Metastatic Castrate Resistant Prostate CancerPhase 2COBRANCT04038502
Carboplatin or Olaparib for BRcA Deficient Prostate Cancer
A Phase 2 study testing Carboplatin and Olaparib in people with Metastatic Castrate Resistant Prostate Cancer and BARD1, BRCA1, BRCA2, BRIP1, CHEK1, FANCL, PALB2, run by VA Office of Research and Development at 18 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Metastatic Castrate Resistant Prostate Cancer, BARD1, BRCA1, BRCA2, BRIP1, CHEK1, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L Mutations
- What is being tested?
- Carboplatin and Olaparib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 18 sitesUnited States
- Study dates
- 1 Oct 2019to 31 Aug 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed study informed consent form (ICF) and HIPAA authorization form
- 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 nanograms per milliliter (ng/ml) for patients on GnRH analogues or antagonists) and at least one of the following:
- Prostate-specific antigen (PSA) level of at least 2 nanograms per milliliter (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)
Show all 17Show fewer
- 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 grams per deciliter (g/dL)
- Absolute neutrophil count (ANC) > 1.5 x 109/liter (L)
- Platelet count > 100 x 109/L
- Total bilirubin < 1.5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT) < 2.5 x institutional upper limit of normal unless liver metastases are present in which case, they must be < 5x ULN
- Patients must have creatinine clearance estimated using the Cockcroft-Gault equation of >51 mL/min: Estimated creatinine clearance =(140-age [years]) x weight (kg)/(serum creatinine (mg/dL) x 72)
Who cannot join
- Currently receiving active therapy for other neoplastic disorder(s)
- Concurrent enrollment in another clinical investigational drug or device study
- Histologic evidence of small cell carcinoma (morphology alone - immunohistochemical evidence of neuroendocrine differentiation without morphologic evidence is not exclusionary)
- 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)
Show all 14Show fewer
- 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
Trial locations and contacts
18 sites in 1 country. Contact the study team or a site near you to ask about taking part.
18 sites in 1 country
United States18 sites, 15 recruiting
- Recruiting
VA Ann Arbor Healthcare System, Ann Arbor, MI
Ann Arbor, Michigan, 48105
Ramnath Nithya, MD, 734-845-5800, Nithya.Ramnath@va.gov
- Recruiting
Rocky Mountain Regional VA Medical Center, Aurora, CO
Aurora, Colorado, 80045
Daniel Bowles, Daniel.bowles@va.gov
- Terminated
Bay Pines VA Healthcare System, Pay Pines, FL
Bay Pines, Florida, 33744-0000
- Recruiting
Boise VA Medical Center, Boise, ID
Boise, Idaho, 83702
Paul Montgomery, MD, Paul.montgomery@va.gov
- Terminated
Jesse Brown VA Medical Center, Chicago, IL
Chicago, Illinois, 60612
- Recruiting
Atlanta VA Medical and Rehab Center, Decatur, GA
Decatur, Georgia, 30033
Wayne Harris, MD, 404-321-6111 ext. 206147
- Recruiting
Durham VA Medical Center, Durham, NC
Durham, North Carolina, 27705-3875
Rhonda L Bitting, MD, 919-286-6180 ext. 5441, rhonda.bitting@va.gov
- Recruiting
Kansas City VA Medical Center, Kansas City, MO
Kansas City, Missouri, 64128
Bruce Montgomery, 206-277-6878
- Recruiting
William S. Middleton Memorial Veterans Hospital, Madison, WI
Madison, Wisconsin, 53705-2254
David Kosoff, david.kosoff@va.gov
- Recruiting
Minneapolis VA Health Care System, Minneapolis, MN
Minneapolis, Minnesota, 55417-2309
Mark Klein, Mark.Klein@va.gov
- Recruiting
Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY
New York, New York, 10010
Daniel Becker, MD, 212-731-6463, daniel.becker2@va.gov
- Recruiting
Orlando VA Medical Center, Orlando, FL
Orlando, Florida, 32827
Priya Gopalan, MD, priya.gopalan@va.gov
- Recruiting
Philadelphia MultiService Center, Philadelphia, PA
Philadelphia, Pennsylvania, 19106
Kyle Robinson, MD, 215-823-5800 ext. 2371, kyle.robinson3@va.gov
- Recruiting
VA Portland Health Care System, Portland, OR
Portland, Oregon, 97239
Julie Graff, MB, 503-220-8262, julie.graff@va.gov
- Recruiting
VA Puget Sound Health Care System Seattle Division, Seattle, WA
Seattle, Washington, 98108-1532
Robert B Montgomery, MD, (206) 277-6878, Robert.Montgomery@va.gov
Robert B. Montgomery, MD
- Terminated
James J. Peters VA Medical Center, Bronx, NY
The Bronx, New York, 10468-3904
- Recruiting
Washington DC VA Medical Center, Washington, DC
Washington D.C., District of Columbia, 20422-0001
Joao Ascensao, MD, 202-745-8134, Joao.Ascensao@va.gov
- Recruiting
VA Greater Los Angeles Healthcare System, West Los Angeles, CA
West Los Angeles, California, 90073
Matthew Rettig, MD, 310-478-3711 ext. 4761, matthew.rettig@va.gov
About this study
Official title: An Open-label, Multicenter Phase II Study to Compare the Efficacy of Carboplatin as First-line Followed by Second-line Olaparib Versus Olaparib as First-line Followed by Second-line Carboplatin in the Treatment of Patients With Castration Resistant Prostate Cancer Containing Homologous Recombination Deficiency
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.
