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

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.

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