Clinical Trials /

BRcA Deficient Prostate Cancer Treated With Carboplatin or Docetaxel

NCT04038502

Description:

This is an unblinded, randomized clinical study comparing the efficacy of DNA damaging chemotherapy using carboplatin, to standard of care chemotherapy for patients who have metastatic castrate resistant prostate cancer. This trial will use docetaxel or carboplatin as initial chemotherapy with crossover to the alternate or second-line drug after first progression for patients with tumors containing BRCA1, BRCA2 or PALB2 inactivating DNA mutations. Participants are randomized (1:1) and receive either carboplatin (AUC 5) first or docetaxel (75 mg/m2) every 21 days until intolerance, complete response, or progression by Prostate Cancer Working Group 3 (PCWG3) criteria or 10 cycles (whichever is first). 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 or 10 cycles (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 docetaxel. 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.

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: BRcA Deficient Prostate Cancer Treated With Carboplatin or Docetaxel
  • Official Title: Multicenter Phase II Study of First-line Carboplatin Followed by Docetaxel Versus First-line Docetaxel Followed by Carboplatin for Treatment of Castration Resistant Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: ONCA-009-18F
  • SECONDARY ID: CX-18-006
  • SECONDARY ID: 19-08
  • SECONDARY ID: 01783
  • SECONDARY ID: 01781
  • SECONDARY ID: CX001963-01
  • NCT ID: NCT04038502

Conditions

  • Metastatic Castrate Resistant Prostate Cancer
  • BRCA1, BRCA2, PALB2 Genetic Mutations

Interventions

DrugSynonymsArms
CarboplatinParaplatinTreatment Arm 1 - Carboplatin to Docetaxel
DocetaxelDocefrez, TaxotereTreatment Arm 1 - Carboplatin to Docetaxel

Purpose

This is an unblinded, randomized clinical study comparing the efficacy of DNA damaging chemotherapy using carboplatin, to standard of care chemotherapy for patients who have metastatic castrate resistant prostate cancer. This trial will use docetaxel or carboplatin as initial chemotherapy with crossover to the alternate or second-line drug after first progression for patients with tumors containing BRCA1, BRCA2 or PALB2 inactivating DNA mutations. Participants are randomized (1:1) and receive either carboplatin (AUC 5) first or docetaxel (75 mg/m2) every 21 days until intolerance, complete response, or progression by Prostate Cancer Working Group 3 (PCWG3) criteria or 10 cycles (whichever is first). 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 or 10 cycles (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 docetaxel. 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

      BRACeD Study General Trial Over-view

      Research shows that when some changes or mutations occur in the DNA involved with repairing
      genes, the risk of cancer increases. Patients who have certain kinds of mutations in their
      DNA-repair genes have responded well to drugs which damage DNA but are not part of standard
      therapy for prostate cancer, this study is designed to help better understand treatment
      options for these patients.

      Treatment with a drug called docetaxel is one of the standard chemotherapy treatments for men
      with metastatic castration resistant prostate cancer (mCRPC). Carboplatin is a DNA damaging
      chemotherapy treatment which is used for treatment of cancer, but is not commonly used for
      the treatment of prostate cancer. In early studies, the use of carboplatin has shown very
      promising activity in treatment of prostate cancer. This study is being conducted to evaluate
      patient response to treatment with docetaxel compared to carboplatin.

      Patients wishing to participate in this study are screened for safety and health eligibility
      before enrolling.

      This study is enrolling 40 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 first, given every 21 days for up to 10 cycles, then
           have the option to switch to the second treatment with docetaxel every 21 days.

        -  Group B will start with docetaxel first, given every 21 days for up to 10 cycles, then
           have the option to switch to the second treatment with carboplatin every 21 days.

      Both study drugs in this trial are currently FDA approved, and are given intravenously (IV)
      at the participating VAMC clinical sites 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 docetaxel in patients who have mCRPC which contains DNA repair gene
      mutations.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment Arm 1 - Carboplatin to DocetaxelActive ComparatorParticipants 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), docetaxel is administered 75 mg/m2 IV every 21 days thereafter.
  • Carboplatin
  • Docetaxel
Treatment Arm 2 - Docetaxel to CarboplatinActive ComparatorParticipants are administered docetaxel 75 mg/m2 IV first, which is administered Cycle-1, Day-1, and then every 21 days as first line therapy. For second line (crossover), carboplatin is administered AUC 5 IV every 21 days thereafter.
  • Carboplatin
  • Docetaxel

Eligibility Criteria

        Inclusion Criteria:

          -  Signed study informed consent form (ICF)

          -  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 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, and/or enzalutamide

          -  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
             BRCA1, BRCA2, or PALB2 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.

        Exclusion Criteria:

          -  Currently receiving active therapy for other neoplastic disorder(s)

          -  Concurrent enrollment in another clinical investigational drug or device study

          -  Morphologic evidence of neuroendocrine or small cell carcinoma of the prostate

          -  Prior treatment with platinum or docetaxel chemotherapy for CRPC

          -  Parenchymal brain metastasis

          -  Active or symptomatic viral hepatitis or chronic liver disease

          -  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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:Accepts Healthy Volunteers

Primary Outcome Measures

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:10 cycles for each treatment or progression, whichever comes first (cycles are every 21 days)
Safety Issue:
Description: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 carboplatin vs. docetaxel

Secondary Outcome Measures

Measure: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 six years
Safety Issue:
Description: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
Measure:PSA measurements/response
Time Frame:Through duration of the study, up to six years
Safety Issue:
Description:To assess PSA response to initial therapy with carboplatin vs. docetaxel
Measure:PSA measurements/response
Time Frame:Through duration of the study, up to six years
Safety Issue:
Description:To assess PSA response duration to second line therapy with docetaxel vs carboplatin
Measure:Grade 3 and 4 toxicities in first and second-line setting
Time Frame:Through duration of the study, up to six years
Safety Issue:
Description:To assess Grade 3 and 4 toxicities for each regimen in the first- and second-line setting

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:VA Office of Research and Development

Trial Keywords

  • metastatic prostate cancer

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