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13 Study Matches
A Clinical Study of Intismeran Autogene (V940) Treatment and Pembrolizumab in People With Bladder Cancer (V940-005/INTerpath-005)
Researchers are looking for new ways to treat people with high-risk muscle-invasive urothelial carcinoma (MIUC). Urothelial carcinoma is a type of bladder cancer that begins in cells that line the inside of the bladder and other parts of the urinary tract, such as part of the kidneys, ureters, and urethra. People with MIUC usually have chemotherapy before surgery, then surgery to remove the cancer. Chemotherapy is a type of medicine to destroy cancer cells or stop them from growing. After surgery, some people receive more treatment to prevent cancer from returning. Pembrolizumab is an immunotherapy, which is a treatment that helps the immune system fight cancer. Enfortumab vedotin (EV) is an antibody drug conjugate (ADC). An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells. Researchers want to learn if giving intismeran autogene (the study treatment) with pembrolizumab can prevent MIUC from returning after surgery. Intismeran autogene (also called mRNA-4157) is designed to treat each person's cancer by helping the person's immune system identify and kill cancer cells based on certain proteins found on those cancer cells. The goals of this study are to learn if people who receive intismeran autogene and pembrolizumab are alive and cancer free longer than those who receive placebo and pembrolizumab, and to learn about the safety of intismeran autogene, pembrolizumab, and EV, and if people tolerate them.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Waddah Arafat
ALL
18 Years to old
PHASE1
NCT06305767
STU-2024-0447
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Must provide blood samples per protocol, to enable intismeran autogene production, and circulating tumor deoxyribonucleic acid testing
* Has an Eastern Cooperative Oncology Group performance status of 0 to 2 assessed within 7 days before randomization
* Must provide a formalin-fixed paraffin-embedded tumor tissue sample for next generation sequencing
Adjuvant Cohort:
* Has MIUC
* Has dominant histology of urothelial carcinoma (UC)
* Has high-risk pathologic disease after radical resection
* For participants who have not received cisplatin-based neoadjuvant chemotherapy, are ineligible to receive cisplatin according to protocol pre-defined criteria
Perioperative Cohort:
* Has MIBC
* Has a histological diagnosis of UC
* Is deemed eligible for RC and PLND and agrees to undergo curative intent standard RC and PLND and neoadjuvant and adjuvant treatment per protocol
* Is ineligible to receive cisplatin according to protocol pre-defined criteria
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
* Has known additional malignancy that is progressing or has required active treatment ≤3 years prior to study randomization
* Has current pneumonitis/interstitial lung disease
* Has active infection requiring systemic therapy
* Has active hepatitis B and hepatitis C virus infection
Adjuvant Cohort:
* Has received prior systemic anticancer therapy
* Has received prior neoadjuvant therapy, with the exception of neoadjuvant cisplatin-based chemotherapy for MIUC
* Has severe hypersensitivity to either intismeran autogene or pembrolizumab (MK-3475) and/or any of their excipients
Perioperative Cohort:
* Has received any prior systemic treatment, cancer vaccine treatment, chemoradiation, and/or radiation therapy treatment for MIBC
* Has severe hypersensitivity to either intismeran autogene, pembrolizumab, or EV and/or any of their excipients
* Has ongoing sensory or motor neuropathy
* Has active keratitis or corneal ulcerations BIOLOGICAL: Pembrolizumab, BIOLOGICAL: Intismeran autogene, OTHER: Placebo, BIOLOGICAL: Enfortumab Vedotin, PROCEDURE: Surgery (RC plus PLND)
Bladder Cancer, Urinary Bladder
Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
UT Southwestern
A Study of LY4101174 in Participants With Recurrent, Advanced or Metastatic Solid Tumors (EXCEED)
The purpose of this study is to find out whether the study drug, LY4101174, is safe, tolerable and effective in participants with select advanced or metastatic solid tumors. The study is conducted in two parts - phase Ia (dose-escalation, dose-optimization) and phase Ib (dose-expansion). The study will last up to approximately 4 years.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years and over
PHASE1
NCT06238479
STU-2024-0162
Inclusion Criteria:
* Have one of the following solid tumor cancers:
* Cohort A1: urothelial carcinoma, triple negative breast cancer, non-small cell lung cancer, esophageal cancer, pancreatic cancer, ovarian cancer, cervical cancer (squamous cell carcinoma), head and neck squamous cell carcinoma or prostate cancer
* Cohort A2/B1/B2: urothelial carcinoma
* Cohort C1: triple negative breast cancer
* Cohort C2: non-small cell lung cancer
* Cohort C3: ovarian or fallopian tube cancer
* Cohort C4: cervical cancer
* Cohort C5: head and neck squamous cell carcinoma
* Prior Systemic Therapy Criteria:
* Cohort A1/C1-5: Individual has received all standard therapies for which the participant was deemed to be an appropriate candidate by the treating investigator; OR there is no standard therapy available for the disease. There is no restriction on number of prior therapies
* Cohort A2/B1/B2: Individual must have received at least one prior regimen in the advanced or metastatic setting. There is no restriction on number of prior therapies.
* Prior enfortumab vedotin specific requirements:
* Cohorts A1/A2/C1-5: prior treatment with enfortumab vedotin is allowed, but not required
* Cohort B1: individual must be enfortumab vedotin naive in the advanced/metastatic setting
* Cohort B2: individual must have received enfortumab vedotin in the metastatic/advanced setting.
* Measurability of disease
* Cohort A1: measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST 1.1)
* Cohorts A2, B1, B2, C1-5: measurable disease required as defined by RECIST v1.1
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Have adequate archival tumor tissue sample available or undergo a screening biopsy if allowed per country specific regulations
Exclusion Criteria:
* Individual with known or suspected uncontrolled CNS metastases
* Individual with uncontrolled hypercalcemia
* Individual with uncontrolled diabetes
* Individual with evidence of corneal keratopathy or history of corneal transplant
* Any serious unresolved toxicities from prior therapy
* Significant cardiovascular disease
* Current of history of intestinal obstruction in the previous 3 months
* Recent thromboembolic event or bleeding disorder
* Prolongation of QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 ms
* History of pneumonitis/interstitial lung disease
* History of Grade ≥3 skin toxicity when receiving enfortumab vedotin
* Individuals who are pregnant, breastfeeding or plan to breastfeed during study or within 30 days of last dose of study intervention
* Individual with active uncontrolled infection DRUG: LY4101174
Metastatic Solid Tumor, Recurrent Solid Tumor, Advanced Solid Tumor, Urinary Bladder Neoplasm, Triple Negative Breast Cancer, Non-Small Cell Lung Cancer, Esophageal Cancer, Pancreatic Cancer, Ovarian Cancer, Cervical Cancer, Head and Neck Squamous Cell Carcinoma, Prostate Cancer, Renal Pelvis Cancer, Bladder Cancer, Breast - Female, Breast - Male, Cervix, Esophagus, Larynx, Lip, Oral Cavity and Pharynx, Lung/Thoracic, Ovary, Pancreas, Prostate, Urinary Bladder
Bladder Cancer, Bladder Neoplasm, Bladder Urothelial Carcinoma, Urinary Bladder Cancer, Urinary Tract Cancer, Urothelial Neoplasms, Renal Pelvis Cancer, Ureter Cancer, Nectin-4, Antibody Drug Conjugate (ADC)
UT Southwestern
Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder for Bladder Cancer Treatment, MODERN Study
This phase II/III trial examines whether patients who have undergone surgical removal of bladder, but require an additional treatment called immunotherapy to help prevent their bladder cancer from coming back, can be identified by a blood test. Many types of tumors tend to lose cells or release different types of cellular products including their DNA which is referred to as circulating tumor DNA (ctDNA) into the bloodstream before changes can be seen on scans. Health care providers can measure the level of ctDNA in blood or other bodily fluids to determine which patients are at higher risk for disease progression or relapse. In this study, a blood test is used to measure ctDNA and see if there is still cancer somewhere in the body after surgery and if giving a treatment will help eliminate the cancer. Immunotherapy with monoclonal antibodies, such as nivolumab and relatlimab, can help the body's immune system to attack the cancer, and can interfere with the ability of tumor cells to grow and spread. This trial may help doctors determine if ctDNA measurement in blood can better identify patients that need additional treatment, if treatment with nivolumab prolongs patients' life and whether the additional immunotherapy treatment with relatlimab extends time without disease progression or prolongs life of bladder cancer patients who have undergone surgical removal of their bladder.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years and over
PHASE2
NCT05987241
STU-2024-0089
Inclusion Criteria:
* PRE-REGISTRATION: Histologically confirmed muscle-invasive urothelial carcinoma of the bladder. Variant histology, including neuroendocrine differentiation, is allowed if urothelial cancer is predominant histology (any amount of squamous differentiation is allowed provided the tumor is not a pure squamous cell cancer)
* PRE-REGISTRATION: Patient must have had radical cystectomy and lymph node dissection \>= 3 weeks, but =\< 12 weeks prior to pre-registration. Patients who have had a partial cystectomy as definitive therapy are not eligible
* PRE-REGISTRATION: No gross cancer at the surgical margins. Microscopic invasive urothelial carcinoma at the surgical margins (i.e., "positive margins") are allowed. Carcinoma in situ (CIS) at margins is considered negative margins
* PRE-REGISTRATION: No evidence of residual cancer or metastasis after cystectomy (imaging is not required prior to pre-registration but is required prior to registration)
* PRE-REGISTRATION: Have undergone a radical cystectomy with pathological evidence of urothelial carcinoma of the bladder at high risk of recurrence as described in one of the two scenarios below (i or ii). The 7th edition of American Joint Committee on Cancer (AJCC) staging will be utilized.:
* (i) Patients who have not received neoadjuvant cisplatin-based chemotherapy: pT3-pT4\* or pT0/x-pT4/N+ on cystectomy and are not eligible for adjuvant cisplatin chemotherapy
* (i) Patients ineligible for cisplatin due to at least one of the following criteria and reason for ineligibility should be documented:
* (i) Creatinine Clearance (using Cockcroft-Gault): \< 60 mL/min
* (i) Common Terminology Criteria for Adverse Events (CTCAE) version 5, grade \>= 2 audiometric hearing loss
* (i) CTCAE version 5, grade \>= 2 or above peripheral neuropathy
* New York Heart Association Class III heart failure
* (i) Eastern Cooperative Oncology Group (ECOG) performance status = 2
* (i) Patients who are eligible for cisplatin may be candidates if they refuse available adjuvant chemotherapy, despite being informed by the investigator about the treatment options. The patient's refusal must be documented.
