Carboplatin or Olaparib for BRcA Deficient Prostate Cancer

NCT04038502 | Recruiting Phase 2 DMC FDA Drug

• 6 other identifiers: ONCA-009-18FCX-18-00619-080178301781CX001963-01
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 18

Brief Summary

This is an unblinded, randomized clinical study comparing the efficacy of DNA damaging chemotherapy using carboplatin, to standard of care therapy for patients who have metastatic castrate resistant prostate cancer. This trial will use olaparib or carboplatin as initial therapy with crossover to the alternate or second-line drug after first progression for patients with tumors containing BARD1, BRCA1, BRCA2, BRIP1, CHEK1, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L inactivating mutations. Participants are randomized (1:1) and receive either carboplatin (AUC 5, IV) every 21 days, first or olaparib taken orally (300 mg), twice daily in 28 day cycles, until intolerance, complete response, or progression by Prostate Cancer Working Group 3 (PCWG3) criteria. Participants then crossover from the first-line therapy to the second-line therapy with the opposite study medication and receive treatment to intolerance or progression (whichever is first). Enrolled participants will be allowed to crossover to second line therapy if they continue to meet initial eligibility criteria, and at least three weeks have elapsed since last administration of either carboplatin or olaparib. Throughout the study, safety and tolerability will be assessed. Progression will be evaluated with bone scan, CT of the abdomen/pelvis, or MRI and PSA as per PCWG3 criteria.

Conditions

Metastatic Castrate Resistant Prostate Cancer; BARD1, BRCA1, BRCA2, BRIP1, CHEK1, FANCL, PALB2; RAD51B, RAD51C, RAD51D, or RAD54L Mutations

Keywords

metastatic prostate cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS-1L) defined as the time interval between randomization and first documented disease progression or death due to any cause reported during, or after, first-line treatment.

  Progression free survival (PFS) by bone scan or measurable disease, Response Evaluation Criteria in Solid Tumors (RECIST 1.1) to initial therapy (PFS-1L) with either study drug.

  Through duration of the study, up to six years

Secondary Outcomes (4)

• time interval between randomization and second documented disease progression during or after second-line or death (due to any cause)

  Through duration of the study, up to six years

• PSA measurements/response

  Through duration of the study, up to six years

• PSA measurements/response

  Through duration of the study, up to six years

• Grade 3 and 4 toxicities in first and second-line setting

  Through duration of the study, up to six years

Other Outcomes (3)

• Exploratory Objective - PFS

  Through duration of the study, up to six years

• Exploratory Objective - objective response rate

  Through duration of the study, up to six years

• Exploratory Objective- objective duration of response

  Through duration of the study, up to six years

Study Arms (2)

Treatment Arm 1 - Carboplatin to Olaparib

ACTIVE COMPARATOR

Participants are administered carboplatin AUC 5 IV first, which is administered Cycle-1, Day-1, and then every 21 days as first line therapy. For second line (crossover), olaparib is prescribed and taken orally at home, twice daily, 300 mg in 28 day cycles.

Drug: Carboplatin; Drug: Olaparib

Treatment Arm 2 - Olaparib to Carboplatin

ACTIVE COMPARATOR

Participants are prescribed olaparib which is taken orally at home, twice daily, 300 mg in 28 day cycles, as first line therapy. For second line (crossover), carboplatin is administered AUC 5 IV every 21 days thereafter.

Drug: Carboplatin; Drug: Olaparib

Interventions

Carboplatin DRUG

Chemotherapy FDA approved drug used to treat: ovarian, lung, head and neck cancers. It is sometimes used in combination with other medications or off-label use to treat other metastatic cancers.

Also known as: Paraplatin

Treatment Arm 1 - Carboplatin to Olaparib; Treatment Arm 2 - Olaparib to Carboplatin

Olaparib DRUG

Olaparib is a targeted therapy drug that is used for mCRPC and is approved by the FDA for this use.

Also known as: Lynparza

Treatment Arm 1 - Carboplatin to Olaparib; Treatment Arm 2 - Olaparib to Carboplatin

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Biologically sexed males with metastatic prostate cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed study informed consent form (ICF) and HIPAA authorization form
• Male age \> 18 years
• Diagnosis of prostate cancer (pure small-cell histology or pure high-grade neuroendocrine histology are excluded; neuroendocrine differentiation is allowed)
• Ongoing gonadal androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) analogues, antagonists or orchiectomy. Patients who have not had an orchiectomy must be maintained on effective GnRH analogue/antagonist therapy
• mCRPC as defined by serum testosterone \< 50 ng/ml (for patients on GnRH analogues or antagonists) and at least one of the following:
• PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart
• Evaluable disease progression by modified RECIST 1.1 (Response Evaluation Criteria in Solid Tumors)
• Progression of metastatic bone disease on bone scan, CT or MRI with \> 2 new lesions
• Prior therapy with abiraterone acetate, enzalutamide, apalutamide, or darolutamide
• Eastern Cooperative Oncology Group (ECOG) Performance Status of \< 2 (see Appendix 3, ECOG Grading Scale)
• Results of previous standard DNA testing, or previous research testing, which confirms RAD51B, RAD51C, RAD51D, or RAD54L mutations (see Introduction, Section 2 for study design and previous research on targeted therapy) from primary, metastatic tumor or circulating tumor DNA, or pathogenic/likely pathogenic germline variant as assessed by a CLIA certified laboratory level assay for DNA sequencing.
• Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
• Hemoglobin \> 10.0 g/dL
• Absolute neutrophil count (ANC) \> 1.5 x 109/L
• Platelet count \> 100 x 109/L

