A Study of CHeckpoint Inhibitors in Men With prOgressive Metastatic Castrate Resistant Prostate Cancer Characterized by a Mismatch Repair Deficiency or Biallelic CDK12 Inactivation (NCT04104893)
🩺 Plain-English Summary (8th-Grade Level)
The primary objective is to assess the activity and efficacy of pembrolizumab, a checkpoint inhibitor, in Veterans with metastatic castration-resistant prostate cancer (mCRPC) characterized by either mismatch repair deficiency (dMMR) or biallelic inactivation of CDK12 (CDK12-/-). The secondary objectives involve determining the frequency with which dMMR and CDK12-/- occur in this patient population, as well as the effects of pembrolizumab on various clinical endpoints (time to PSA progression, maximal PSA response, time to initiation of alternative anti-neoplastic therapy, time to radiographic progression, overall survival, and safety and tolerability). Lastly, the study will compare the pre-treatment and at-progression metastatic tumor biopsies to investigate the molecular correlates of resistance and sensitivity to pembrolizumab via RNA-sequencing, exome-sequencing, selected protein analyses, and multiplexed immunofluorescence.
Who can join: To join this study, participants generally need to meet the listed inclusion criteria (24 items) and avoid the listed exclusions (22 items).
Location: San Francisco VA Medical Center, San Francisco, CA — San Francisco, California
📋 "Do I Qualify?" — 1-Minute Self Screener
Instant ChecklistCheck every box below. If you can check all of them, you may meet the study's basic screening requirements (final eligibility is confirmed by the site team).
Usually NOT eligible if any of the following apply:
- Exclusion Criteria:
- Brain metastases.
- Prior treatment with an anti-PD1, anti-PDL1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
- Anti-neoplastic therapies for prostate cancer must be completed \> 2 weeks prior to Day 1 (initiation of pembrolizumab); chemotherapy must be completed \> 4 weeks prior to Day 1.
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks \[could consider shorter interval for kinase inhibitors or other short half-life drugs\] prior to \[randomization /allocation\]. Note: Participants must have recovered from all AEs due to previous therapies to Grade 1 or baseline. Participants with Grade 2 neuropathy may be eligible.
- Herbal and non-herbal products that may decrease PSA levels other than medical castration and megestrol (up to 40 mg/day is allowed) for hot flashes.
- Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation ( 2 weeks of radiotherapy) to non-CNS disease.
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
- If a subject has undergone major surgery, they must have recovered adequately from the toxicities or complications from the intervention within 4 weeks prior to starting therapy.
- History of non-prostate active malignancy requiring treatment in the 24 months prior to Day 1 except for non-muscle invasive urothelial cancer and non-melanoma skin cancer.
- Active infection or conditions requiring treatment with antibiotics.
- Immunosuppressive doses of systemic medications, such as corticosteroids (doses \> 10 mg/day prednisone or equivalent), within 2 weeks of Day 1.
🔍 Extracted verbatim from the official NIH eligibility criteria. Always confirm with the study coordinator.
📍 All Participating Trial Locations (13 Sites)
- San Francisco VA Medical Center, San Francisco, CA — San Francisco, California
- VA Greater Los Angeles Healthcare System, West Los Angeles, CA — West Los Angeles, California
- Washington DC VA Medical Center, Washington, DC — Washington D.C., District of Columbia
- Bay Pines VA Healthcare System, Pay Pines, FL — Bay Pines, Florida
- Jesse Brown VA Medical Center, Chicago, IL — Chicago, Illinois
- VA Ann Arbor Healthcare System, Ann Arbor, MI — Ann Arbor, Michigan
- Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY — New York, New York
- James J. Peters VA Medical Center, Bronx, NY — The Bronx, New York
- Durham VA Medical Center, Durham, NC — Durham, North Carolina
- VA Portland Health Care System, Portland, OR — Portland, Oregon
- Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA — Philadelphia, Pennsylvania
- Hunter Holmes McGuire VA Medical Center, Richmond, VA — Richmond, Virginia
- VA Puget Sound Health Care System Seattle Division, Seattle, WA — Seattle, Washington
💰 Cost, Insurance & Patient Rights
- 100% Free Items: The investigational treatment and protocol-required procedures are supplied at zero cost by the sponsor.
- Routine Patient Care: Under federal law (ACA § 2709) and many state statutes, routine care costs are covered during participation.
- Voluntary Participation: You may withdraw at any time without affecting your standard medical care.