Adaptive Androgen Deprivation and Docetaxel in Metastatic Castration Sensitive Prostate Cancer

A Phase IIA Study of Adaptive Androgen Deprivation and Docetaxel in Metastatic Castration Sensitive Prostate Cancer

This is a prospective single center phase IIa open label nonrandomized study, which aims to test the hypothesis that the duration of castration sensitive phase of stage IV prostate cancer can be prolonged with adaptive androgen deprivation therapy (ADT) and Docetaxel.

Inclusion Criteria:

• Biopsy proven prostate cancer and the diagnosis can be established through either prostate biopsy or biopsy of a metastatic lesion.
• No androgen deprivation therapy (ADT) with LHRH analog for more than 4 weeks after the diagnosis of metastatic prostate cancer. Prior ADT in the non-metastatic setting is allowed if it was given > 2 years prior to the diagnosis of metastatic prostate cancer.
• Achieved >50% PSA decline and <4 ng/ml PSA after the run-in period.
• Adequate organ function with absolute neutrophil count > 1000/l, Hb > 10 g/dl, Platelet > 100,000/l, Creatinine and liver enzymes within 1.5 folds of upper limits of normal.
• No uncontrolled arrhythmia; patients with h/o myocardia infarction or history of congestive heart failure, need to have estimated left ventricle ejection fraction above 40% either on echocardiogram or MUGA scan within 6 months of study enrollment.
• ECOG performance status 0-1.
• Non-sterilized men who are sexually active with a female partner of childbearing potential treated or enrolled on this protocol must agree to use adequate contraception prior to the study, for the duration of study participation, and for 6 weeks after last dose of ARSI or docetaxel administration.
• Ability to understand and the willingness to sign a written informed consent document or have a legally authorized representative sign on the subject's behalf. Stated willingness to comply with all study procedures and availability for the duration of the study.

Exclusion Criteria:

• Prior treatments with TAK-700/Orteronel, abiraterone, apalutamide or enzalutamide.
• Surgical castration.
• Documented liver or brain metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxel (including any drugs formulated with polysorbate 80), or LHRH analog (e.g., leuprolide, triptorelin, relugolix, degarelix)
• Treatment with any investigational compound within 30 days prior to the first dose of study drugs.
• Diagnosis or treatment for another systemic malignancy within 2 years before the first dose of LHRH analog, or previously diagnosed with another malignancy & have any evidence of residual disease. Patients with early-stage skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Subjects with delayed healing of wounds, ulcers, and/or bone fractures.