Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Symptoms and General Pathology

Nutritional and Metabolic Diseases

Carcinoma

Adenocarcinoma

Prostatic Neoplasms

Disease Progression

DNA Repair-Deficiency Disorders

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

Metabolic Diseases

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Carboplatin

Rucaparib

Tubulin Modulators

Antimitotic Agents

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

INDUCTION: Patients receive docetaxel IV and carboplatin IV on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive rucaparib camsylate PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Rucaparib Camsylate

Heather H. Cheng

This phase II trial studies how well docetaxel with carboplatin followed by rucaparib camsylate works in treating patients with metastatic castration resistant prostate cancer (spread outside of prostate and resistant to testosterone suppression) with homologous recombination DNA repair deficiency. Chemotherapy drugs, such as docetaxel and carboplatin, work to stop the growth of cancer cells, by stopping them from dividing or spreading. Rucaparib camsylate may stop the growth of tumor cells with defects in the ability to repair mistakes in DNA by forcing additional errors so that the cancer cells cannot overcome the number of errors and will then die. Giving induction docetaxel and carboplatin followed by maintenance rucaparib camsylate may work better in treating patients with castration resistant prostate cancer.

OUTLINE:

INDUCTION: Patients receive docetaxel intravenously (IV) and carboplatin IV on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive rucaparib camsylate orally (PO) twice daily (BID) 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 periodically.

Docetaxel, Carboplatin, and Rucaparib Camsylate in Treating Patients With Metastatic Castration Resistant Prostate Cancer With Homologous Recombination DNA Repair Deficiency

PLATI-PARP: A Phase 2 Study of Induction Docetaxel and Carboplatin Followed by Maintenance Rucaparib in Treatment of Patients With Metastatic Castration Resistant Prostate Cancer With Homologous Recombination DNA Repair Deficiency

Rate of confirmed PSA decrease from baseline, assessed by a local laboratory (PSA50 and PSA90)

The increase must be confirmed by a second consecutive assessment conducted at least 3 weeks later.

University of Washington

Azacitidine

Decitabine

Antimetabolites

Participants receive decitabine IV over 1 hour on days 1-5 and enzalutamide PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Enzalutamide

Gurkamal Chatta

This phase I/II trial studies the side effects and best dose of decitabine and how well it works when given together with enzalutamide in treating patients with castration resistant prostate cancer that has spread to other places in the body. Androgen can cause the growth of prostate cancer cells. Drugs, such as enzalutamide, may lessen the amount of androgen made by the body. Decitabine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving decitabine and enzalutamide may work better in treating participants with castration resistant prostate cancer.

PRIMARY OBJECTIVES I. To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of decitabine in combination with enzalutamide in patients with refractory metastatic castrate resistant prostate cancer (mCRPC). (Phase 1b) II. To determine the 12-month progression free survival rate of patients with enzalutamide-naive metastatic castrate resistant prostate cancer (mCRPC) treated with decitabine plus enzalutamide. (Phase 2)

SECONDARY OBJECTIVES:

I. To determine the safety and tolerability of decitabine in combination with enzalutamide in patients with refractory metastatic castrate resistant prostate cancer (mCRPC). (Phase 1b) II. To determine the overall response rate, overall survival and prostate specific antigen (PSA) changes in enzalutamide-naive mCRPC patients treated with decitabine plus enzalutamide. (Phase 2) III. To determine the safety and tolerability of decitabine in combination with enzalutamide in the study population. (Phase 2)

EXPLORATORY OBJECTIVES:

I. To determine the relationship between decitabine dose and plasma biomarkers (e.g., levels of HbF, LINE-1 methylation, number of circulating tumor cell's \[CTC?s\] and, NY-ESO expression in CTC?s). (Phase 1b) II. To explore plasma and tumor immune biomarkers associated with efficacy to the study combination. (Phase 2) III. To determine if treatment emergent neuroendocrine transformation is present as a result of the treatment combination of enzalutamide plus decitabine. (Phase 2) IV. Evaluate changes in stem cell reprogramming factors and deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) markers resulting from the treatment combination. (Phase 2)

OUTLINE: This is a phase Ib, dose-escalation study of decitabine followed by a phase II study.

Participants receive decitabine intravenously (IV) over 1 hour on days 1-5 and enzalutamide orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up every 3 months for 24 months.

Enzalutamide and Decitabine in Treating Patients With Metastatic Castration Resistant Prostate Cancer

Phase Ib/II Study of Enzalutamide With Decitabine, a DNA Hypomethylating Agent, in Patients With Metastatic Castrate Resistant Prostate Cancer (mCRPC)

Will calculate the mean and standard deviation for these markers.

Will calculate the mean and standard deviation for these markers. Correlation of gene expression levels will be measured using Pearson or Spearman correlation coefficients. Association of androgen profiles with clinical outcomes will use logistic regression or Cox proportional hazards regression, as appropriate.

Will calculate the mean and standard deviation for these markers. Correlation of gene expression levels will be measured using Pearson or Spearman correlation coefficients.

