Clinical Trials /

Docetaxel and Carboplatin for Patients With mCRPC and DNA-Repair Deficiencies

NCT02985021

Description:

In this study, patients who have metastatic prostate cancer that does not respond to hormone treatment and who have mutations in certain cancer-related genes will be treated with docetaxel and carboplatin chemotherapy.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Docetaxel and Carboplatin for Patients With mCRPC and DNA-Repair Deficiencies
  • Official Title: A Phase 2 Study of Docetaxel and Carboplatin for Treatment of Patients With Metastatic, Castration Resistant Prostate Cancer and Germline or Somatic DNA Repair Deficiency

Clinical Trial IDs

  • ORG STUDY ID: PugetSoundVA
  • NCT ID: NCT02985021

Conditions

  • Hormone-Resistant Prostate Cancer
  • Metastatic Prostate Carcinoma
  • Recurrent Prostate Carcinoma
  • Stage IV Prostate Cancer

Interventions

DrugSynonymsArms
CarboplatinParaplatinTreatment (docetaxel, carboplatin)
DocetaxelTaxotereTreatment (docetaxel, carboplatin)

Purpose

In this study, patients who have metastatic prostate cancer that does not respond to hormone treatment and who have mutations in certain cancer-related genes will be treated with docetaxel and carboplatin chemotherapy.

Detailed Description

      This is a phase 2 study of the combination of docetaxel and carboplatin in patients with
      germline inactivation of genes in the homologous recombination pathway, including BRCA1,
      BRCA2, and ATM.

      PRIMARY OBJECTIVE To assess rate of 50% Prostate Specific Androgen (PSA) decline to docetaxel
      and carboplatin

      EXPLORATORY OBJECTIVES To assess PSA response duration to docetaxel and carboplatin To assess
      response of measurable disease To assess time to progression of bone lesions or measurable
      disease (RECIST) To assess response to docetaxel and carboplatin in patients with germline
      alterations or somatic alterations of DNA repair pathway genes (BRCA1, BRCA2, ATM)
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (docetaxel, carboplatin)ExperimentalDocetaxel 60 mg/m2 will be administered on Day 1 of each 21-day cycle. Carboplatin Area Under the Curve (AUC) 5 will be administered on Day 1 of each 21-day cycle. Docetaxel and carboplatin should be administered over 30 minutes. Treatment will be repeated until disease progression or unacceptable toxicity.
  • Carboplatin
  • Docetaxel

Eligibility Criteria

        Inclusion Criteria

        Patients meeting the following inclusion criteria will be eligible to participate in this
        study:

          1. Signed informed consent form (ICF) providing agreement to adhere to the dosing
             schedule, report for all trial visits and authorization, use and release of health and
             research trial information.

          2. Age > 18 years

          3. Histologically or cytologically confirmed adenocarcinoma of the prostate

          4. 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.

          5. Castration resistant prostate cancer as defined by serum testosterone < 50ng/ml 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 (Response Evaluation Criteria in
                  Solid Tumors).

               -  Progression of metastatic bone disease on bone scan with > 2 new lesions.

          6. Prior therapy with abiraterone acetate, enzalutamide, or docetaxel. There is no limit
             to the number of prior treatment regimens.

          7. Presence of metastatic disease on scans.

          8. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.

          9. Life expectancy >12 weeks.

         10. No prior malignancy is allowed except:

               -  Adequately treated basal cell or squamous cell skin cancer or

               -  In situ carcinoma of any site or

               -  Other adequately treated malignancy for which the patient has been disease-free
                  for at least one year (any prior chemotherapy is allowed).

         11. Patients must have adequate organ and marrow function as defined below obtained within
             14 days prior to start of therapy:

               1. Absolute neutrophil count >1.5 x 109 cells/L

               2. Hgb > 9.0 g/dL

               3. Platelets >100,000 x 109/L

               4. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total
                  bilirubin levels < 1.5 x Upper Limit of Normal (ULN)

         12. Presence of germline inactivation of BRCA1, BRCA2, or ATM (see section 1.1).

         13. Patients with clearly deleterious germline mutations of other genes involved in
             homologous DNA repair may be included at the investigator's discretion.

         14. Patients with homozygous inactivation of genes involved in homologous recombination
             from primary or metastatic tumor as assessed by a Clinical Laboratory Improvement
             Amendments (CLIA) level assay for DNA sequencing may be included.

        Exclusion Criteria

        Patients who meet any of the following criteria will be excluded from the study:

          1. Currently receiving active therapy for other neoplastic disorders.

          2. Histologic evidence of small cell carcinoma (morphology alone - immunohistochemical
             evidence of neuroendocrine differentiation without morphologic evidence is not
             exclusionary).

          3. Prior treatment with platinum-based chemotherapy for prostate cancer.

          4. Known parenchymal brain metastasis.

          5. Active or symptomatic viral hepatitis or chronic liver disease.

          6. 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, if done.

          7. Treatment with an investigational therapeutic within 30 days of Cycle 1.

          8. Patients with dementia/psychiatric illness/social situations limiting compliance with
             study requirements or understanding and/or giving of informed consent are not eligible

          9. Any medical conditions, which, in the opinion of the investigators, would jeopardize
             either the patient or the integrity of the data obtained are not eligible.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of patients achieving >= 50% reduction in PSA according to Prostate Cancer Working Group 3 (PCWG3) criteria
Time Frame:After 10 cycles (210 days), or more per Investigator discretion, or until disease progression or unacceptable toxicity.
Safety Issue:
Description:

Secondary Outcome Measures

Measure:PSA response duration to docetaxel and carboplatin
Time Frame:After 10 cycles (210 days), or more per Investigator discretion, or until disease progression or unacceptable toxicity.
Safety Issue:
Description:
Measure:Response of measurable disease
Time Frame:After 10 cycles (210 days), or more per Investigator discretion, or until disease progression or unacceptable toxicity.
Safety Issue:
Description:
Measure:Time to progression of bone lesions or measurable disease
Time Frame:After 10 cycles (210 days), or more per Investigator discretion, or until disease progression or unacceptable toxicity.
Safety Issue:
Description:
Measure:Proportion of patients responding to docetaxel and carboplatin who have germline alterations or somatic alterations of DNA repair pathway genes (BRCA1, BRCA2, ATM).
Time Frame:After 10 cycles (210 days), or more per Investigator discretion, or until disease progression or unacceptable toxicity.
Safety Issue:
Description:
Measure:Correlation between the presence of DNA repair pathway mutations and copy number alterations in cell free DNA
Time Frame:After 10 cycles (210 days), or more per Investigator discretion, or until disease progression or unacceptable toxicity.
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Seattle Institute for Biomedical and Clinical Research

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