Read the detailed description
Study General Trial Over-view
This study is designed to help better understand treatment options compared to standard therapies for patients who have targeted DNA repair mutations and metastatic castrate resistant prostate cancer (mCRPC).
Cancer therapies are aimed at finding a way to kill the cancer cells while causing minimal damage to normal (non-cancer) cells. This often works because cancers cells grow faster than many normal cells, many treatments are aimed at to take advantage of that difference. One of the ways to do this is to damage the DNA of these more rapidly growing cells. However, if the cells have a way of repairing that damage then therapies may not work as well. Some research shows that when specific changes or mutations occur in the genes involved with repairing DNA damage, resulting cancers have responded well to drugs which damage DNA.
Olaparib is known as a PARP inhibitor and is standard of care therapy for men with BRCA altered mCRPC. Carboplatin is a synthetic antineoplastic agent which has been used in the treatment of solid tumors and BRCA related cancers. When mutations occur in critical DNA-repair genes, research has found that treatment with carboplatin is also effective.
This research is being done to determine the response of mCRPC in patients with DNA repair mutations to treatment with olaparib compared to carboplatin. This study will test whether giving one drug or the other a has a better response.
Patients wishing to participate in this study are screened for safety and health eligibility before enrolling.
This study is enrolling 100 male participants total, from across the VAMC nationally who have the following:
- Metastatic castration-resistant prostate cancer (mCRPC)
- Cancer that has gotten worse, after any number of first-line treatments
- Mutations in DNA-repair genes discovered as part of a patient's routine care.
Once eligibility is determined, enrolled participants are randomized into one of two groups:
- Group A will start with carboplatin (IV) first, given every 21 days, then have the option to switch to the second treatment with olaparib taken daily, (orally) with cycles of every 28 days.
- Group B will start with olaparib first, taken (orally), with 28 day cycles, then have the option to switch to the second treatment with carboplatin (IV) every 21 days.
Both study drugs in this trial are currently FDA approved, and are prescribed at the participating VAMC clinical sites per institutional guidelines. Carboplatin given in IV is also given as prescribed at the participating VAMC, and administered per institutional guidelines.
Participants are monitored for health and body function, cancer progression, toxicity and life quality at every visit during the trial and at an end of treatment visit (28 days after completion of the trial or after withdrawal). For participants who respond well to treatment during the trial, additional treatment cycles may be added and the study can be extended. Participants who experience intolerable toxicity, cancer progression, or whose doctors decide to change treatment, will either be switched to the opposite study drug or withdrawn from the study.
This important trial is designed to compare response rate and duration of response using carboplatin compared to olaparib in patients who have mCRPC which contains DNA repair gene mutations.
- Conditions
- Metastatic Castrate Resistant Prostate Cancer, BARD1, BRCA1, BRCA2, BRIP1, CHEK1, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L Mutations
- Being tested
- Carboplatin, Olaparib
- Keywords
- metastatic prostate cancer
- Medical subject headings
- Fanconi Anemia, Complementation Group D1, Hereditary Sensory and Autonomic Neuropathies, Fanconi Anemia, Complementation Group N, Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarboplatinDrug
Also called Paraplatin
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.
