Overview
This is an open-label, non-randomized, exploratory platform protocol designed to assess the safety and antitumor activity of epigenetic therapies in participants with localized prostate cancer who are undergoing radical prostatectomy. The epigenetic therapy is intended to increase the sensitivity of the underlying tumor to the patient's immune system. The platform study will evaluate safety, biomarkers, and clinical activity of an epigenetic therapy. The particular details relevant to each module within this platform study will be provided as appendices to the core protocol.
Description
The study lead investigators will modify and/or add new therapies to the protocol as data emerge from this and other trials. Participants must provide consent for archival biopsy tissue prior to surgery for prostate cancer and must consent to allowing for use of their surgical specimens from biopsy and prostatectomy for biomarker characterization. Given the absence of data in this setting, this pilot proposes this experience with up to 4 weeks of epigenetic agents at doses known to be clinically safe and effective at inducing clinical activity.
Participants will be assigned to receive one of the study interventions and will be monitored for safety and response. The duration of epigenetic therapy will be dependent on the treatment administered and will continue for the duration described in the cohort appendix for each respective combination, unless the participant: is no longer clinically benefiting (NLCB, as evidenced by symptomatic or radiographic disease progression and/or clinical deterioration); experiences any toxicity meeting specified discontinuation criteria (as described in the cohort appendix for each respective combination) or unacceptable toxicity in the best clinical discretion of the treating physician (i.e., Investigator discretion); reaches the maximum duration of study intervention; or withdraws consent.
Eligibility
Inclusion Criteria
- Men electing to undergo radical prostatectomy with preoperative tissue available.
- Age ≥18 years
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
- Adequate organ function defined by:
- AST and ALT < 2.5 x ULN
- Total bilirubin < 1.5 x ULN
- Platelets > 90 x 1000/μL
- Hemoglobin (Hgb) > 8.5 g/dL
- Serum Creatinine (Cr) <1.5 x ULN or eGFR > 30 mL/min
- People with partners of childbearing potential in circumstances that may result in
the pregnancy, must have had a successful vasectomy (with medically confirmed lack of sperm that are alive) OR must either practice complete abstinence or agree to use adequate contraception (latex or synthetic condom during sexual contact with a female of childbearing potential) from the start of study treatment until 3 months following last dose of study intervention. Subjects should not donate sperm on study, during interruptions in treatment and for 3 months following completion of study drug treatment.
- Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
Exclusion Criteria
- Active intercurrent illness or malignancy requiring therapy outside of prostate cancer.
- Other anti-cancer therapy (chemotherapy, hormonal therapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization)
- Currently participating in a study using an investigational, medicinal anti-cancer agent within 4 weeks prior to first dose of epigenetic therapy.