* (i) Patients with pT2N0 urothelial cancer on cystectomy (without prior neoadjuvant chemotherapy) with ctDNA(+) Signatera results based on an assay performed post-cystectomy as part of routine care outside of the study may proceed with pre-registration but require confirmation of ctDNA(+) Signatera testing on repeat "central testing" in the context of A032103 testing. Patients with pT2N0 with central testing not confirming ctDNA(+) will not be eligible for A032103 (Note: this is distinct from patients with ypT2N0 who are eligible based on ii).
* (ii) Patients who received cisplatin-based neoadjuvant chemotherapy: ypT2-ypT4 or ypT0/x-pT4/N+ on cystectomy
* PRE-REGISTRATION: Available tumor tissue for central Signatera testing to be submitted after pre-registration. Central testing is defined as testing performed as part of the A032103 study prior to registration and is provided by the study and not routine standard commercial testing. Patients who have already had Signatera testing performed as part of routine care will require repeat central testing as part of the A032103 study to be eligible for registration/randomization. Tumor tissue from the cystectomy is preferred over tissue from prior transurethral resection
* PRE-REGISTRATION: Age \>= 18 years
* PRE-REGISTRATION: ECOG Performance Status 0-2
* PRE-REGISTRATION: Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects
* PRE-REGISTRATION: No postoperative/adjuvant systemic therapy after cystectomy
* PRE-REGISTRATION: No adjuvant radiation after cystectomy
* PRE-REGISTRATION: No treatment with any other type of investigational agent =\< 4 weeks before pre-registration
* PRE-REGISTRATION: Not have ever received prior treatment with PD-1/PD-L1 blockade.
* PRE-REGISTRATION: Not have ever received prior treatment with LAG-3 blockade.
* PRE-REGISTRATION: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* PRE-REGISTRATION: Absolute Neutrophil Count (ANC) \>= 1,200/mm\^3
* PRE-REGISTRATION: Platelet count \>= 100,000/mm\^3
* PRE-REGISTRATION: Hemoglobin \>= 8 g/dL
* PRE-REGISTRATION: Creatinine =\< 1.5 x upper limit of normal (ULN) or calculated (calc.) creatinine clearance \> 30 mL/min (using either Cockcroft-Gault formula or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
* PRE-REGISTRATION: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3 x ULN
* PRE-REGISTRATION: Total bilirubin =\< 1.5 x upper limit of normal (ULN) (except in patients with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)
* PRE-REGISTRATION: For women of childbearing potential only: A negative urine or serum pregnancy test done =\< 14 days prior to pre-registration is required
* PRE-REGISTRATION: Not currently requiring hemodialysis
* PRE-REGISTRATION: No current or prior history of myocarditis
* PRE-REGISTRATION: No active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens- Johnson syndrome, or phospholipid syndrome because of the risk of recurrence or exacerbation of disease.
* PRE-REGISTRATION: Patients with vitiligo, endocrine deficiencies including type I diabetes mellitus, thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible.
* PRE-REGISTRATION: Patients with rheumatoid arthritis and other arthropathies, Sjögren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.
* PRE-REGISTRATION: No current pneumonitis or prior history of non-infectious pneumonitis that required steroids within the previous 5 years.
* PRE-REGISTRATION: No known active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected).
* PRE-REGISTRATION: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* PRE-REGISTRATION: Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible.
* PRE-REGISTRATION: No concurrent antineoplastic therapy.
* PRE-REGISTRATION: No current immunosuppressive agents (with the exception of corticosteroids as described below).
* PRE-REGISTRATION: No condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of pre-registration (with the exception of steroid pre-medications for contrast allergies). Inhaled or topical steroids and adrenal replacement doses \< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
* REGISTRATION: Patient must have had radical cystectomy and lymph node dissection =\< 18 weeks prior to registration.
* REGISTRATION: Must have evaluable ctDNA Signatera assay result (i.e., ctDNA\[+\]or ctDNA\[-\]) based on test performed as part of central testing after pre-registration to A032103. Central testing is defined as testing performed as part of the A032103. Local/commercial testing results may not be used for registration to A032103
* Cisplatin-ineligible (or cisplatin-declining) patients with a pT2N0 urothelial cancer on cystectomy who were pre-registered based on routine standard care ctDNA(+) Signatera testing must have confirmed ctDNA(+) Signatera testing on central testing. If central Signatera testing yields a ctDNA(-) result, these patients are ineligible. NOTE: This is a distinct consideration from patients with ypT2-4 and/or ypN+ urothelial cancer (i.e., patients who had received neoadjuvant cisplatin-based chemotherapy) who are eligible with either ctDNA(+) or ctDNA(-) central Signatera testing
* REGISTRATION: All patients must have confirmed disease-free status defined as no measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, or definitive non-measurable radiographic metastatic disease, within 60 days prior to registration. Patients with equivocal nodes less than 15 mm in short axis, or \< 10 mm in long axis for non-lymph node lesions, not considered by the investigator to represent malignant disease will be eligible. Attempts should be made to resolve the etiology of equivocal lesions with complementary imaging (e.g., PET scan) or biopsy.
* REGISTRATION: No major surgery =\< 3 weeks before registration.
* REGISTRATION: No live vaccine within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette- Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist \[registered trademark\]) are live attenuated vaccines and are not allowed. Coronavirus disease 2019 (COVID-19) vaccines are not live vaccines and are allowed
* COHORT B, ARM 4 PATIENTS INITIATING NIVOLUMAB AFTER CONVERSION OF ctDNA ASSAY FROM ctDNA(-) to ctDNA (+):
* Patient must have converted to ctDNA(+) during serial monitoring performed centrally in the setting of the A032103 study
* COHORT B, ARM 4 PATIENTS INITIATING NIVOLUMAB AFTER CONVERSION OF ctDNA ASSAY FROM ctDNA(-) to ctDNA (+):
* No evidence of metastatic disease on the most recent scheduled imaging assessment as outlined in the study calendar (no repeat imaging is necessary specifically at the time of the conversion from ctDNA\[-\] to ctDNA\[+\]).
* COHORT B, ARM 4 PATIENTS INITIATING NIVOLUMAB AFTER CONVERSION OF ctDNA ASSAY FROM ctDNA(-) to ctDNA (+):
* No change in clinical condition and/or laboratory tests that would impact the safety of nivolumab in the opinion of the treating investigator
* COHORT B, ARM 4 PATIENTS INITIATING NIVOLUMAB AFTER CONVERSION OF ctDNA ASSAY FROM ctDNA(-) to ctDNA (+):
* =\< 6 weeks from reporting of ctDNA(+) result by Natera. PROCEDURE: Biospecimen Collection, OTHER: cfDNA or ctDNA Measurement, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Nivolumab, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, BIOLOGICAL: Relatlimab
Muscle Invasive Bladder Urothelial Carcinoma, Stage II Bladder Urothelial Carcinoma AJCC v6 and v7, Stage III Bladder Urothelial Carcinoma AJCC v6 and v7, Stage IV Bladder Urothelial Carcinoma AJCC v7, Urinary Bladder
UT Southwestern
FORAGER-1: A Study of LOXO-435 (LY3866288) in Participants With Cancer With a Change in a Gene Called FGFR3 (FORAGER-1)
The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435 by itself or when it is combined with other standard medicines that treat cancer. LOXO-435 may be used to treat cancer of the cells that line the urinary system and other solid tumor cancers that have a change in a particular gene (known as the FGFR3 gene). Participation could last up to 30 months (2.5 years) and possibly longer if the disease does not get worse.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years and over
PHASE1
NCT05614739
STU-2023-0080
Inclusion Criteria:
* Have solid tumor cancer with an FGFR3 pathway alteration on molecular testing in tumor or blood sample that is deemed as actionable
* Cohort A1: Presence of an alteration in FGFR3 or its ligands
* Cohort A2, B2, B3, and B5: Histological diagnosis of urothelial cancer (UC) that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration
* Cohorts B1 and B4: Histological diagnosis of urothelial cancer that is locally advanced or metastatic
* Cohort C1: Must have histological diagnosis of a non-urothelial solid tumor malignancy that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration
* Measurability of disease:
* Cohort A1 and B3: Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1)
* Cohorts A2, B1, B2, B4, B5, and C1: Measurable disease required as defined by RECIST v1.1
* Have adequate tumor tissue sample available. Participants with inadequate tissue sample availability may still be considered for enrollment upon review
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 for Cohorts A1, A2, B3, and B5
* Less than or equal to 2 for Cohorts B1, B2, B4, and C1
* Prior Systemic Therapy Criteria:
* Cohort A1/C1: Participant has received all standard therapies for which the participant was deemed to be an appropriate candidate by the treating Investigator; OR the participant is refusing the remaining most appropriate standard of care treatment; OR there is no standard therapy available for the disease. There is no restriction on number of prior therapies.