OlaparibDrug
Also called Lynparza
Olaparib is a targeted therapy drug that is used for mCRPC and is approved by the FDA for this use.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Carboplatin; Drug: Olaparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Through duration of the study, up to 100 weeks
Secondary outcomes (5)
Time interval between randomization and second documented disease progression during or after second-line or death (due to any cause)
Progression-free survival combined, a composite endpoint defined as the time interval between randomization and second documented disease progression reported during or after second-line or death due to any cause
Measured: Through duration of the study, up to 100 weeks
PSA measurements/response
To assess PSA response to initial therapy with carboplatin vs. olaparib
Measured: Through duration of the study, up to 100 weeks
PSA measurements/response
To assess PSA response duration to second line therapy with olaparib vs carboplatin
Measured: Through duration of the study, up to 100 weeks
Grade 3 and 4 toxicities in first and second-line setting
To assess Grade 3 and 4 toxicities for each regimen in the first- and second-line setting
Measured: Through duration of the study, up to 100 weeks
To assess cost effectiveness of carboplatin versus olaparib for the treatment of castration-resistant metastatic prostate cancer
To assess cost effectiveness of carboplatin versus olaparib for the treatment of castration-resistant metastatic prostate cancer
Measured: Through duration of the study, up to 100 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2019
- Study start1 Oct 2019
- Primary completion31 Aug 2027 (estimated)
- Study completion31 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Castrate Resistant Prostate CancerStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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).
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Robert B. Montgomery, MD, Principal investigator, VA Puget Sound Health Care System Seattle Division, Seattle, WARyan Burri, MD, Principal investigator, Bay Pines VA Healthcare System, Pay Pines, FLPhoebe Tsao, MD MSc, Principal investigator, VA Ann Arbor Healthcare System, Ann Arbor, MIManeesh Jain, MD, Principal investigator, Washington DC VA Medical Center, Washington, DC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04038502
- Sponsor's protocol ID
- ONCA-009-18F
- Other IDs
- CX-18-006, 19-08, 01783, 01781, CX001963-01
- Acronym
- COBRA
- Status last verified
- Sep 2026
- First submitted
- 26 Jul 2019
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multicenter Phase II Study to Compare the Efficacy of Carboplatin as First-line Followed by Second-line Olaparib Versus Olaparib as First-line Followed by Second-line Carboplatin in the Treatment of Patients With Castration Resistant Prostate Cancer Containing Homologous Recombination Deficiency
- ClinicalTrials.gov ID
- NCT04038502
- Acronym / sponsor ID
- COBRA / ONCA-009-18F
- Conditions
- Metastatic Castrate Resistant Prostate Cancer, BARD1, BRCA1, BRCA2, BRIP1, CHEK1, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L Mutations
- Keywords
- metastatic prostate cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 1 Oct 2019 (actual)
- Primary completion
- 31 Aug 2027 (estimated)
- Study completion
- 31 Aug 2027 (estimated)
- First posted
- 30 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Study General Trial Over-view
This study is designed to help better understand treatment options compared to standard therapies for patients who have targeted DNA repair mutations and metastatic castrate resistant prostate cancer (mCRPC).
Cancer therapies are aimed at finding a way to kill the cancer cells while causing minimal damage to normal (non-cancer) cells. This often works because cancers cells grow faster than many normal cells, many treatments are aimed at to take advantage of that difference. One of the ways to do this is to damage the DNA of these more rapidly growing cells. However, if the cells have a way of repairing that damage then therapies may not work as well. Some research shows that when specific changes or mutations occur in the genes involved with repairing DNA damage, resulting cancers have responded well to drugs which damage DNA.
Olaparib is known as a PARP inhibitor and is standard of care therapy for men with BRCA altered mCRPC. Carboplatin is a synthetic antineoplastic agent which has been used in the treatment of solid tumors and BRCA related cancers. When mutations occur in critical DNA-repair genes, research has found that treatment with carboplatin is also effective.
This research is being done to determine the response of mCRPC in patients with DNA repair mutations to treatment with olaparib compared to carboplatin. This study will test whether giving one drug or the other a has a better response.
Patients wishing to participate in this study are screened for safety and health eligibility before enrolling.
