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

NCT04179396 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: CO-338-107
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 3

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

Conditions

Metastatic Castration Resistant Prostate Cancer

Keywords

CRPC; PARP inhibitor; RAMP; homologous recombination; DNA repair; DNA defect; DNA anomaly; mCRPC; enzalutamide; abiraterone; Zytiga; Xtandi; ADT; AR; ARi

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Preliminary Overall Confirmed Response Rate (ORR) of Rucaparib in Combination With Other Anticancer Agents for mCRPC.

  2 years to complete

Study Arms (2)

Arm A: Oral rucaparib and enzalutamide

EXPERIMENTAL

Drug: Rucaparib; Drug: Enzalutamide

Arm B: Oral rucaparib and abiraterone

EXPERIMENTAL

Drug: Rucaparib; Drug: Abiraterone

Interventions

Rucaparib DRUG

Oral rucaparib will be administered twice daily

Also known as: Rubraca, CO-338

Arm A: Oral rucaparib and enzalutamide; Arm B: Oral rucaparib and abiraterone

Enzalutamide DRUG

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.

Also known as: Xtandi

Arm A: Oral rucaparib and enzalutamide

Abiraterone DRUG

Abiraterone will be administered once daily with prednisone

Also known as: Zytiga

Arm B: Oral rucaparib and abiraterone

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• pharmaand GmbH: lead

Study Sites (3)

Piedmont Cancer Institute, P.C.

Atlanta, Georgia, 30318, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Urology Associates, P.C.

Nashville, Tennessee, 37209, United States

Location

MeSH Terms

Interventions

rucaparib; enzalutamide; abiraterone; Abiraterone Acetate

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

Enrollment in the trial was terminated early however sufficient PK and safety data were collected to complete the key objective of elucidating the potential for drug-drug interaction by evaluating PK as well as safety and tolerability of the rucaparib/enzalutamide combination.

Results Point of Contact

• Title: Medical Information Department
• Organization: Clovis Oncology, Inc.

medinfo@clovisoncology.com

+1 415 409 7220

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2019
• First Posted: November 27, 2019
• Study Start: December 5, 2019
• Primary Completion: November 25, 2021
• Study Completion: January 18, 2023
• Last Updated: June 29, 2023
• Results First Posted: June 28, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• 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.

Locations

US (3)