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

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

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

Study Overview

• Status: Completed
• Conditions: Metastatic Castration Resistant Prostate Cancer
• Intervention / Treatment: Drug: Rucaparib; Drug: Enzalutamide; Drug: Abiraterone

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Piedmont Cancer Institute, P.C.
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Tennessee
    • Nashville, Tennessee, United States, 37209
      • Urology Associates, P.C.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Oral rucaparib and enzalutamide	Drug: Rucaparib; Oral rucaparib will be administered twice daily; Other Names: Rubraca; CO-338; Drug: Enzalutamide; 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.; Other Names: Xtandi
Experimental: Arm B: Oral rucaparib and abiraterone	Drug: Rucaparib; Oral rucaparib will be administered twice daily; Other Names: Rubraca; CO-338; Drug: Abiraterone; Abiraterone will be administered once daily with prednisone; Other Names: Zytiga

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: zr Pharma & GmbH

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2019
• Primary Completion (Actual): November 25, 2021
• Study Completion (Actual): January 18, 2023

Study Registration Dates

• First Submitted: November 19, 2019
• First Submitted That Met QC Criteria: November 25, 2019
• First Posted (Actual): November 27, 2019

Study Record Updates

• Last Update Posted (Actual): June 29, 2023
• Last Update Submitted That Met QC Criteria: June 27, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: PARP inhibitor; Xtandi; enzalutamide; mCRPC; abiraterone; ADT; CRPC; Zytiga; RAMP; homologous recombination; DNA defect; DNA repair; DNA anomaly; AR; ARi
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Rucaparib
• Other Study ID Numbers: CO-338-107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

De-identified datasets for study results will be made available to qualified researchers in compliance with applicable privacy laws and data protection regulations.

Data will be provided by Clovis Oncology.

• IPD Sharing Time Frame: Data will be made available to qualified researchers after the primary, secondary, and/or exploratory outcomes of the study are reported or published and for 1 year thereafter.
• IPD Sharing Access Criteria: Requests for de-identified datasets will be made available to qualified researchers following submission of a methodologically sound proposal to medinfo@clovisoncology.com.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No