This study is enrolling 100 male participants total, from across the VAMC nationally who have the following:
- Metastatic castration-resistant prostate cancer (mCRPC)
- Cancer that has gotten worse, after any number of first-line treatments
- Mutations in DNA-repair genes discovered as part of a patient's routine care.
Once eligibility is determined, enrolled participants are randomized into one of two groups:
- Group A will start with carboplatin (IV) first, given every 21 days, then have the option to switch to the second treatment with olaparib taken daily, (orally) with cycles of every 28 days.
- Group B will start with olaparib first, taken (orally), with 28 day cycles, then have the option to switch to the second treatment with carboplatin (IV) every 21 days.
Both study drugs in this trial are currently FDA approved, and are prescribed at the participating VAMC clinical sites per institutional guidelines. Carboplatin given in IV is also given as prescribed at the participating VAMC, and administered per institutional guidelines.
Participants are monitored for health and body function, cancer progression, toxicity and life quality at every visit during the trial and at an end of treatment visit (28 days after completion of the trial or after withdrawal). For participants who respond well to treatment during the trial, additional treatment cycles may be added and the study can be extended. Participants who experience intolerable toxicity, cancer progression, or whose doctors decide to change treatment, will either be switched to the opposite study drug or withdrawn from the study.
This important trial is designed to compare response rate and duration of response using carboplatin compared to olaparib in patients who have mCRPC which contains DNA repair gene mutations.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm 1 - Carboplatin to Olaparib | Active comparator | Drug: Carboplatin, Drug: OlaparibParticipants 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. |
| Treatment Arm 2 - Olaparib to Carboplatin | Active comparator | Drug: Carboplatin, Drug: OlaparibParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Signed study informed consent form (ICF) and HIPAA authorization form
- 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 nanograms per milliliter (ng/ml) for patients on GnRH analogues or antagonists) and at least one of the following:
- Prior therapy with abiraterone acetate, enzalutamide, apalutamide, or darolutamide
Key exclusion criteria (14 listed)
- Currently receiving active therapy for other neoplastic disorder(s)
- Concurrent enrollment in another clinical investigational drug or device study
- Histologic evidence of small cell carcinoma (morphology alone - immunohistochemical evidence of neuroendocrine differentiation without morphologic evidence is not exclusionary)
- Prior treatment with platinum, mitoxantrone or PARP inhibitor for castration resistant prostate cancer
- Known parenchymal brain metastasis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarboplatinAlso: ParaplatinChemotherapy 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. | Drug | Treatment Arm 1 - Carboplatin to Olaparib, Treatment Arm 2 - Olaparib to Carboplatin |
| OlaparibAlso: LynparzaOlaparib is a targeted therapy drug that is used for mCRPC and is approved by the FDA for this use. | Drug | Treatment Arm 1 - Carboplatin to Olaparib, Treatment Arm 2 - Olaparib to Carboplatin |
Primary outcome
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
Time frame: Through duration of the study, up to 100 weeks
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
5 secondary outcomes
Time interval between randomization and second documented disease progression during or after second-line or death (due to any cause)
Time frame: Through duration of the study, up to 100 weeks
PSA measurements/response
Time frame: Through duration of the study, up to 100 weeks
PSA measurements/response
Time frame: Through duration of the study, up to 100 weeks
Grade 3 and 4 toxicities in first and second-line setting
Time frame: Through duration of the study, up to 100 weeks
To assess cost effectiveness of carboplatin versus olaparib for the treatment of castration-resistant metastatic prostate cancer
Time frame: Through duration of the study, up to 100 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Robert B. Montgomery, MD principal investigator
VA Puget Sound Health Care System Seattle Division, Seattle, WA
Ryan Burri, MD principal investigator
Bay Pines VA Healthcare System, Pay Pines, FL
Phoebe Tsao, MD MSc principal investigator
VA Ann Arbor Healthcare System, Ann Arbor, MI
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Carboplatin and Olaparib in people with Metastatic Castrate Resistant Prostate Cancer and BARD1, BRCA1, BRCA2, BRIP1, CHEK1, FANCL, PALB2, run by VA Office of Research and Development at 18 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Robert B Montgomery, MD ((206) 277-6878, Robert.Montgomery@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Through duration of the study, up to 100 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2026.