Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Behaviors and Mental Disorders

Nervous System Diseases

Rare Diseases

Carcinoma

Small Cell Lung Carcinoma

Carcinoma, Neuroendocrine

Prostatic Neoplasms

Carcinoma, Small Cell

Aggression

Lung Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

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Aberrant Motor Behavior in Dementia

Behavioral Symptoms

Neuroendocrine Tumors

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Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

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Bronchial Neoplasms

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Lung Diseases

Respiratory Tract Diseases

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Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Carboplatin

Niraparib

Taxane

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

INDUCTION: Patients receive cabazitaxel IV over 60 minutes and carboplatin IV over 60 minutes on day 1. Beginning cycle 2, patients also receive cetrelimab IV over 30-60 minutes on day 1. Treatment repeats for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive niraparib orally PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

INDUCTION: Patients receive cabazitaxel IV over 60 minutes and carboplatin IV over 60 minutes on day 1. Beginning cycle 2, patients also receive cetrelimab IV over 30-60 minutes on day 1. Treatment repeats for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive cetrelimab IV over 30 minutes on day 1 and niraparib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cabazitaxel

Cetrelimab

Ana Aparicio

This phase II trial studies the effect of cabazitaxel, carboplatin, and cetrelimab followed by niraparib with or without cetrelimab in treating patients with aggressive variant prostate cancer that has spread to other places in the body (metastatic). Chemotherapy drugs, such as cabazitaxel and carboplatin, 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. PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as niraparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Immunotherapy with monoclonal antibodies, such as cetrelimab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving niraparib with or without cetrelimab, after treatment with cabazitaxel, carboplatin, and cetrelimab, may help control aggressive variant prostate cancer.

PRIMARY OBJECTIVES:

I. Estimate the progression free survival of men with aggressive variant prostate carcinoma (AVPC) treated with induction cabazitaxel-carboplatin and cetrelimab followed by maintenance niraparib with or without cetrelimab.

II. Evaluate changes in the density and localization of immune markers and cell subsets in AVPC tumors treated with or without cetrelimab added to cabazitaxel-carboplatin induction and niraparib maintenance, and screen for their association with outcomes.

SECONDARY OBJECTIVES:

I. Determine the percentage of patients that are able to complete the 6 cycles of induction chemoimmunotherapy.

II. Estimate the Response Evaluation Criteria in Solid Tumors (RECIST), prostate specific antigen (PSA) and circulating tumor cells (CTC) responses in men with AVPC treated with induction cabazitaxel-carboplatin and cetrelimab followed by maintenance niraparib with or without cetrelimab.

III. Estimate the overall survival of men with AVPC treated with induction cabazitaxel-carboplatin and cetrelimab followed by maintenance niraparib with or without cetrelimab.

IV. Determine the safety and tolerability of each of the regimens. V. Determine the frequency of PD-L1 expression in tumors treated with cabazitaxel-carboplatin induction and niraparib maintenance and its association with outcomes.

VI. Collect and archive solid and liquid tumor samples from study patients for later hypothesis generating associations.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I:

INDUCTION: Patients receive cabazitaxel intravenously (IV) over 60 minutes and carboplatin IV over 60 minutes on day 1. Beginning cycle 2, patients also receive cetrelimab IV over 30-60 minutes on day 1. Treatment repeats for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive niraparib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

GROUP II:

INDUCTION: Patients receive cabazitaxel IV over 60 minutes and carboplatin IV over 60 minutes on day 1. Beginning cycle 2, patients also receive cetrelimab IV over 30-60 minutes on day 1. Treatment repeats for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive cetrelimab IV over 30 minutes on day 1 and niraparib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment patients are followed up for 30 to 90 days (after last dose cetrelimab), and then every 6 months thereafter.

Cabazitaxel, Carboplatin, and Cetrelimab Followed by Niraparib With or Without Cetrelimab for the Treatment of Aggressive Variant Metastatic Prostate Cancer

Randomized Phase II Study of Platinum-Taxane-Cetrelimab Induction Followed by Niraparib Plus or Minus Cetrelimab Maintenance in Men With Aggressive Variant Prostate Cancers

Estimated by the methods of Kaplan and Meier. The 2 randomized treatment arms will be compared by a log rank test.

Defined as the proportion of patients with reduction in tumor burden. Evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Will be reported separately for induction and for each randomized arm.

Defined as the proportion of patients with reduction in tumor burden. Evaluated by prostate specific antigen (PSA) response criteria. PSA will be considered evaluable for assessment of PSA response if \>= 1.0 ng/ml. Will be reported separately for induction and for each randomized arm.

Defined as the proportion of patients with reduction in tumor burden. Will be reported separately for induction and for each randomized arm.