* Cohort A2, B2, B3 participants must have received at least one prior regimen, and cohorts B1 and B4 participants at least 2 prior regimens, in the locally advanced or metastatic setting
* There is no restriction on number of prior therapies
* Cohort B5: Participants have not received prior systemic therapy for locally advanced or metastatic UC
* FGFR inhibitor specific requirements:
* Cohort A1/A2/B3: Prior FGFR inhibitor treatment is permitted but not required
* Cohort B1/B4: Participants must have been previously treated with erdafitinib
* Cohort B2, B5, and C1: Participants must be FGFR inhibitor naïve
Exclusion Criteria:
* Participants with primary central nervous system (CNS) malignancy
* Untreated or uncontrolled CNS metastases
* Current evidence of corneal keratopathy or retinal disorder. Individuals with asymptomatic ophthalmic conditions may be eligible
* Any serious unresolved toxicities from prior therapy
* Significant cardiovascular disease
* Prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF)
* Active uncontrolled systemic infection or other clinically significant medical conditions
* Participants who are pregnant, lactating, or plan to breastfeed during the study or within 6 months of the last dose of study treatment. Participants who have stopped breastfeeding may be enrolled DRUG: LOXO-435, DRUG: Pembrolizumab, DRUG: enfortumab vedotin
Urinary Bladder Neoplasms, Neoplasm Metastasis, Ureteral Neoplasms, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Kaposis sarcoma, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites, Urinary Bladder
Bladder Cancer, Bladder Urothelial Carcinoma, Urinary Bladder Cancer, Urinary Tract Cancer, Renal Pelvis Cancer, Ureter Cancer
UT Southwestern; Parkland Health & Hospital System
A Study of ACR-368 in Ovarian Carcinoma, Endometrial Adenocarcinoma, and Urothelial Carcinoma
This is an open label Phase 1b/2 study to evaluate the efficacy and safety of ACR-368 as monotherapy or in combination with ultralow dose gemcitabine in participants with platinum-resistant ovarian carcinoma, endometrial adenocarcinoma, and urothelial carcinoma based on Acrivon's OncoSignature® test status.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Miller
ALL
18 Years and over
PHASE1
NCT05548296
STU-2023-0562
Inclusion Criteria:
General
• Participant must be able to give signed, written informed consent.
• Participant must have histologically confirmed, locally advanced (i.e., not amenable to curative surgery and/or radiation therapy) or metastatic cancer that has progressed during or after at least 1 prior therapeutic regimen.
• Participant must have at least 1 measurable lesion per RECIST v1.1 criteria (by local Investigator) (Eisenhauer, 2009) in a baseline tumor imaging that has been obtained within 28 days of the treatment start. Participant must have radiographic evidence of disease progression based on RECIST v1.1 criteria following the most recent line of treatment. Biochemical recurrence (eg, cancer antigen \[CA-125\] in ovarian carcinoma) only is not considered as disease progression.
• Participant must be willing to provide tissue from a newly obtained tumor biopsy from an accessible tumor lesion not previously irradiated after written informed consent. Newly obtained is defined as a specimen taken after written informed consent is obtained, during the 28-day Screening period.
• Participant must be willing to provide an archival tumor tissue block or at least 20 unstained slides, if available.
• Participant must have stabilized or recovered (Grade 1 or baseline) from all prior therapy related toxicities, except as follows:
• Alopecia is accepted.
• Endocrine events from prior immunotherapy stabilized at ≤ Grade 2 due to need for replacement therapy are accepted (including hypothyroidism, diabetes mellitus, or adrenal insufficiency).
• Neuropathy events from prior cytotoxic therapies stabilized at ≤ Grade 2 are accepted.
• Participant must have an Eastern Cooperative Oncology Group Performance Status 0 or 1.
• Participant must have an estimated life expectancy of longer than 3 months.
• Participant must have adequate organ function at Screening, defined as:
• Absolute neutrophil count \> 1500 cells/µL without growth factor support within 1 week prior to obtaining the hematology values at Screening.
• Hemoglobin ≥ 9.0 g/dL without transfusion or growth factor support within 2 weeks prior to obtaining the hematology values at Screening.
• Platelets ≥ 100,000 cells/µL without transfusion within 1 week prior to obtaining the hematology values at Screening.
• Calculated creatinine clearance ≥ 30 mL/min as calculated by the Cockcroft Gault formula.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN); ≤ 5 × ULN if liver metastases are present.
• Total bilirubin ≤ 1.5 × ULN not associated with Gilbert's syndrome. If associated with Gilbert's syndrome ≤ 3 x ULN is acceptable.
• Serum albumin ≥ 3 g/dL.
• Participant must have adequate coagulation profile as defined below if not on anticoagulation. If subject is receiving anticoagulation therapy, then subject must be on a stable dose of anticoagulation for ≥ 1 month:
• Prothrombin time within 1.5 x ULN.
• Activated partial thromboplastin time within 1.5 x ULN. Tumor Specific Inclusion Criteria For Ovarian Carcinoma:
• Participant must have histologically documented, advanced metastatic and/or unresectable) platinum resistant high-grade serous/endometrioid ovarian, primary peritoneal, or fallopian tube cancer. Platinum-resistant disease is defined as progression or relapse within 6 months after the completion of platinum-based therapy. a. Carcinosarcoma is eligible.
• Participant must have received at least 1 but no more than 6 prior lines of systemic therapy, including at least 1 line of therapy containing platinum derivative and taxane, and single-agent therapy must be appropriate as the next line of treatment:
• Participant must have had prior bevacizumab or did not receive bevacizumab based on Investigator judgment (see Section 2.1.1).
• Participants with or without documented test results assessing alterations in the DNA repair pathway genes, eg, Breast Cancer gene 1 (BRCA1), BRCA2, and homologous recombination deficiency, at Screening are eligible. Subjects with known BRCA mutated tumors should have received a PARP inhibitor maintenance or treatment.
• Participant will be enrolled regardless of tumoral folate receptor alpha (FRα) expression status. FRα expression status will be collected for retrospective analysis, if the information is available. For Endometrial Carcinoma
• Participant must have histologically documented, high-grade endometrial adenocarcinoma.
• All Grade 3 International Federation of Gynecology and Obstetrics epithelial endometrial histological subtypes are eligible including: endometrioid, serous, and clear-cell carcinoma.
• Carcinosarcoma is eligible.
• Participant must have no more than 4 prior lines of therapy in the recurrent setting, including platinum-based chemotherapy for subtypes of endometrial adenocarcinoma where it is a standard of care. The four lines of therapies must not include more than 3 lines containing a cytotoxic regimen.
• Participant must have documented failure (includes treatment discontinuation related to toxicity) or ineligibility (based on Investigator judgement) for prior anti-programmed cell death protein 1/anti-programmed death- ligand 1 (anti-PD 1/anti-PD L1) based therapy for advanced/metastatic disease. Prior combination of PD 1/PD L1 inhibitor and vascular endothelial growth factor tyrosine kinase inhibitor (TKI) is acceptable.
• Prior neoadjuvant or adjuvant chemotherapy included in initial treatment are not considered first- or later-line treatment unless such treatments were completed less than 6 months prior to the current tumor recurrence. Prior treatment may include chemotherapy, chemotherapy/radiation therapy, and/or consolidation/maintenance therapy.
• Prior treatment with hormonal therapy or inhibitors of the mTOR or CDK4/6 pathways are not considered a line of therapy in any setting. For Urothelial Carcinoma
• Participant must have histologically documented, advanced (metastatic and/or unresectable) urothelial carcinoma. Variant histology is allowed as long as the tumor is predominantly urothelial.
