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

Phase 1

Completed

• Conditions: Metastatic Castration Resistant Prostate Cancer
• Interventions: Drug: Rucaparib; Drug: Abiraterone; Drug: Enzalutamide

• Registration Number: NCT04179396
• Lead Sponsor: pharmaand GmbH

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-11-19
• Study First Submitted QC: 2019-11-25
• Study First Posted: 2019-11-27
• Study Start: 2019-12-05
• Primary Completion: 2021-11-25
• Study Completion: 2023-01-18
• Results First Submitted: 2023-02-06
• Status Verified: 2023-06
• Results First Submitted QC: 2023-06-26
• Last Update Submitted: 2023-06-27
• Results First Posted: 2023-06-28
• Last Update Posted: 2023-06-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 8

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B: Oral rucaparib and abiraterone	Rucaparib	-
Arm A: Oral rucaparib and enzalutamide	Rucaparib	-
Arm B: Oral rucaparib and abiraterone	Abiraterone	-
Arm A: Oral rucaparib and enzalutamide	Enzalutamide	-

Primary Outcome Measures

Name	Time	Method
Evaluate the PK of Rucaparib in Combination With Other Anticancer Agents for mCRPC.	1 week rucaparib only run-in and 1 cycle (28 days) of combination treatment	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).
Incidence of Dose-Limiting Toxicities (DLTs) in Participants Taking Rucaparib in Combination With Other Anticancer Agents for mCRPC	First 2 cycles of rucaparib combination treatment (56 days) for Arm A	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.

Secondary Outcome Measures

Name	Time	Method
Preliminary Overall Confirmed Response Rate (ORR) of Rucaparib in Combination With Other Anticancer Agents for mCRPC.	2 years to complete	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.

Trial Locations

Locations (3)

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

Urology Associates, P.C.; 🇺🇸 Nashville, Tennessee, United States

Piedmont Cancer Institute, P.C.; 🇺🇸 Atlanta, Georgia, United States