Docetaxel and Carboplatin in Treating Patients With Metastatic, Castration Resistant Prostate Cancer Containing Inactivated Genes in the BRCA 1/2 Pathway
Keywords
Abstract
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.
Dates
| Last Verified: | 05/31/2020 |
| First Submitted: | 10/12/2015 |
| Estimated Enrollment Submitted: | 11/03/2015 |
| First Posted: | 11/05/2015 |
| Last Update Submitted: | 06/14/2020 |
| Last Update Posted: | 06/15/2020 |
| Actual Study Start Date: | 01/25/2016 |
| Estimated Primary Completion Date: | 06/29/2021 |
| Estimated Study Completion Date: | 06/29/2021 |
Condition or disease
Intervention/treatment
Drug: Treatment (docetaxel, carboplatin)
Drug: Treatment (docetaxel, carboplatin)
Other: Treatment (docetaxel, carboplatin)
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Experimental: Treatment (docetaxel, carboplatin) Patients 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. | Drug: Treatment (docetaxel, carboplatin) Given IV |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | Male |
| Accepts Healthy Volunteers | Yes |
| 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 |
Outcome
Primary Outcome Measures
1. Proportion of patients with PSA decline by 50% from baseline according to Prostate Cancer Working Group 2 (PCWG2) criteria [Until disease progression or unacceptable toxicity, assessed up to 35 days after the last dose of study medication]
Secondary Outcome Measures
1. Median time to disease progression (Prostate Cancer Working Group 2 [PCWG2] criteria) [Until disease progression or unacceptable toxicity, assessed up to 35 days after the last dose of study medication]
2. Number of patients with deoxyribonucleic acid (DNA) repair pathway mutations in circulating tumor cell (CTC) and cell free DNA [Baseline]
3. Proportion of patients achieving 30% reduction in measurable disease from baseline, according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 [Until disease progression or unacceptable toxicity, assessed up to 35 days after the last dose of study medication]
4. Proportion of patients with PSA decline by 90% from baseline (Prostate Cancer Working Group 2 [PCWG2] criteria) [Until disease progression or unacceptable toxicity, assessed up to 35 days after the last dose of study medication]
5. Time to progression of bone lesions or measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 [Until disease progression or unacceptable toxicity, assessed up to 35 days after the last dose of study medication]