• Participants must have:
• Received a platinum containing regimen (cisplatin or carboplatin) in the metastatic/locally advanced, neoadjuvant, or adjuvant setting. If platinum was administered in the adjuvant/neoadjuvant setting, participant must have progressed within 12 months of completion.
• Been exposed to or have been ineligible for checkpoint inhibitors (including PD-1 or PD-L1 inhibitors).
• Been exposed to or have been ineligible for enfortumab vedotin.
Exclusion Criteria:
General
• Participant with known symptomatic brain metastases requiring \> 10 mg/day of prednisolone (or its equivalent). Participants with previously diagnosed brain metastases are eligible if they have completed their treatment, have recovered from the acute effects of radiation therapy or surgery prior to the start of ACR-368 treatment, fulfill the steroid requirement for these metastases, and are neurologically stable based on central nervous system imaging ≥ 4 weeks after treatment.
• Participant had systemic therapy or radiation therapy within 2 weeks prior to the first dose of study drug.
• Participants has known human immunodeficiency virus, hepatitis B, or hepatitis C infection that is considered uncontrolled based on the criteria included in Appendix 2.
• Participant has a history of clinically meaningful coagulopathy, bleeding diathesis.
• Participant has cardiovascular disease, defined as:
• Uncontrolled hypertension defined as blood pressure \> 160/90 mmHg at Screening confirmed by repeat (medication permitted).
• History of torsades de pointes, significant Screening electrocardiogram (ECG) abnormalities, including ventricular rhythm disturbances, unstable cardiac arrhythmia requiring medication, pathologic symptomatic bradycardia, left bundle branch block, second degree atrioventricular (AV) block type II, third degree AV block, Grade ≥ 2 bradycardia, uncorrected hypokalemia not amenable to correction, congenital long QT syndrome, prolonged QT interval due to medications, corrected QT based on Fridericia's formula (QTcF) \> 450 msec (for men) or \> 470 msec (for women).
• Symptomatic heart failure (per New York Heart Association guidelines; (Caraballo, 2019), unstable angina, myocardial infarction, severe cardiovascular disease (ejection fraction \< 20%, transient ischemic attack, or cerebrovascular accident within 6 months of Day 1).
• Participant has a history of major surgery within 4 weeks of Screening.
• Participant has a history of bowel obstruction related to the current cancer or participant has signs or symptoms of intestinal obstruction, which include nausea, vomiting, or objective radiologic finding of bowel obstruction in the last 4 weeks before the start of the treatment.
• Participant has taken a prior cell cycle CHK1 inhibitor, including ACR-368 Tumor Specific Exclusion Criteria For Ovarian Carcinoma:
• Participant has non-epithelial carcinoma, clear-cell, mucinous, germ-cell, low-grade serous, or low-grade endometrioid carcinoma.
• Participant has a history of clinically meaningful ascites, defined as a history of paracentesis or thoracentesis within 4 weeks of Screening. Participant has a planned therapeutic paracentesis or thoracentesis between Screening and Cycle 1 Day 1 dosing.
• Participant has a history of active inflammatory bowel disease within 2 years prior to Screening.
• Participant has a history of bowel perforation, fistula, necrosis, or leak within 8 weeks of Screening. For Endometrial Adenocarcinoma:
• Participant has low-grade endometrioid carcinoma.
• Participant has mesenchymal tumors of the uterus.
• Participant has a history of clinically meaningful ascites, defined as a history of paracentesis or thoracentesis within 4 weeks of Screening. Participant has a planned therapeutic paracentesis or thoracentesis between Screening and Cycle 1 Day 1 dosing. For Urothelial Carcinoma:
• Participant has sarcoma, carcinosarcoma, melanoma, or lymphoma of the bladder.
• Participant has not received a previous platinum-based regimen.
• Participant has small cell or neuroendocrine histology.
DRUG: ACR-368, DRUG: Gemcitabine, DIAGNOSTIC_TEST: OncoSignature
Platinum-resistant Ovarian Cancer, Endometrial Adenocarcinoma, Urothelial Carcinoma, Corpus Uteri, Ovary
Urothelial Carcinoma, Bladder Cancer, Urinary Bladder Neoplasm, Urologic Neoplasm, Urogenital Neoplasm, Endometrial Cancer, Endometrial Neoplasm, Ovarian Cancer, Ovarian Neoplasm, Ultralow dose gemcitabine, Platinum-resistant Ovarian Carcinoma
UT Southwestern
A Study to Evaluate Safety, Efficacy of FF-10832 in Combo With Pembrolizumab in Urothelial & Non-small Cell Lung Cancer
To confirm a recommended Phase 2 dose (RP2D) of FF-10832 (Gemcitabine Liposome Injection) given intravenously Day 1 of a 21-day cycle, in combination with 200 mg pembrolizumab given intravenously Day 1 of the same 21-day cycle, for treatment of advanced urothelial and non-small cell lung cancer
Call 833-722-6237
canceranswerline@utsouthwestern.edu
John Lohrey
ALL
18 Years and over
PHASE2
NCT05318573
STU-2023-0065
Inclusion Criteria:
• Written informed consent is provided by patient or legally acceptable representative;
• Age ≥ 18 years;
• Patient populations:
• In the Safety Run-in, patients with histologically or cytologically confirmed advanced or metastatic solid tumors who have disease progression after treatment with standard therapies for metastatic disease that are known to confer clinical benefit, or are intolerant to treatment or refuse standard treatment will be enrolled in therapy
• In Expansion Phase, patient must have urothelial or NSCLC, and have failed prior anti-PD-1 or anti-PD-L1
• Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology
• Eastern Cooperative Oncology Group performance status of 0 to 1
• Life expectancy of ≥ 3 months
Exclusion Criteria:
• Positive urine pregnancy test within 72 hours prior to treatment
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (or 5 half-lives, whichever is shorter) prior to treatment;
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137), AND was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event;
• Has received prior radiotherapy within 2 weeks of start of study treatment.
• For patients with NSCLC:
• Patients who have received radiation therapy to the lung that is \>30 Gy within 6 months of the first dose of trial treatment are excluded;
• Patients with mutations (e.g., EGFR mutations or ALK gene rearrangements) will be excluded unless they have been previously treated with all specific targeted therapies.
• Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
• Has had an allogeneic tissue /solid organ transplant.
DRUG: Pembrolizumab, DRUG: FF-10832
Advanced Urothelial Carcinoma, Advanced Non Small Cell Lung Cancer, Lung/Thoracic, Urinary Bladder
UT Southwestern
Enfortumab Vedotin and Pembrolizumab in People with Bladder Cancer
This study will test whether enfortumab vedotin combined with pembrolizumab is an effective treatment for people with bladder cancer (urothelial carcinoma) involving the lymph nodes who are going to have surgery to remove their cancer (cystectomy). The researchers will look at whether treatment with enfortumab vedotin and pembrolizumab before surgery can get rid of cancer within the lymph nodes. They will also try to find out if this combination of drugs is effective at shrinking participants' cancer before their surgery. The researchers think that a combination of enfortumab vedotin and pembrolizumab may help people with this disease because both drugs are designed to help the immune system attack and kill cancer cells. The researchers think the drugs may be more effective if given in combination rather than on their own.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years and over
PHASE2
NCT05239624
STU-2023-0105
Inclusion Criteria:
* Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of muscle invasive bladder cancer (previously known as transitional cell) carcinoma (i.e., cancer of the bladder, renal pelvis, ureter, or urethra)
* Clinical Stage T2-T4, N1-N3, M0 OR cT1, N2-N3, M0
* Pathology:
* Representative urothelial carcinoma FFPE tumor specimens (tumor blocks or 20 unstained slides). Patients with \< 20 slides may be enrolled after discussion with the principal investigator.
* Muscle invasive urothelial carcinoma of the bladder histologically confirmed at the enrolling institution from TURBT. (Urothelial carcinoma invading into the prostatic stroma with no histologic muscle invasion is allowed provided the extent of disease is confirmed via imaging and/or EUA.)
* Evidence of urothelial carcinoma from FNA of lymph node OR lymphadenopathy suspicious for nodal disease on cross-sectional imaging, MRI, or u/s.
* Node positivity for eligibility will be defined as imaging read with suspicious lymph node ≥ 1.0 cm in the short axis, with biopsy, as documented by the radiologist at the treating center. While biopsy to confirm lymph node involvement is preferred, patients without biopsy proven urothelial carcinoma in lymph nodes may be enrolled if imaging shows a lymph node ≥ 1.0 cm in the short axis, and with confirmation from the study principal investigator.