You may not qualify if:

• Currently receiving active therapy for other neoplastic disorder(s)
• Concurrent enrollment in another clinical investigational drug or device study
• Prior treatment with platinum, mitoxantrone or PARP inhibitor for castration resistant prostate cancer
• Known parenchymal brain metastasis
• Active or symptomatic viral hepatitis or chronic liver disease AST or ALT \> 2.5 x ULN or total bilirubin \> ULN (unless Gilbert's syndrome is the etiology of hyperbilirubinemia)
• Subjects with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML
• Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks
• Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for phenobarbital and 3 weeks for other agents
• Subjects unable to swallow orally administered medication and subjects with gastrointestinal disorders likely to interfere with absorption of the study medication
• Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of \< 35 % at baseline
• Treatment with an investigational therapeutic within 30 days of Cycle-1
• Presence of dementia, psychiatric illness, and/or social situations limiting compliance with study requirements or understanding HIPAA authorization and/or giving of informed consent
• Any condition(s), medical or otherwise, which, in the opinion of the Investigators, would jeopardize either the patient or the integrity of the data obtained.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (18)

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

West Los Angeles, California, 90073, United States

RECRUITING

Rocky Mountain Regional VA Medical Center, Aurora, CO

Aurora, Colorado, 80045, United States

RECRUITING

Washington DC VA Medical Center, Washington, DC

Washington D.C., District of Columbia, 20422-0001, United States

RECRUITING

Bay Pines VA Healthcare System, Pay Pines, FL

Bay Pines, Florida, 33744-0000, United States

TERMINATED

Orlando VA Medical Center, Orlando, FL

Orlando, Florida, 32827, United States

RECRUITING

Atlanta VA Medical and Rehab Center, Decatur, GA

Decatur, Georgia, 30033, United States

RECRUITING

Boise VA Medical Center, Boise, ID

Boise, Idaho, 83702, United States

RECRUITING

Jesse Brown VA Medical Center, Chicago, IL

Chicago, Illinois, 60612, United States

TERMINATED

VA Ann Arbor Healthcare System, Ann Arbor, MI

Ann Arbor, Michigan, 48105, United States

RECRUITING

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota, 55417-2309, United States

RECRUITING

Kansas City VA Medical Center, Kansas City, MO

Kansas City, Missouri, 64128, United States

RECRUITING

Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY

New York, New York, 10010, United States

RECRUITING

James J. Peters VA Medical Center, Bronx, NY

The Bronx, New York, 10468-3904, United States

TERMINATED

Durham VA Medical Center, Durham, NC

Durham, North Carolina, 27705-3875, United States

RECRUITING

VA Portland Health Care System, Portland, OR

Portland, Oregon, 97239, United States

RECRUITING

Philadelphia MultiService Center, Philadelphia, PA

Philadelphia, Pennsylvania, 19106, United States

RECRUITING

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Seattle, Washington, 98108-1532, United States

RECRUITING

William S. Middleton Memorial Veterans Hospital, Madison, WI

Madison, Wisconsin, 53705-2254, United States

RECRUITING

MeSH Terms

Conditions

Fanconi Anemia, Complementation Group D1; Hereditary Sensory and Autonomic Neuropathies; Fanconi Anemia, Complementation Group N; Prostatic Neoplasms

Interventions

Carboplatin; olaparib

Condition Hierarchy (Ancestors)

Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• Robert B. Montgomery, MD

  VA Puget Sound Health Care System Seattle Division, Seattle, WA

  PRINCIPAL INVESTIGATOR

• Ryan Burri, MD

  Bay Pines VA Healthcare System, Pay Pines, FL

  PRINCIPAL INVESTIGATOR

• Phoebe Tsao, MD MSc

  VA Ann Arbor Healthcare System, Ann Arbor, MI

  PRINCIPAL INVESTIGATOR

• Maneesh Jain, MD

  Washington DC VA Medical Center, Washington, DC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Robert B Montgomery, MD

CONTACT

(206) 277-6878; rbmontgo@uw.edu

Makayla L DeJong, BA

CONTACT

(206) 277-4527; Makayla.Dejong@va.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Unblinded, randomized (1:1) clinical study with study-drug treatment in metastatic castrate resistant prostate cancer in patients who have inactivation of the homologous DNA repair pathway, including BARD1, BRCA1, BRCA2, BRIP1, CHEK1, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L with cross-over to opposite study drug after progression or intolerance (whichever comes first).

Study Record Dates

• First Submitted: July 26, 2019
• First Posted: July 30, 2019
• Study Start: October 1, 2019
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: August 20, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (18)