Study of Oral Rucaparib With Other Anticancer Agents in Metastatic Castration Resistant Prostate Cancer Patients (RAMP)

Study Overview
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Brief Summary
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Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Oral Rucaparib in Combination with Other Anticancer Agents in Patients with Metastatic Castration Resistant Prostate Cancer

Official Title
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A Phase 1b, Open-label, Parallel Arm Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Oral Rucaparib in Combination With Other Anticancer Agents in Patients With Metastatic Castration Resistant Prostate Cancer

Conditions
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Metastatic Castration Resistant Prostate Cancer

Intervention / Treatment
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* Drug: Rucaparib
* Drug: Enzalutamide
* Drug: Abiraterone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have signed an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent form prior to any study-specific evaluation Be ≥18 yrs of age at the time the informed consent form is signed Be either AR-directed therapy-naive or have received 1-2 lines of AR-directed therapy in the castration-resistant setting. Adequate organ function ECOG 0 or 1 Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate that is metastatic Be surgically or medically castrated, with serum testosterone levels of ≤ 50 ng/dL (1.73 nM) Have disease progression after initiation of most recent therapy Exclusion Criteria: Active second malignancy, with the exception of curatively treated non melanoma skin cancer, carcinoma in situ, or superficial bladder cancer Have received greater than 2 previous lines of chemotherapy for mCRPC Prior treatment with any PARP inhibitor Symptomatic and/or untreated central nervous system metastases Pre-existing duodenal stent and/or any gastrointestinal disorder or defect that would, in the opinion of the investigator, interfere with absorption of study drug Spinal cord compression, symptomatic and/or untreated central nervous system (CNS) metastases or leptomeningeal disease. Patients with asymptomatic previously treated CNS metastases are eligible provided they have been clinically stable for at least 4 weeks Any clinically significant cardiovascular disease Taking any concomitant medications or herbs that could interfere or interact with the study drug

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Oral rucaparib and enzalutamide<br> | Drug: Rucaparib<br>* Oral rucaparib will be administered twice daily<br>* Other names: CO-338;Drug: Enzalutamide<br>* Enzalutamide will be administered once daily. Enrollment into Arm A will be prioritized over Arm B until the objectives for Arm A have been achieved.<br>* Other names: Xtandi;|
| Experimental: Arm B: Oral rucaparib and abiraterone<br> | Drug: Rucaparib<br>* Oral rucaparib will be administered twice daily<br>* Other names: CO-338;Drug: Abiraterone<br>* Abiraterone will be administered once daily with prednisone<br>* Other names: Zytiga;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the PK of Rucaparib in Combination With Other Anticancer Agents for mCRPC. | Cmin of rucaparib and its metabolite. Rucaparib only run-in Cmin includes run-in D6, D7 and Cycle 1 D1. All of these samples were collected following rucaparib monotherapy. Rucaparib and other anticancer agent Combination Cmin includes Cycle 1 (D8, D15, and D22). | 1 week rucaparib only run-in and 1 cycle (28 days) of combination treatment | 
| Incidence of Dose-Limiting Toxicities (DLTs) in Participants Taking Rucaparib in Combination With Other Anticancer Agents for mCRPC | A DLT is defined according to criteria specified in the protocol and assessed by the investigator, based on toxicity grade (according to the NCI CTCAE v5.0), clinical significance, and possible relationship to the study drug combination. The toxicity cannot be a recognized adverse effect of enzalutamide, abiraterone or prednisone/prednisolone and/or attributable to mCRPC or mCRPC-related processes under investigation. | First 2 cycles of rucaparib combination treatment (56 days) for Arm A | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preliminary Overall Confirmed Response Rate (ORR) of Rucaparib in Combination With Other Anticancer Agents for mCRPC. | The ORR is defined as the proportion of patients with a documented and confirmed best overall response of complete response (CR) or partial response (PR) per mRECIST v1.1 as assessed by the investigator using local standardized radiological methods e.g. CT, MRI, etc. A complete response (CR) is defined as complete disappearance of all target and non-target lesions together with normalization of tumor biomarkers. A partial response (PR) represents at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum LD with non-progression of non-target lesions and no new lesions. Overall Response (OR) = CR + PR. A confirmed CR or PR is a response that is maintained and documented on a subsequent tumor assessment at least 4 weeks after initial response. PSA response per PCWG3 criteria is a confirmed PSA response (≥ 50% decrease from baseline) as reflected by local laboratory measurements. | 2 years to complete | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CRPC, PARP inhibitor, RAMP, homologous recombination, DNA repair, DNA defect, DNA anomaly, mCRPC, enzalutamide, abiraterone, Zytiga, Xtandi, ADT, AR, ARi