* Deemed medically appropriate for radical cystectomy with treatment response achieved, as per MSK or participating site Attending Urologic Oncologist
* Platinum eligible and ineligible patients are permitted on study
* No prior treatments for muscle invasive or metastatic urothelial carcinoma
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
* Estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73 m2 using the CKD-EPI equation: eGFR = 141 x min(Scr/k, 1)a x max (Scr/k, 1)-1.209 x 0.993Age x 1.018 \[if female\] x 1.159 \[if black\]
°Scr is serum creatinine, k is 0.7 for females and 0.9 for males, a is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/k or 1, and max indicates the maximum of Scr/k or 1
* Be willing and able to provide written informed consent for the trial
* Contraception requirements:
• Male participants: A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days following the last dose of treatment, corresponding to time needed to eliminate any study treatment(s) (e.g. 5 terminal half-lives for pembrolizumab and enfortumab vedotin) plus an additional 90 days (a spermatogenesis cycle) after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants: A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies: i. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR ii. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least \[90 days (corresponding to time needed to eliminate any study treatment(s) (pembrolizumab and enfortumab vedotin) plus 30 days (a menstruation cycle)\] after the last dose of study treatment. * Have adequate organ function as defined in the following table (Table 1). Specimens must be collected within 14 days prior to the start of study treatment either prior to consent or at the study screening visit. * Hematological * Absolute neutrophil count (ANC) ≥1500/μL * Platelets ≥100 000/μL * Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La * Renal °Measured or calculatedb creatinine clearance (GFR can also be used in place of creatinine or CrCl) GFR or CrCl of ≥ 30 mL/min * Hepatic * Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN * AST (SGOT) and ALT (SGPT) ≤ 2.5 × ULN * Coagulation °International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal. a Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks. b eGFR as calculated by the CKD-EPI equation can be used in place of the creatinine clearance Note: This table includes eligibility-defining laboratory value requirements for treatment; laboratory value requirements should be adapted according to local regulations and guidelines for the administration of specific chemotherapies
Exclusion Criteria:
* Evidence of NYHA functional class III or IV heart disease
* Any of the following within 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
* On-going cardiac dysrhythmias of NCI CTCAE Version 5.0 grade ≥ 2. However, stable atrial fibrillation controlled medically or with a device (i.e. pacemaker) or prior ablation is allowed
* Pre-existing sensory grade ≥ 2 neuropathy
* Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure aside from cystectomy during the course of the study. Transurethral resection or other urinary tract diagnostic procedures, excisional biopsy, IR-guided biopsy, or MEDIPORT placement are NOT defined as major surgical procedures.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
* A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
* Is currently enrolled in another therapeutic trial. Patients cannot receive concurrent treatment on another clinical trial; Patients are allowed to enroll on supportive care trials or non-treatment trials (e.g. QOL, dietary survey studies) concurrently
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
* Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to allocation.
* Prior treatment with an antibody drug conjugate for bladder cancer directed therapy
* Prior systemic chemotherapy (prior intravesical therapy is allowed)
* Prior radiation therapy to the bladder
* Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
* Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. 1. 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 (eg, FluMist®) are live attenuated vaccines and are not allowed. Administration of killed vaccines is allowed. COVID-19 vaccination is permitted.
°Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine (e.g., FluMist®) within 4 weeks prior to Cycle 1, Day 1 or at any time during the study.
* Has receieved intravesical bacillus Calmette-Guerin (BCG) within 4 weeks before Cycle 1, Day 1 14.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
* Has a history of poorly controlled human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) related illness. Patients with a history of an aids-defining opportunistic infection within the last 12 months or who are on prophylactic antimicrobials related to underlying HIV are not eligible. Patients with a history of HIV and a CD4 T cell count of ≥350 are eligible to enroll in this study with the approval of the study PI.
* Subjects 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.
* Has a history of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Wegener's granulomatosis, vascular thrombosis associated with antiphospholipid syndrome, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, systemic vasculitis, or glomerulonephritis.
* Patients with history of autoimmune related hypothyroidism on stable dose of thyroid replacement hormone may be eligible for this study
* Patients with controlled Type I diabetes mellitus on a stable dose of insulin may be eligible for this study
* Has a history of idiopathic pulmonary fibrosis, pneumonitis/interstitial lung disease that requires steroids or has current pneumonitis/interstitial lung disease (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan
* Patients with active hepatitis B virus (HBV, chronic or acute, defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) or hepatitis C antibody
* Patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody \[HBc Ab\] and absence of HBsAg) are eligible. HBV DNA must be obtained in these patients prior to Cycle 1, Day 1 and confirmed to be negative.
* Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
* Active tuberculosis or BCG infection
* Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
* Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1. Abnormal urinalysis does not constitute signs/symptoms of infection unless urine culture obtained at screening grows ≥ 100,000 colonies of bacteria.
* Therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1
* Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are eligible.
* Patients receiving antibiotics for active infection are not eligible
* Prior allogeneic stem cell or solid organ transplant
* AEs from prior anticancer therapy that have not resolved to Grade ≤ 1 except for alopecia
* Patients with a history of or active bone marrow disorders expected to interfere with study therapy (e.g. acute leukemias, accelerated/blast-phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma)
* Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; and inherited liver disease
* Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
* Patients with active keratitis or history of corneal ulcers are excluded
* Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
* Rash must cover less than 10% of body surface area (BSA)
* Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%)
* No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation \[PUVA\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
* Malignancies other than the disease under study within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-ofcare management (e.g. prostate cancer with Gleason score ≤ 7, and prostate-specific antigen \[PSA\] ≤ 10 mg/mL, etc). DRUG: Enfortumab vedotin, DRUG: Pembrolizumab
Urothelial Carcinoma, Gall Bladder, Urinary Bladder
Locally Advanced and/or Node Positive, Enfortumab vedotin, Pembrolizumab, Clinical Stage T2-T4, N1-N3, M0 OR cT1, N2-N3, M0, 21-316
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
ALL
18 Years and over
PHASE1
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, Carcinoma Transitional Cell, Non-muscle Invasive Bladder Cancer, NMIBC, Urinary Bladder
Bladder Cancer, Urothelial Cancer, Enfortumab vedotin, PADCEV, Pharmacokinetics
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
ALL
18 Years and over
PHASE1
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 \[SGPT\]) =\< 2.5 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
* Corrected QT interval (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: Bone Scan, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography Test, DRUG: Enfortumab Vedotin, DRUG: Erdafitinib, PROCEDURE: Multigated Acquisition Scan
Locally Advanced Bladder Urothelial Carcinoma, Locally Advanced Renal Pelvis Urothelial Carcinoma, Locally Advanced Ureter Urothelial Carcinoma, Locally Advanced Urethral Urothelial Carcinoma, Locally Advanced Urothelial Carcinoma, Metastatic Bladder Urothelial Carcinoma, Metastatic Renal Pelvis Urothelial Carcinoma, Metastatic Ureter Urothelial Carcinoma, Metastatic Urethral Urothelial Carcinoma, Metastatic Urothelial Carcinoma, 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, Stage IV Bladder Cancer AJCC v8, Stage IV Renal Pelvis Cancer AJCC v8, Stage IV Ureter Cancer AJCC v8, Stage IV Urethral Cancer AJCC v8, Gall Bladder, Other Urinary, Urinary Bladder
UT Southwestern
Gemcitabine Versus Water Irrigation in Upper Tract Urothelial Carcinoma
There is a high rate of intravesical (bladder) recurrence following extirpative surgery for upper tract urothelial carcinoma. There is no single established standard of care for prevention of intravesical recurrence; however, one protocol in common use involves the use of intravesical gemcitabine instilled into the bladder during surgery and prior to entry into the bladder. There are barriers to the use of gemcitabine, especially at lower volume centers. Some evidence suggests that intravesical irrigation with sterile water has equivalent efficacy to intravesical chemotherapy in prevention of recurrent bladder cancer following transurethral resection of bladder tumors (TURBT). This study is intended to compare recurrence rates using intravesical gemcitabine (as a pseudo-standard of care) and continuous bladder irrigation with sterile water.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yair Lotan
ALL
18 Years to 90 Years old
PHASE3
NCT04865939
STU-2021-0402
Inclusion Criteria:
* Biopsy proven UTUC with plan for excisional surgery (distal ureterectomy or nephroureterectomy) with curative intent
* Age 18 - 90 years
* Life expectancy \> 1 year
* Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
* A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
* Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
* Concurrent or prior diagnosis of bladder cancer with a disease-free interval of less than three years.
* Synchronous bilateral upper tract urothelial carcinoma (prior history of contralateral UTUC is permissible with a disease-free interval of more than three years).
* Plan for radical cystectomy.
* Small bladder capacity (\< 100 mL).
