Phase II Study of Pembrolizumab in Combination With Radiation With or Without Olaparib in Localized High-risk Prostate Cancer
Zin W Myint
Summary
This trial will evaluate whether the immune-sensitizing effects of immunotherapy (Pembrolizumab) and radiation with or without a PARP-inhibitor (Olaparib) will increase the effects of immunotherapy in men with high-risk localized prostate cancer.
Description
Immunotherapy and PARP-inhibitor are known to have radio-sensitizing effects when combined with radiation therapy. In addition, the combination with PARP-inhibitor and radiation can increase neoantigen expression, cytotoxic lymphocyte infiltration within the tumor microenvironment and increased immune stimulating cytokine concentration. Thus, there is a potential synergy of combining immunotherapy and PARP-inhibitor. This is a phase 2 randomized 1:1 study. Subjects will be randomized to one arm (pembro + PARPi + standard of care therapy which is definitive radiation therapy combined with horm…
Eligibility
- Age range
- 18+ years
- Sex
- Male
- Healthy volunteers
- No
Inclusion Criteria: * Male participants with histologically confirmed adenocarcinoma of the prostate * High-risk / very high-risk status per NCCN guidelines * ECOG performance status 0 to 1 * Regional lymph nodes are allowed. * Agree to use contraception during the treatment period and for at least 120 days after the last dose of study intervention and refrain from donating sperm during this period. * Ability to understand and the willingness to sign a written informed consent document. * Adequate organ and marrow function * Prior pharmacologic androgen ablation for prostate cancer is allowed…
Interventions
- BiologicalPembrolizumab
Pembrolizumab will be delivered via IV at 200mg on day 1 of each 3-week cycle for approximately 12 months. Cycle 1 begins 21 days prior to radiation therapy and cycles 2-17 are administered during and after radiation therapy.
- DrugOlaparib
200mg Olaparib will be given twice daily for a total of 3 cycles. Cycle 1 begins 21-days prior to radiation therapy.
- DrugAndrogen Deprivation Therapy
Androgen Deprivation Therapy (either LHRH agonist or LHRH antagonist) as per treating physician choice will be allowed within 3 months prior to randomization. Duration is per institutional standards.
- RadiationRadiation Therapy
Definitive radiation (total dose and fractions) will be dosed per institutional standards. Definitive radiation may include external beam radiation therapy with or without brachytherapy, based on NCCN risk score and as per treating physicians.
Locations (2)
- University of KentuckyLexington, Kentucky
- Huntsman Cancer InstituteSalt Lake City, Utah