Docetaxel and Carboplatin for Patients With mCRPC and DNA-Repair Deficiencies
Condition: Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer
MeSH terms: Carcinoma; Prostatic Neoplasms; DNA Repair-Deficiency Disorders
Intervention: Carboplatin; Docetaxel
Intervention description: Chemotherapy; Chemotherapy
Intervention MeSH terms: Carboplatin; Docetaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

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. Known prostate cancer

          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, ATM OR one of the following:

               -  Patients with clearly deleterious germline mutations of other genes involved in
                  homologous DNA repair may be included at the investigator's discretion.

               -  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.

               -  Patients with a signature of homologous recombination deficiency in primary or
                  metastatic tissue may be included (VA Puget Sound only).

        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.