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine or other agents used in study. PROCEDURE: sterile water irrigation, DRUG: Gemcitabine
Urothelial Cancer of Renal Pelvis, Urothelial Carcinoma Ureter, Urinary Bladder
UT Southwestern
Testing the Addition of MEDI4736 (Durvalumab) to Chemotherapy Before Surgery for Patients With High-Grade Upper Urinary Tract Cancer
This phase II/III trial compares the effect of adding durvalumab to chemotherapy versus chemotherapy alone before surgery in treating patients with upper urinary tract cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as methotrexate, vinblastine, doxorubicin, cisplatin, and gemcitabine work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Durvalumab in combination with chemotherapy before surgery may enhance the shrinking of the tumor compared to chemotherapy alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Vitaly Margulis
ALL
18 Years and over
PHASE2
NCT04628767
STU-2021-0698
Inclusion Criteria:
* STEP 1 REGISTRATION AND RANDOMIZATION
* Patients must be \>= 18 years of age
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
* Patient must have a diagnosis of high grade upper tract urothelial carcinoma expected within 14 weeks (98 days) prior to registration/randomization with one of the following:
* Biopsy (gold standard, preferred) and either upper urinary tract mass on cross-sectional imaging or
* Tumor directly visualized during upper urinary tract endoscopy
* High grade cytology and clinically estimated invasive upper urinary tract mass on cross-sectional imaging (e.g., including presence of tumor-related hydronephrosis) or tumor directly visualized during upper urinary tract endoscopy
* NOTE: Universal histologic testing of UTUC with additional studies, such as immunohistochemistry or microsatellite instability, is strongly recommended to identify patients with high probability of Lynch-related or other germline mutation related cancers whom clinicians should refer for genetic counseling and germline testing (this is not required for eligibility)
* Due to the anatomy of upper urinary tract and lack of muscularis propria, pathologic evidence of cT2 on biopsy is usually not possible
* Leukocytes \>= 3,000/mcL (obtained =\< 14 days prior to registration/randomization)
* Platelets \>= 100,000/mcL (obtained =\< 14 days prior to registration/randomization)
* Total bilirubin =\< 1.2 mg/dL (or ≤ 2 mg/dLfor patients with Gilbert's disease)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2 x institutional ULN (obtained =\< 14 days prior to registration/randomization)
* Hemoglobin (Hgb) \>= 9 g/dL (obtained =\< 14 days prior to registration/randomization)
* NOTE: Packed red blood transfusion is allowed to achieve this parameter as per treating investigator
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration/randomization are eligible for this trial
* NOTE: These patients must be stable on their anti-retroviral regimen with evidence of at least two undetectable viral loads within the past 6 months on the same regimen; the most recent undetectable viral load must be within the past 12 weeks. They must have a CD4 count of greater than 250 cells/mcL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count \< 200 cells/mcL over the past 2 years, unless it was deemed related to the cancer and/or chemotherapy induced bone marrow suppression. They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months
* NOTE: For patients who have received chemotherapy in the past 6 months, a CD4 count \< 250 cells/mcL during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy. They must have an undetectable viral load and a CD4 count \>= 250 cells/mcL within 7 days of registration/randomization
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* NOTE: Testing for HIV, hepatitis B or hepatitis C is not required unless clinically indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and have undetectable viral load. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* Patient must have a body weight of \> 30 kg
* Patient must have life expectancy of \>= 12 weeks
* Patient must have creatinine clearance \> 15 ml/min as estimated by Cockcroft-Gault formula or glomerular filtration rate (GFR) \> 15 ml/min/1.73m\^2 within 28 days prior to registration/randomization
* NOTE: Patients will be assigned to cisplatin-ineligible and cisplatin-eligible cohorts based on their creatinine clearance, Eastern Cooperative Oncology Group (ECOG) performance status, and grade (if any) of peripheral neuropathy and/or hearing loss in keeping with recommended cisplatin contraindications. Patients who are cisplatin-eligible will be randomized to either Arm A or Arm B and patients who are cisplatin-ineligible will be registered to Arm C
* Patients that meet any of the following four criteria will be registered to the cisplatin-ineligible Arm C if they meet other eligibility criteria:
* Creatinine clearance \> 15 ml/min and =\< 50 ml/min (estimated by Cockcroft-Gault formula) or GFR \> 15ml/min/1.73m\^2 and ≤ 50 ml/min/1.73 m\^2
* Hearing loss \>= 3
* Neuropathy \>= 2
* ECOG performance status 2
* In addition, the patient must have an absolute neutrophil count (ANC) \>= 1,000/mcL obtained =\< 14 days prior to registration
* Patients that meet all of the following four criteria will be randomized to the cisplatin-eligible Arm A or Arm B:
* Creatinine clearance of \> 50ml/min (estimated by Cockcroft-Gault formula) or GFR \> 50ml/min/1.73m\^2
* ECOG performance status 0-1
* Hearing loss grade 0-2
* Neuropathy 0-2
* In addition, the patient must have an absolute neutrophil count (ANC) \>= 1,500/mcL obtained =\< 14 days prior to randomization
* Also, the patient must have left ventricular ejection fraction (LVEF) \>= 50% by (either multigated acquisition scan \[MUGA\] or 2-D echocardiogram) obtained within obtained within 28 days prior to randomization
Exclusion Criteria:
* Patients must not have any component of small cell/neuroendocrine carcinoma. Other histologic subtypes (variants) are permitted provided the half or predominant (\>= 50%) subtype is conventional urothelial carcinoma
* Patients must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A patient of childbearing potential is defined as any patient, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patients of childbearing potential and sexually active patients must not expect to conceive or father children, either by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of registration, while on study treatment and for at least 6 months after the last dose of protocol treatment
* Patients must have no evidence of metastatic disease or clinically enlarged regional lymph nodes (\>= 1.5 cm short axis) on imaging required within 28 days prior to registration (Non-regional findings \>=1.5 cm short axis that in the opinion of the investigator are not concerning for involvement based on radiographic characteristics, chronicity, avidity on positron emission tomography (PET) or other imaging or other criteria can be eligible based on investigator discretion).
* NOTE: Patients with elevated alkaline phosphatase, calcium or suspicious bone pain/tenderness can also undergo baseline bone scan to evaluate for bone metastasis at the discretion of local provider.
* Patient must meet below criteria for prior/current malignancy history:
* Non-urothelial cancer malignancy history:
* Patient must not have another active (or within two years) second malignancy other than resected non-melanoma skin cancers, resected in situ breast, cervical or other in situ carcinoma, and either clinically insignificant per the investigator (e.g. =\< Gleason 3+4) on active surveillance (or watchful waiting) or previously treated prostate cancer with no rising prostate specific antigen (PSA) and no plan to treat
* NOTE: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* Urothelial cancer malignancy history:
* Patient may have a history of resectable urothelial cancer as long as patients meet one of the following:
* T0, Ta or Tis at any time
* T1-4a N0 and no evidence of disease (NED) for more than 2 years from the latest therapy \[e.g., radical surgery, transurethral resection of bladder tumor (TURBT), radiation, chemotherapy (neoadjuvant or adjuvant, or with radiation)\]. Prior immune checkpoint inhibitor is not allowed.
* Patient with history of \>= pT4b, N+, and/or M1 UC is not eligible.
* NOTE: Patients in whom concomitant or prior bladder/urethra predominant (\>= 50%) urothelial carcinoma have been surgically resected and demonstrated to be only Ta or carcinoma in situ (CIS) (\< cT1 N0) are eligible regardless of time elapsed
* Patient must not have any uncontrolled illness including, but not limited to, ongoing or active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis \[TB\] testing in line with local practice), symptomatic congestive heart failure (CHF), myocardial infarction (MI) or unstable angina pectoris, significant uncontrolled cardiac arrhythmia, clinically relevant liver cirrhosis, interstitial lung disease, or psychiatric illness/social situations in the three months prior to registration that would limit compliance with study requirements
* Patient must not have received prior radiation therapy to \>= 25% of the bone marrow for other diseases
* Patient must not have received prior systemic anthracycline therapy
* NOTE: Patients who have received prior intravesical chemotherapy at any time for non-muscle invasive urothelial carcinoma of the bladder are eligible
* Patient must not have either history of or active autoimmune disease requiring immunosuppressive therapy within 2 years prior to registration/randomization or any history of inflammatory bowel disease (inflammatory bowel disease \[IBD\], e.g. ulcerative colitis, or Crohn's disease), neuromuscular autoimmune condition, immune-related pneumonitis or interstitial lung disease. Patients with well-controlled hyper/hypothyroidism, celiac controlled by diet alone, diabetes mellitus type I, vitiligo, alopecia, psoriasis, eczema, lichen planus, or similar skin/mucosa condition are eligible
* Patient must not be on or have used immunosuppressive medication within 14 days prior to the first dose of durvalumab. The following are exceptions to this criterion:
* Intranasal, inhaled, intra-auricular, 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 at the time of enrollment
* Steroids as pre-medications for hypersensitivity reactions (e.g. computed tomography \[CT\] pre-medication)
* Patient must not have received live attenuated vaccine within 30 days prior to the first dose of durvalumab, while on protocol treatment and within 30 days after the last dose of durvalumab
* Patient must not have had a major surgical procedure within 28 days prior to registration/randomization
* NOTE: Cystoscopy/ureteroscopy, stent placement or nephrostomy tube is not considered major surgery
