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

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ClinicalTrials.gov Identifier: NCT02985021
Recruitment Status : Recruiting
First Posted : December 7, 2016
Last Update Posted : December 10, 2018
Sponsor:
Collaborators:
Prostate Cancer Foundation
VA Puget Sound Health Care System
Information provided by (Responsible Party):
Seattle Institute for Biomedical and Clinical Research

Brief 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.

Condition or disease Intervention/treatment Phase
Hormone-Resistant Prostate Cancer Metastatic Prostate Carcinoma Recurrent Prostate Carcinoma Stage IV Prostate Cancer Drug: Carboplatin Drug: Docetaxel Phase 2

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)


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : November 2016
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Treatment (docetaxel, carboplatin)

Docetaxel 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.

Drug: Carboplatin
Chemotherapy
Other Name: Paraplatin

Drug: Docetaxel
Chemotherapy
Other Name: Taxotere




Primary Outcome Measures :
  1. 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. ]

Secondary Outcome Measures :
  1. 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. ]
  2. Response of measurable disease [ Time Frame: After 10 cycles (210 days), or more per Investigator discretion, or until disease progression or unacceptable toxicity. ]
  3. 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. ]
  4. 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. ]
  5. 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. ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02985021


Contacts
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Contact: Robert B Montgomery, MD 206-277-6878 Robert.Montgomery@med.va.gov
Contact: Akemi Miyamoto, BS 206-277-5598 Akemi.Miyamoto@va.gov

Locations
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United States, California
VA Greater Los Angeles - West LA Recruiting
Los Angeles, California, United States, 90073
Contact: Claudia Huiza, MA    310-478-3711 ext 44127    Claudia.Huiza@va.gov   
Principal Investigator: Matthew Rettig, MD         
United States, Michigan
VA Ann Arbor Health Care System Recruiting
Ann Arbor, Michigan, United States, 48105
Contact: Brittany Pannecouk, BS    734-845-3966    Brittany.Pannecouk@va.gov   
Principal Investigator: Ajjai Alva, MD         
United States, Washington
VA Puget Sound Health Care System Recruiting
Seattle, Washington, United States, 98108
Contact: Akemi Miyamoto, BS    206-277-5598    Akemi.Miyamoto@va.gov   
Principal Investigator: Robert B Montgomery, MD         
Sponsors and Collaborators
Seattle Institute for Biomedical and Clinical Research
Prostate Cancer Foundation
VA Puget Sound Health Care System
Investigators
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Principal Investigator: Robert B Montgomery, MD VA Puget Sound HCS
Principal Investigator: Matthew Rettig, MD VA Greater Los Angeles HCS

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Responsible Party: Seattle Institute for Biomedical and Clinical Research
ClinicalTrials.gov Identifier: NCT02985021     History of Changes
Other Study ID Numbers: PugetSoundVA
First Posted: December 7, 2016    Key Record Dates
Last Update Posted: December 10, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
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Carcinoma
Prostatic Neoplasms
DNA Repair-Deficiency Disorders
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Metabolic Diseases
Carboplatin
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action