Toxicity will be scored using Common Terminology Criteria for Adverse Events (CTCAE) version 5 for toxicity and adverse event reporting. Descriptive tables will be provided for adverse events by grade and attribution for the cabazitaxel/carboplatin for all patients, and then separately for patients receiving niraparib maintenance vs niraparib + cetrelimab. The numbers of cycles prior to and post randomization will be reported for each arm.

Janssen Pharmaceutica

M.D. Anderson Cancer Center

Carcinoma, Transitional Cell

Carcinoma, Renal Cell

Kidney Neoplasms

Urologic Neoplasms

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Transitional Cell Carcinoma

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antibodies

Antibodies, Monoclonal

Ipilimumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive valemetostat PO QD on days 1-21 and ipilimumab IV over 90 minutes on day 1 of cycles 1 and 3. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Valemetostat

This phase Ib trial studies the side effects and best dose of DS3201 when given together with and ipilimumab for the treatment of patients with prostate, urothelial, or renal cell cancer that has spread to other places in the body (metastatic). DS3201 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as 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 DS3201 and ipilimumab may help to control the disease.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) and confirm the safety and tolerability of valemetostat (DS3201) given in combination with ipilimumab in patients with metastatic aggressive variant prostate cancers (AVPC), urothelial carcinomas (UC) and renal clear cell carcinomas (RCC).

II. To screen for associations between changes in the tumor microenvironment and clinical outcomes.

SECONDARY OBJECTIVES:

I. To assess the immunologic and molecular effects on tissue samples of participants treated with DS3201 in combination with ipilimumab in patients with metastatic AVPC, UC and RCC.

II. To estimate the time to treatment failure (TTF) of patients with metastatic AVPC, UC and RCC treated with DS3201 in combination with ipilimumab.

III. To estimate the overall response rate (ORR) of patients with metastatic AVPC, UC and RCC treated with DS3201 in combination with ipilimumab (in patients with AVPC ORR will be reported separately for prostate specific antigen \[PSA\], circulating tumor cells \[CTC\] and measurable and non-measurable disease by Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1).

OUTLINE: This is a dose-escalation study of valemetostat.

Patients receive valemetostat orally (PO) once daily (QD) on days 1-21 and ipilimumab intravenously (IV) over 90 minutes on day 1 of cycles 1 and 3. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up 30 and 60 days after the last valemetostat dose and/or 100 days after the last ipilimumab dose and then every 6 months thereafter.

DS3201 and Ipilimumab for the Treatment of Metastatic Prostate, Urothelial and Renal Cell Cancers

DS3201 With Ipilimumab in Patients With Metastatic Aggressive Variant Prostate (AVPC), Urothelial (UC), and Renal Cell (RCC) Carcinomas

Adverse events will be graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 and tabulated by grade and ETOX status. All adverse events will be presented descriptively by event, grade, and attribution separately by dose level.

Descriptive statistics including plots, mean, median and standard deviations will be used to summarize data by dose level and patient disease cohort. Tumor immune cell infiltration and peripheral blood immune populations will be described and graphed over time. Differences in either time point compared to baseline will be compared with a t-test or non-parametric alternative. Cox models will be implemented to explore the relationship of treatment combination, tumor immune infiltration/peripheral blood immune subpopulations, and time to treatment failure.

Defined as the time interval between the first day of treatment with DS3201 and treatment failure. Median TTF will be reported with a 95% confidence interval using Kaplan-Meier methods. If the median is not reached, then the TTF estimate will be reported with the standard error at a time close to the median follow-up time. The full TTF experience will be presented with a Kaplan-Meier plot overall and by disease cohort.

In patients with renal cell carcinoma and urothelial carcinoma, ORR is defined as the rate of confirmed complete responses + partial responses as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and as assessed by the investigator. In patients with aggressive variant prostate cancer, ORR will be reported separately for prostate specific antigen (\>= 50% decline from baseline value), CTC (conversion from unfavorable to favorable counts) and measurable and non-measurable disease (per RECIST 1.1) and as assessed by the investigator. ORR will be reported with a 95% Blythe-Still-Casella exact confidence interval.

National Cancer Institute (NCI)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Cabazitaxel, Carboplatin, and Cetrelimab Followed by Niraparib With or Without Cetrelimab for the Treatment of Aggressive Variant Metastatic Prostate Cancer	NCT04592237	Aggressive Vari... Castration-Resi... Metastatic Pros... Metastatic Pros... Metastatic Pros... Stage IV Prosta...	Cabazitaxel Carboplatin Cetrelimab Niraparib	18 Years -	M.D. Anderson Cancer Center
DS3201 and Ipilimumab for the Treatment of Metastatic Prostate, Urothelial and Renal Cell Cancers	NCT04388852	Aggressive Vari... Castration-Resi... Metastatic Clea... Metastatic Mali... Metastatic Pros... Metastatic Urot... Stage IV Prosta... Stage IV Renal ... Stage IVA Prost... Stage IVB Prost...	Ipilimumab Valemetostat	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for aggressive variant prostate carcinoma