* Patient must not have history of allogenic organ transplantation PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Doxorubicin Hydrochloride, BIOLOGICAL: Durvalumab, DRUG: Gemcitabine Hydrochloride, PROCEDURE: Magnetic Resonance Imaging, DRUG: Methotrexate, BIOLOGICAL: Pegfilgrastim, PROCEDURE: Therapeutic Conventional Surgery, DRUG: Vinblastine Sulfate
Renal Pelvis and Ureter Urothelial Carcinoma, Urinary Bladder
UT Southwestern; Parkland Health & Hospital System
Comparing the New Anti-cancer Drug Eribulin With Chemotherapy Against the Usual Chemotherapy Alone in Metastatic Urothelial Cancer
This phase III trial compares the usual chemotherapy treatment to eribulin plus gemcitabine in treating patients with urothelial cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Chemotherapy drugs, such as eribulin, gemcitabine, docetaxel, paclitaxel, and sacituzumab govitecan work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial aims to see whether adding eribulin to standard of care chemotherapy may work better in treating patients with metastatic urothelial cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
ALL
18 Years and over
PHASE3
NCT04579224
STU-2023-0199
Inclusion Criteria:
* Participant must have predominant histologically or cytologically proven urothelial carcinoma in a metastatic site
* Participant must have evidence of metastatic urothelial carcinoma based on CT or MRI within 28 days prior to registration
* Participant must have had progression of disease following prior therapy at the discretion of the treating investigator
* Participants must not require immediate central nervous system (CNS)-specific treatment, in the opinion of the treating investigator if they have active brain metastases (defined as new or progressive brain metastases) or leptomeningeal disease
* Participant must have had prior systemic therapy in metastatic setting that:
* Included enfortumab vedotin
* Included a PD1/PDL1 antibody
* NOTE: Under the discretion of the treating physician, participants who are not candidates for PD1/PDL1 antibody systemic therapy are allowed
* Any systemic therapy provided in adjuvant, neoadjuvant, or chemoradiation settings for urothelial carcinoma can be considered to be in metastatic setting, if the last day of treatment was within 12 months prior to the diagnosis of metastatic disease
* Participant must have completed any planned surgery or radiation therapy prior to registration
* Participant must not have unresolved toxicities from prior surgeries or radiation therapy \> grade 1 at the time of registration
* Participant must be ≥ 18 years of age
* Participant must have Zubrod performance status 0-2
* Participant must have history and physical examination within 28 days prior to registration
* Participant must have complete blood count (CBC), complete metabolic panel including liver function tests, and lactate dehydrogenase (LDH) obtained within 28 days prior to registration
* Participant must have adequate kidney function as evidenced by measured or calculated creatinine clearance \>= 20 mL/min within 28 days prior to registration
* Participant must have adequate hepatic function documented by either aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =\< 3 x institutional upper limit of normal (IULN) within 28 days prior to registration. If both AST and ALT are performed, both must be =\< 3 x IULN. For participants with liver metastases, AST or ALT must be =\< 5 x IULN
* Participant must be on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 6 months prior to registration if they are known to have human immunodeficiency virus (HIV)-infection
* Participants must have undetectable hepatitis B virus (HBV) viral load within 28 days prior to registration if participant has known chronic hepatitis B virus (HBV) infection
* Participants with a known history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load within 28 days prior to registration
* Participants may have a prior or concurrent malignancy provided the natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen per the opinion of the treating investigator
* Participants must not be planning to take strong or moderate CYP3A or CYP2C8 inhibitors or inducers if randomized to Arm 1 and standard of care (SOC) regimen chosen is paclitaxel or docetaxel. Participants receiving strong or moderate CYP3A- or CYP2C8 inducers must discontinue use at least 2 weeks prior to randomization
* Participant must not have a known history of corrected QT (QTc) prolongation
* Participants must not be pregnant or nursing due to the risk of harm to a fetus or nursing infant. Women and men of reproductive potential must have agreed to use an effective contraceptive method for the course of the study and 6 months (females) or 3.5 months (males) after the last dose. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate participant chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
* Participants must be offered the opportunity to participate in specimen banking as outlined
* Participants must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
* As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, DRUG: Docetaxel, DRUG: Eribulin Mesylate, DRUG: Gemcitabine Hydrochloride, PROCEDURE: Magnetic Resonance Imaging, DRUG: Paclitaxel, BIOLOGICAL: Sacituzumab Govitecan
Metastatic Bladder Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Refractory Bladder Urothelial Carcinoma, Refractory Urothelial Carcinoma, Stage IV Bladder Cancer AJCC v8, Gall Bladder, Urinary Bladder
UT Southwestern; Parkland Health & Hospital System
Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
This phase II trial studies how well cabozantinib works in combination with nivolumab and ipilimumab in treating patients with rare genitourinary (GU) tumors that has spread from where it first started (primary site) to other places in the body. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib, nivolumab, and ipilimumab may work better in treating patients with genitourinary tumors that have no treatment options compared to giving cabozantinib, nivolumab, or ipilimumab alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
ALL
18 Years and over
PHASE2
NCT03866382
STU-2019-1012
Inclusion Criteria:
* Metastatic disease defined as new or progressive lesions on cross-sectional imaging or bone scan. Patients must have at least:
* One measurable site of disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
* One bone lesion on bone scan (tec99 or sodium fluoride \[NaF\] PET/CT, CT or MRI) for the bone-only cohort.
* Histologically confirmed diagnosis of one of the following metastatic cohorts:
* Small cell/ neuroendocrine carcinoma of the bladder (Cohort A)- All urothelial carcinomas with any amount of neuroendocrine differentiation (including small cell differentiation) will be included. If the tumor is purely neuroendocrine, metastasis from another site of origin should be clinically excluded
* Adenocarcinoma of the bladder, or urachal adenocarcinoma, or bladder/urethra clear cell adenocarcinoma (Cohort B) - must be pure (per World Health Organization \[WHO\] definition), (i.e. urothelial carcinoma with glandular differentiation is not considered a pure adenocarcinoma
* Squamous cell carcinoma of the bladder (Cohort C) - must be pure (i.e. urothelial carcinoma with squamous differentiation is not considered a pure squamous cell carcinoma)
* Plasmacytoid urothelial carcinoma (Cohort D) - Tumor should show predominantly \> or equal \~ 50% plasmacytoid histology (including all types of discohesive growth, such as tumors with signet-ring and/or rhabdoid features as well)
* Any penile cancer (Cohort E)
* Sarcomatoid renal cell carcinoma (Cohort F) - Tumor should be predominantly sarcomatoid \~ 50% (including rhabdoid differentiation) is also unclassified renal cell carcinomas (RCCs): all (assuming they are high grade with metastasis) malignant angiomyolipomas are allowed
* Other miscellaneous histologic variants of the urothelial carcinoma, such as, but not limited to (Cohort G) : Micropapillary (Tumor should show predominantly \> or equal 50% micropapillary architecture), giant cell, lipid-rich, clear cell and nested variants (Tumor should predominantly \> or equal 50% show these features), large cell neuroendocrine carcinoma, lymphoepithelioma-like carcinoma and mixed patterns will be considered, as well as small cell neuroendocrine prostate cancer (Only treatment-naïve primary small cell of prostate with any amount of small cell component allowed. Post-treatment small cell prostatic carcinomas are not allowed), Malignant testicular Sertoli or Leydig cell tumors, and papillary and chromophobe RCC
* Note: Translocation positive renal cell carcinoma patients are eligible. However, AREN1721 should be considered before this trial
* Sarcomatoid urothelial carcinoma (Cohort H) - Tumor should show predominantly \~ 50% sarcomatoid differentiation
* Renal medullary carcinoma (Cohort I) - Per World Health Organization (WHO) definition, ideally confirmed with immunostains
* Bone-only metastatic GU tumors (non-prostate) (Cohort J) - All genitourinary histologies, except prostate are eligible
* Renal Collecting Duct Carcinoma (Cohort K) - Per WHO definition (medullary involvement, predominant tubular morphology, desmoplastic stromal reaction, high grade cytology, infiltrative growth pattern, and absence of other renal cell carcinoma subtype or urothelial carcinoma)
* Urethra carcinoma (Cohort L) - May be of any histology but if urothelial carcinoma then must be isolated to the urethra and not have metachronous or synchronous urothelial carcinoma of the bladder
* H\&E slides from diagnostic tumor tissue for retrospective central pathology review
* Patients may have received up to 2 systemic anti-cancer treatments or be treatment naive. Patients with small cell carcinoma should have received a platinum-based combination regimen either as neoadjuvant, adjuvant or first-line treatment). Patients in the bone-only cohort may be urothelial carcinoma histology but must receive standard cisplatin-based chemotherapy (if cisplatin-eligible)
* Age \>= 18 years
* Patients must be able to swallow oral formulation of the tablets
* Karnofsky performance status \>= 80%
* Absolute neutrophil count (ANC) \>= 1,000/mcL
* Platelet count \>= 75,000/mcL
* Total bilirubin =\< 1.5 x upper limit of normal (ULN). For subjects with known Gilbert's disease or similar syndrome with slow conjugation of bilirubin, total bilirubin =\< 3.0 mg/dL
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3.0 x institutional upper limit of normal (ULN) (or =\< 5 x ULN for patients with liver metastases or Gilbert's disease)
* Creatinine =\< 1.5 x upper limit of normal (ULN) OR creatinine clearance \>= 40 mL/min/1.73 m\^2 (calculated using the Chronic Kidney Disease Epidemiology \[CKD-EPI\] equation or Cockcroft-Gault formula) for patients with creatinine levels above institutional normal
* Hemoglobin \>= 9 g/dL (transfusion of packed red blood cells \[PRBCs\] allowed)
