search
Back to results

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

Primary Purpose

Metastatic Castration Resistant Prostate Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Rucaparib
Enzalutamide
Abiraterone
Sponsored by
pharmaand GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Castration Resistant Prostate Cancer focused on measuring CRPC, PARP inhibitor, RAMP, homologous recombination, DNA repair, DNA defect, DNA anomaly, mCRPC, enzalutamide, abiraterone, Zytiga, Xtandi, ADT, AR, ARi

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • Piedmont Cancer Institute, P.C.
  • University of Minnesota
  • Urology Associates, P.C.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm A: Oral rucaparib and enzalutamide

Arm B: Oral rucaparib and abiraterone

Arm Description

Outcomes

Primary Outcome Measures

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).
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.

Secondary Outcome Measures

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.

Full Information

First Posted
November 19, 2019
Last Updated
June 27, 2023
Sponsor
pharmaand GmbH
search

1. Study Identification

Unique Protocol Identification Number
NCT04179396
Brief Title
Study of Oral Rucaparib With Other Anticancer Agents in Metastatic Castration Resistant Prostate Cancer Patients (RAMP)
Acronym
RAMP
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
December 5, 2019 (Actual)
Primary Completion Date
November 25, 2021 (Actual)
Study Completion Date
January 18, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
pharmaand GmbH

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A: Oral rucaparib and enzalutamide
Arm Type
Experimental
Arm Title
Arm B: Oral rucaparib and abiraterone
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Rucaparib
Other Intervention Name(s)
Rubraca, CO-338
Intervention Description
Oral rucaparib will be administered twice daily
Intervention Type
Drug
Intervention Name(s)
Enzalutamide
Other Intervention Name(s)
Xtandi
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Abiraterone
Other Intervention Name(s)
Zytiga
Intervention Description
Abiraterone will be administered once daily with prednisone
Primary Outcome Measure Information:
Title
Evaluate the PK of Rucaparib in Combination With Other Anticancer Agents for mCRPC.
Description
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).
Time Frame
1 week rucaparib only run-in and 1 cycle (28 days) of combination treatment
Title
Incidence of Dose-Limiting Toxicities (DLTs) in Participants Taking Rucaparib in Combination With Other Anticancer Agents for mCRPC
Description
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.
Time Frame
First 2 cycles of rucaparib combination treatment (56 days) for Arm A
Secondary Outcome Measure Information:
Title
Preliminary Overall Confirmed Response Rate (ORR) of Rucaparib in Combination With Other Anticancer Agents for mCRPC.
Description
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.
Time Frame
2 years to complete

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Piedmont Cancer Institute, P.C.
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30318
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Urology Associates, P.C.
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37209
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.

Learn more about this trial

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

We'll reach out to this number within 24 hrs