Peripheral blood mononuclear cells (PBMC) will be assessed using multiparameter flow cytometry for immune subsets including but not necessarily limited to regulatory T cells (Tregs), myeloid-derived suppressor cell (MDSC), effector and exhausted CD4+ or CD8+ T-cells, and CD14+ monocytes. Assessment will include functional markers, i.e. PD-1, PD-L1, Tim-3, and CTLA-4. Will calculate the mean and standard deviation for these markers.

The dose level at which at least 2 out of 6 patients within the same cohort experience dose-limiting toxicity (DLT).

Adverse event (AE) summaries will be organized by body system, frequency of occurrence, intensity (i.e., severity grade), and causality or attribution. Subjects who experience an AE more than once will be counted only once. The occurrence with the maximum severity will be used to calculate intensity. AEs deemed serious and those resulting in treatment withdrawal or death will be summarized separately.

According to prostate specific antigen (PSA) response (longitudinally), Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1, Prostate Cancer Working Group 3 (PCWG3) criteria and, a longitudinal mixed model for repeated measures of tumor burden: follow serial PSAs and follow target lesions on computed tomography scans and bone scans as per PCWG3 criteria.

The Kaplan-Meier product-limit estimator will be used to estimate PFS distributions.

Roswell Park Cancer Institute

Recurrence

Disease Attributes

Fluorides

Protective Agents

Computed Tomography

Fluorine F 18 DCFPyL

Positron Emission Tomography

Andrei Iagaru

This study provides fluorine F 18 DCFPyL positron emission tomography/computed tomography (PET/CT) to participants with prostate cancer that has come back. Diagnostic procedures, such as fluorine F 18 DCFPyL PET/CT, may help find and diagnose prostate cancer and find out how far the disease has spread.

PRIMARY OBJECTIVES:

I. To evaluate fluorine F 18 DCFPyL (18F-DCFPyL) PET/CT for detection of recurrent prostate cancer after initial therapy in patients with elevated prostate-specific antigen (PSA).

OUTLINE:

Participants receive fluorine F 18 DCFPyL intravenously (IV). After 60-120 minutes, participants undergo whole body PET/CT. Immediately after the first scan, participants may undergo a second PET/CT without receiving fluorine F 18 DCFPyL.

After completion of study, participants are followed up at 24-72 hours.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Docetaxel, Carboplatin, and Rucaparib Camsylate in Treating Patients With Metastatic Castration Resistant Prostate Cancer With Homologous Recombination DNA Repair Deficiency	NCT03442556	ATM Gene Mutati... BRCA1 Gene Muta... BRCA2 Gene Muta... Castration Leve... Castration-Resi... Homologous Reco... Prostate Carcin... PSA Level Great... PSA Progression Stage IV Prosta...	Carboplatin Docetaxel Laboratory Biom... Rucaparib Camsy... Rucaparib	18 Years -	University of Washington
Enzalutamide and Decitabine in Treating Patients With Metastatic Castration Resistant Prostate Cancer	NCT03709550	Castration Leve... Castration-Resi... Metastatic Pros... Prostate Carcin... PSA Level Great... PSA Progression Stage IV Prosta... Stage IVA Prost... Stage IVB Prost...	Decitabine Enzalutamide	18 Years -	Roswell Park Cancer Institute
F18 DCFPyL PET/CT in Imaging Participants With Recurrent Prostate Cancer	NCT03501940	Prostate Adenoc... PSA Level Great... PSA Level Great... PSA Progression Recurrent Prost...	Computed Tomogr... Fluorine F 18 D... Laboratory Biom... Positron Emissi...	18 Years -	Stanford University
Enzalutamide and Decitabine in Treating Patients With Metastatic Castration Resistant Prostate Cancer	NCT03709550	Castration Leve... Castration-Resi... Metastatic Pros... Prostate Carcin... PSA Level Great... PSA Progression Stage IV Prosta... Stage IVA Prost... Stage IVB Prost...	Decitabine Enzalutamide	18 Years -	Roswell Park Cancer Institute
F18 DCFPyL PET/CT in Imaging Participants With Recurrent Prostate Cancer	NCT03501940	Prostate Adenoc... PSA Level Great... PSA Level Great... PSA Progression Recurrent Prost...	Computed Tomogr... Fluorine F 18 D... Laboratory Biom... Positron Emissi...	18 Years -	Stanford University
F18 DCFPyL PET/CT in Imaging Participants With Recurrent Prostate Cancer	NCT03501940	Prostate Adenoc... PSA Level Great... PSA Level Great... PSA Progression Recurrent Prost...	Computed Tomogr... Fluorine F 18 D... Laboratory Biom... Positron Emissi...	18 Years -	Stanford University
Enzalutamide and Decitabine in Treating Patients With Metastatic Castration Resistant Prostate Cancer	NCT03709550	Castration Leve... Castration-Resi... Metastatic Pros... Prostate Carcin... PSA Level Great... PSA Progression Stage IV Prosta... Stage IVA Prost... Stage IVB Prost...	Decitabine Enzalutamide	18 Years -	Roswell Park Cancer Institute

Spots Global Cancer Trial Database for psa level greater than or equal to two