A Study of Rucaparib Verses Physician's Choice of Therapy in Patients With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency

Overview

  • Study type

    Interventional
  • Study phase

    III
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Rochester, Minnesota: 17-003810
    • Scottsdale/Phoenix, Arizona: 17-003810
    • Jacksonville, Florida: 17-003810
    NCT ID: NCT02975934
    Sponsor Protocol Number: CO-338-063

About this study

The purpose of this study is to determine how patients with metastatic castration-resistant prostate cancer, and evidence of a homologous recombination gene deficiency, respond to treatment with rucaparib verses treatment with physician's choice of abiraterone acetate, enzalutamide, or docetaxel.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria:

  • Male ≥ 18 years of age at the time the informed consent form is signed.
  • Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate (pure small-cell histologies or pure high-grade neuroendocrine histologies are excluded; neuroendocrine differentiation is allowed) that is metastatic.
  • Surgically or medically castrated, with serum testosterone levels of ≤ 50 ng/dL (1.73 nM). If currently being treated with luteinizing hormone–releasing hormone (LHRH) analogs (patients who have not undergone an orchiectomy), therapy must be continued throughout the study.
  • Eligible for treatment with physician’s choice of comparator treatment, selected prior to randomization, per the corresponding prescribing information.
  • Evidence of disease progression after treatment with one prior next-generation AR-targeted therapy (abiraterone acetate, enzalutamide, apalutamide, or investigational AR-targeted agent); treatment with the older anti-androgen therapies such as bicalutamide, flutamide, and nilutamide are not counted toward this limit.
  • Disease progression after initiation of most recent therapy is based on any of the following criteria:
    • Rise in PSA: a minimum of two consecutive rising levels, with an interval of ≥ 1 week between each determination. The most recent screening measurement must have been ≥ 2 ng/mL;
    • Transaxial imaging: new or progressive soft tissue masses on CT or MRI scans as defined by modified RECIST Version 1.1;
    • Radionuclide bone scan: at least two new metastatic lesions.
  • All patients must have a deleterious gene mutation in BRCA1/2 or ATM. Mutations may be identified by local testing or through central testing by the sponsor of plasma or tumor tissue.
  • For local test results, the classification of the mutation as deleterious must be documented in the patient’s medical record.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  • Have adequate organ function confirmed by the following clinical laboratory values obtained within 14 days prior to the first dose of study drug:
    • Bone Marrow Function i. ANC ≥ 1.5 × 109/L:
      • Platelets > 100 × 109/L;
      • Hemoglobin ≥ 10 g/dL independent of transfusion within 14 days.
    • Hepatic Function:
      • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × the upper limit of normal (ULN);
      • Bilirubin ≤ 1.5 × ULN (< 2 x ULN if hyperbilirubinemia is due to Gilbert’s syndrome).
    • c. Renal Function:
      • Estimated glomerular filtration rate (GFR) ≥ 45 mL/min using the Cockcroft-Gault formula.
  • Male patients who are committed to undertaking the following measures for the duration of the study and after the last dose of study drug for the time period specified:
    • Use a condom during sex while being treated and for 6 months after the last dose of study drug;
    • Do not make semen donations during treatment and for 6 months after the last dose of rucaparib;
    • Those with female partners of childbearing potential may be enrolled if they are:
      • Documented to be surgically sterile (ie, vasectomy);
      • Committed to practicing true abstinence during treatment and for 6 months after the last dose of study drug; or
      • Committed to using a highly effective method of contraception (refer to Section 6.5) with their partner during treatment and for 6 months following the last dose of study drug.
  • Have a life expectancy of at least 6 months.

Exclusion Criteria:

  • Active second malignancy, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ, or superficial bladder cancer:
    • Patients with a history of malignancy that has been completely treated, and currently with no evidence of that cancer, are permitted to enroll in the study provided all therapy was completed > 6 months prior and/or bone marrow transplant (BMT) > 2 years prior to first dose of rucaparib.
  • Prior treatment with any PARPi.
  • Prior treatment with chemotherapy (eg docetaxel, mitoxantrone, cyclophosphamide, platinum-based agents) for mCRPC. Prior treatment with docetaxel (or other taxane chemotherapy) administered for castration-sensitive disease is permitted .
  • Symptomatic and/or untreated central nervous system (CNS) metastases. Patients with asymptomatic, previously treated CNS metastases are eligible provided they have been clinically stable (not requiring steroids for at least 4 weeks prior to first dose of study drug) and have appropriate scans at screening assessment.
  • Symptomatic or impending spinal cord compression unless appropriately treated, clinically stable, and asymptomatic.
  • 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.
  • Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or history of chronic hepatitis B or C, with the exception of patients with sustained virologic response after completion of treatment for hepatitis C.
  • Received treatment with chemotherapy, antibody therapy, immunotherapy, gene therapy, angiogenesis inhibitors, or experimental drugs within < 14 days prior to first dose of study drug. Treatment with hormonal therapies (with the exception of LHRH analog) must be discontinued at least 7 days prior to the first dose of study drug.
  • Adverse effect of prior therapy not resolved to CTCAE Grade 1 or below with the exception of alopecia. Ongoing Grade 2 non-hematologic toxicity related to most recent treatment regimen may be permitted with prior advanced approval from the sponsor.
  • Initiated low-dose corticosteroid, bisphosphonate, or denosumab therapy or adjusted low-dose corticosteroid, bisphosphonate, or denosumab dose/regimen within < 28 days prior to first dose of study drug. Patients on a stable low-dose corticosteroid, bisphosphonate, or denosumab regimen are eligible and may continue treatment.
  • Non-study related minor surgical procedure within < 5 days, or major surgical procedure within < 21 days, prior to first dose of study drug; in all cases, the patient must be sufficiently recovered and stable before treatment administration.
  • Presence of any other condition that may increase the risk associated with study participation or may interfere with the interpretation of study results, and, in the opinion of the investigator, would make the patient inappropriate for entry into the study.

 

 

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Alan Bryce, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Alan Bryce, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Alan Bryce, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20366159

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