Pembro With Radiation With or Without Olaparib
Conditions
Prostate CancerDrugs
Olaparib, Androgen Deprivation TherapySummary
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.
Detailed 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 hormonal therapy) vs. another arm (pembro + standard of care therapy). All subjects will receive adjuvant immunotherapy for one year once they are done with definitive radiation treatment.
Locations
2 locations Found with status Recruiting
Status
- RECRUITING
Contact Person
- Yvonne Taul, RN,CCRC
- 859-323-2354
- [email protected]
Principal Investigator
- Zin W Myint, MD
Status
- RECRUITING
Contact Person
- Benjamin Maughan, MD, PharmD
- 801-581-2267
- [email protected]
Principal Investigator
- Zin W Myint, MD
Eligibility Criteria
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
* No pelvic nodes >2 cm in long axis as established by CT imaging
* 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 only if the onset of androgen ablation is ≤90 days prior to the date of registration
* Prior 5-alpha reductase inhibitor (for example, finasteride) for prostatic hypertrophy is allowed if discontinued at least 60 days prior to registration.
* Known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.
Exclusion Criteria:
* PSA > 150ng/ml
* Prior hormonal therapy with LHRH agonists (e.g., Lupron) and LHRH antagonists (e.g., Degarelix)for prostate cancer continuously for more than 90-days prior to study enrollment.
* Prior radiation to the prostate. Previous pelvic RT or major surgery (colorectal anastomosis, total cystectomy, radical prostatectomy, TURP, etc.). History of Ulcerative proctitis.
* Concurrent active, additional malignancy in the last 2 years.
* Prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to randomization.
* Patients with distant metastases
Study Plan
Arm 1 - Pembrolizumab and Olaparib
EXPERIMENTAL
Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab and Olaparib.
BIOLOGICAL:
PembrolizumabDescription:
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.DRUG:
OlaparibDescription:
200mg Olaparib will be given twice daily for a total of 3 cycles. Cycle 1 begins 21-days prior to radiation therapy.DRUG:
Androgen Deprivation TherapyDescription:
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.RADIATION:
Radiation TherapyDescription:
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.
Arm 2 - Pembrolizumab
EXPERIMENTAL
Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab.
BIOLOGICAL:
PembrolizumabDescription:
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.DRUG:
Androgen Deprivation TherapyDescription:
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.RADIATION:
Radiation TherapyDescription:
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.
Outcome Measures
Primary Outcome Measures
Clinical Response Rate
Secondary Outcome Measures
Biochemical-Free Survival
Metastasis-Free Survival
Time to Normalization of Serum Testosterone
Molecular Alterations in Homologous Recombination Repair Genes
Timeline
Last Updated
May 3, 2024Start Date
October 5, 2022Today
January 16, 2025Completion Date ( Estimated )
July 2, 2029
Sponsors of this trial
Lead Sponsor
Zin W MyintCollaborating Sponsors
Merck Sharp & Dohme LLC