* Serum albumin \>= 3.2 g/dL
* Lipase and amylase =\< 2.0 x ULN and no radiologic (on baseline anatomical imaging) or clinical evidence of pancreatitis
* Prior treatment with MET or VEGFR inhibitors is allowed. However, prior cabozantinib will not be allowed. Also, patients that have received both prior MET or VEGF and prior PD-1/PD-L1/CTLA-4 (sequentially or in combination) are also not allowed
* No prior treatment with any therapy on the PD-1/PD-L1 axis or anti- CTLA-4/CTLA-4 inhibitors with the exception of patients with "urothelial carcinoma" histology (cohorts D, H, J, L)
* Human immunodeficiency virus (HIV)-positive patients are eligible if on stable dose of highly active antiretroviral therapy (HAART), no clinically significant drug-drug interactions are anticipated with the current HAART regimen, CD4 counts are greater than 350 and viral load is undetectable
* Patients with rheumatoid arthritis and other rheumatologic arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication only and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies etc. are eligible but should be considered for rheumatologic evaluation for the presence of target organ involvement and potential need for systemic treatment
* Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones or medications (e.g. thyroiditis managed with propylthiouracil \[PTU\] or methimazole) including physiologic oral corticosteroids are eligible
* Patients who have evidence of active or acute diverticulitis, intra-abdominal abscess, and gastrointestinal (GI) obstruction, within 12 months are not eligible
* Women of childbearing potential must have a negative pregnancy test =\< 7 days prior to registration
* Women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Post menopause is defined as amenorrhea \>= 12 consecutive months. Note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason
* Pregnant women may not participate in this study because with cabozantinib, nivolumab, and ipilimumab have potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cabozantinib, nivolumab, and ipilimumab, breastfeeding should be discontinued if the mother is treated with these agents
* The patient has received no cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 2 weeks before the first dose of study treatment
* The patient has received no radiation therapy:
* To the lungs and mediastinum or abdomen within 4 weeks before the first dose of study treatment, or has ongoing complications, or is healing from prior radiation therapy
* To brain metastasis within 3 weeks for whole-brain radiotherapy (WBXRT), and 2 weeks for stereotactic body radiation therapy (SBRT) before the first dose of study treatment
* To the abdomen within 4 weeks before the first dose of study treatment, or has ongoing complications, or is healing from prior radiation therapy
* To any other site(s) within 2 weeks before the first dose of study treatment
* The patient has received no radionuclide treatment within 6 weeks of the first dose of study treatment
* The patient has received no prior treatment with a small molecule kinase inhibitor within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment
* The patient has received no prior treatment with hormonal therapy within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment. Subjects receiving gonadotropin-releasing hormone (GnRH) agonists and antagonists are allowed to participate
* The patient has not received any other type of investigational agent within 14 days before the first dose of study treatment
* The patient must have recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =\< grade 1 from toxicity due to all prior therapies except alopecia, neuropathy and other non-clinically significant adverse events (AEs) defined as lab elevation with no associated symptoms or sequelae
* The patient may not have active brain metastases or epidural disease. Patients with brain metastases previously treated with whole brain radiation or radiosurgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible. Neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment. Baseline brain imaging with contrast-enhanced CT or MRI scans for subjects with known brain metastases is required to confirm eligibility
* No concomitant treatment with warfarin. Aspirin (up to 325 mg/day), thrombin or factor Xa inhibitors, low-dose warfarin (=\< 1 mg/day), prophylactic and therapeutic low molecular weight heparin (LMWH) are permitted
* No chronic concomitant treatment with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort) or strong CYP3A4 inhibitors
* Because the lists of these agents are constantly changing, it is important to regularly consult medical reference texts such as the Physicians' Desk Reference may also provide this information. 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
* The patient has not experienced any of the following:
* Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment
* Hemoptysis of \>= 0.5 teaspoon (2.5 mL) of red blood per day within 1 months before the first dose of study treatment
* Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
* The patient has no tumor invading any major blood vessels
* The patient has no evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib. Patients with rectal tumor masses are not eligible
* The patient has no uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
* Cardiovascular disorders including:
* Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening.
* Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) \> 150 mm Hg systolic, or \> 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment
* The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) \> 500 ms within 28 days before randomization. Note: if initial QTcF is found to be \> 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed. If the average of these three consecutive results for QTcF is =\< 500 ms, the subject meets eligibility in this regard
* Any history of congenital long QT syndrome
* Any of the following within 6 months before registration of study treatment:
* Unstable angina pectoris
* Clinically-significant cardiac arrhythmias (patients with atrial fibrillation are eligible)
* Stroke (including transient ischemic attack \[TIA\], or other ischemic event)
* Myocardial infarction
* Cardiomyopathy
* No significant gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:
* Any of the following that have not resolved within 28 days before the first dose of study treatment:
* Active peptic ulcer disease
* Acute diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or malabsorption syndrome
* None of the following within 2 years before the first dose of study treatment:
* Abdominal fistula or genitourinary fistula
* Gastrointestinal perforation
* Bowel obstruction or gastric outlet obstruction
* Intra-abdominal abscess. Note: Complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more than 2 years before the first dose of study treatment
* Disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement are not eligible
* No other clinically significant disorders such as:
* Severe active infection requiring IV systemic treatment within 14 days before the first dose of study treatment
* Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment
* History of organ or allogeneic stem cell transplant
* Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment (for asymptomatic patients with an elevated thyroid-stimulating hormone \[TSH\], thyroid replacement may be initiated if clinically indicated without delaying the start of study treatment)
* No history of major surgery as follows:
* Major surgery within 3 months of the first dose of cabozantinib; however, if there were no wound healing complications, patients with rapidly growing aggressive cancers, may start as soon as 6 weeks if wound has completely healed post-surgery
* Minor surgery within 1 month of the first dose of cabozantinib if there were no wound healing complications or within 3 months of the first dose of cabozantinib if there were wound complications excluding core biopsies and mediport placement
* Complete wound healing from prior surgery must be confirmed before the first dose of cabozantinib irrespective of the time from surgery
* No history of severe hypersensitivity reaction to any monoclonal antibody
* No evidence of active malignancy, requiring systemic treatment within 2 years of registration
* No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib, nivolumab, ipilimumab or other agents used in study
* No positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection. If HBV sAG is positive, subsequent ribonucleic acid (RNA) polymerase chain reaction (PCR) must be negative
* No patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include, but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, DRUG: Cabozantinib S-malate, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography Test, BIOLOGICAL: Ipilimumab, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Nivolumab, PROCEDURE: Positron Emission Tomography
Bladder Adenocarcinoma, Bladder Clear Cell Adenocarcinoma, Bladder Mixed Adenocarcinoma, Bladder Neuroendocrine Carcinoma, Bladder Small Cell Neuroendocrine Carcinoma, Bladder Squamous Cell Carcinoma, Chromophobe Renal Cell Carcinoma, Collecting Duct Carcinoma, Invasive Bladder Giant Cell Urothelial Carcinoma, Invasive Bladder Lymphoepithelioma-Like Carcinoma, Invasive Bladder Nested Urothelial Carcinoma, Invasive Bladder Plasmacytoid Urothelial Carcinoma, Invasive Bladder Sarcomatoid Urothelial Carcinoma, Invasive Bladder Urothelial Carcinoma, Kidney Medullary Carcinoma, Large Cell Neuroendocrine Carcinoma, Malignant Testicular Leydig Cell Tumor, Malignant Testicular Sertoli Cell Tumor, Metastatic Bladder Carcinoma, Metastatic Bladder Clear Cell (Glycogen-Rich) Urothelial Carcinoma, Metastatic Bladder Giant Cell Urothelial Carcinoma, Metastatic Bladder Large Cell Neuroendocrine Carcinoma, Metastatic Bladder Lipid-Rich Urothelial Carcinoma, Metastatic Bladder Micropapillary Urothelial Carcinoma, Metastatic Bladder Plasmacytoid Urothelial Carcinoma, Metastatic Bladder Sarcomatoid Urothelial Carcinoma, Metastatic Bladder Small Cell Neuroendocrine Carcinoma, Metastatic Bladder Squamous Cell Carcinoma, Metastatic Chromophobe Renal Cell Carcinoma, Metastatic Kidney Medullary Carcinoma, Metastatic Malignant Genitourinary System Neoplasm, Metastatic Papillary Renal Cell Carcinoma, Metastatic Penile Carcinoma, Metastatic Prostate Small Cell Neuroendocrine Carcinoma, Metastatic Sarcomatoid Renal Cell Carcinoma, Metastatic Urethral Carcinoma, Papillary Renal Cell Carcinoma, Sarcomatoid Renal Cell Carcinoma, Stage IV Bladder Cancer AJCC v8, Stage IV Penile Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Stage IV Urethral Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8, Urachal Adenocarcinoma, Urethral Clear Cell Adenocarcinoma, Kidney, Other Male Genital, Other Urinary, Urinary Bladder
UT Southwestern