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.
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
Drug | Synonyms | Arms |
---|
Carboplatin | Paraplatin | Treatment (docetaxel, carboplatin) |
Docetaxel | Taxotere | Treatment (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
Name | Type | Description | Interventions |
---|
Treatment (docetaxel, carboplatin) | Experimental | 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. | |
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 |
Last Updated