeks prior to screening.
• Any planned procedures intended to treat cholestatic pruritus such as nasobiliary drainage or ultraviolet light therapy from Screening and throughout the study.
• History of sensitivity or intolerance to the study treatment.
Drug: Linerixibat, Drug: Placebo
Pruritus, Liver
Cholestasis, GLISTEN, GSK2330672, Itch, Primary biliary cholangitis, Pruritus
UT Southwestern