Clinical Trials /

Docetaxel and Carboplatin in Treating Patients With Metastatic, Castration Resistant Prostate Cancer Containing Inactivated Genes in the BRCA 1/2 Pathway

NCT02598895

Description:

This pilot clinical trial studies docetaxel and carboplatin in treating patients with castration resistant prostate cancer that has spread from the primary site (place where it started) to other places in the body (metastatic) and contains inactivated genes in the BRCA 1/2 pathway. Drugs used in chemotherapy, such as docetaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Docetaxel and Carboplatin in Treating Patients With Metastatic, Castration Resistant Prostate Cancer Containing Inactivated Genes in the BRCA 1/2 Pathway
  • Official Title: A Pilot Study of Docetaxel and Carboplatin for Treatment of Patients With Metastatic, Castration Resistant Prostate Cancer Containing Biallelic Inactivation of Genes in the BRCA1/2 Pathway

Clinical Trial IDs

  • ORG STUDY ID: 9381
  • SECONDARY ID: NCI-2015-01694
  • SECONDARY ID: 9381
  • SECONDARY ID: P30CA015704
  • SECONDARY ID: P50CA097186
  • NCT ID: NCT02598895

Conditions

  • Castration Levels of Testosterone
  • Castration-Resistant Prostate Carcinoma
  • Metastatic Prostate Carcinoma
  • Prostate Carcinoma Metastatic in the Bone
  • PSA Progression
  • Stage IV Prostate Cancer

Interventions

DrugSynonymsArms
CarboplatinBlastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, RibocarboTreatment (docetaxel, carboplatin)
DocetaxelDocecad, RP56976, Taxotere, Taxotere Injection ConcentrateTreatment (docetaxel, carboplatin)

Purpose

This pilot clinical trial studies docetaxel and carboplatin in treating patients with castration resistant prostate cancer that has spread from the primary site (place where it started) to other places in the body (metastatic) and contains inactivated genes in the BRCA 1/2 pathway. Drugs used in chemotherapy, such as docetaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess rate of 50% prostate-specific antigen (PSA) decline to docetaxel and
      carboplatin.

      SECONDARY OBJECTIVES:

      I. To assess PSA response duration to docetaxel and carboplatin. (Phase 2)

      II. To assess response of measurable disease. (Phase 2)

      III. To assess time to progression of bone lesions or measurable disease (Response Evaluation
      Criteria in Solid Tumors [RECIST]). (Phase 2)

      IV. To assess response to docetaxel and carboplatin in tumors with mutation of
      deoxyribonucleic acid (DNA) repair pathway genes (breast cancer [BRCA]1, BRCA2, ataxia
      telangiectasia mutated [ATM]). (Phase 2)

      V. To correlate the presence of DNA repair pathway mutations and copy number alterations in
      metastatic tissue versus in circulating tumor cells (CTC) and cell free DNA. (Phase 2)

      VI. To correlate changes in CTC number with PSA and radiographic response. (Phase 2)

      OUTLINE:

      Patients receive docetaxel intravenously (IV) over 30-60 minutes and carboplatin IV over
      30-60 minutes on day 1. Treatment repeats every 21 days for 10 courses in the absence of
      disease progression or unacceptable toxicity.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (docetaxel, carboplatin)ExperimentalPatients receive docetaxel IV over 30-60 minutes and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 10 courses in the absence of disease progression or unacceptable toxicity.
  • Carboplatin
  • Docetaxel

Eligibility Criteria

        Inclusion Criteria:

          -  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

          -  Histologically or cytologically confirmed carcinoma of the prostate (excluding
             neuroendocrine differentiation or squamous cell histology)

          -  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

          -  Castration resistant prostate cancer as defined by rising PSA when serum testosterone
             < 50 ng/ml (note: current testosterone results are not required if the potential
             subject has not missed any GnRH analogue/antagonist doses since their last result was
             received) 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

          -  Prior therapy with abiraterone, enzalutamide and/or docetaxel; there is no limit to
             the number of prior treatment regimens

          -  Presence of metastatic disease on scans

          -  Eastern Cooperative Oncology Group (ECOG) performance status of =< 1

          -  Life expectancy >= 12 weeks

          -  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)

          -  Absolute neutrophil count >= 1.5 x 10^9 cells/L

          -  Hemoglobin (Hgb) >= 9.0 g/dL

          -  Platelets >= 100,000 x 10^9/L

          -  Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 1.5 x upper limit
             of normal (ULN)

          -  Total bilirubin levels =< 1.5 x ULN

          -  Patients must have clear and documented evidence of biallelic inactivation BRCA1,
             BRCA2 or ATM by sequencing, for example University of Washington (UW)-Oncoplex, SU2C,
             or Foundation One testing and/or patients with clearly deleterious mutations of other
             genes involved in homologous DNA repair (e.g., partner and localizer of BRCA2 [PALB2],
             BRCA1-interacting protein 1 [BRIP1], etc.) by sequencing via UW-Oncoplex, SU2C, or
             Foundation One testing may be included at the investigator's discretion

        Exclusion Criteria:

          -  Currently receiving active therapy for other neoplastic disorders

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

          -  Known 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, if done

          -  Treatment with an investigational therapeutic within 30 days of cycle 1

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

          -  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:Proportion of patients with PSA decline by 50% from baseline according to Prostate Cancer Working Group 2 (PCWG2) criteria
Time Frame:Until disease progression or unacceptable toxicity, assessed up to 35 days after the last dose of study medication
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Median time to disease progression (Prostate Cancer Working Group 2 [PCWG2] criteria)
Time Frame:Until disease progression or unacceptable toxicity, assessed up to 35 days after the last dose of study medication
Safety Issue:
Description:
Measure:Number of patients with deoxyribonucleic acid (DNA) repair pathway mutations in circulating tumor cell (CTC) and cell free DNA
Time Frame:Baseline
Safety Issue:
Description:
Measure:Proportion of patients achieving 30% reduction in measurable disease from baseline, according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Time Frame:Until disease progression or unacceptable toxicity, assessed up to 35 days after the last dose of study medication
Safety Issue:
Description:
Measure:Proportion of patients with PSA decline by 90% from baseline (Prostate Cancer Working Group 2 [PCWG2] criteria)
Time Frame:Until disease progression or unacceptable toxicity, assessed up to 35 days after the last dose of study medication
Safety Issue:
Description:
Measure:Time to progression of bone lesions or measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Time Frame:Until disease progression or unacceptable toxicity, assessed up to 35 days after the last dose of study medication
Safety Issue:
Description:

Details

Phase:N/A
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Washington

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