Pembro With Radiation With or Without Olaparib

Trial Title: Pembro With Radiation With or Without Olaparib

NCT ID: NCT05568550

Condition: Prostate Cancer

Conditions: Official terms:
Prostatic Neoplasms
Pembrolizumab
Olaparib
Androgens

Conditions: Keywords:
immunotherapy
PARP
radiation
androgen deprivation therapy
ADT
PD-1

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Intervention model description: 1:1

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Biological
Intervention name: Pembrolizumab
Description: 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.
Arm group label: Arm 1 - Pembrolizumab and Olaparib
Arm group label: Arm 2 - Pembrolizumab

Other name: Keytruda

Intervention type: Drug
Intervention name: Olaparib
Description: 200mg Olaparib will be given twice daily for a total of 3 cycles. Cycle 1 begins 21-days prior to radiation therapy.
Arm group label: Arm 1 - Pembrolizumab and Olaparib

Other name: Lynparza

Intervention type: Drug
Intervention name: Androgen Deprivation Therapy
Description: 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.
Arm group label: Arm 1 - Pembrolizumab and Olaparib
Arm group label: Arm 2 - Pembrolizumab

Intervention type: Radiation
Intervention name: Radiation Therapy
Description: 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 group label: Arm 1 - Pembrolizumab and Olaparib
Arm group label: Arm 2 - Pembrolizumab

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.

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.

Criteria for 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

Gender: Male

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: University of Kentucky

Address:
City: Lexington
Zip: 40536
Country: United States

Status: Recruiting

Contact:
Last name: Yvonne Taul, RN,CCRC

Phone: 859-323-2354
Email: yvonne.taul@uky.edu

Contact backup:
Last name: Zin Myint, MD

Phone: 410236809
Email: zin.myint@uky.edu

Facility:
Name: Huntsman Cancer Institute

Address:
City: Salt Lake City
Zip: 84112
Country: United States

Status: Recruiting

Contact:
Last name: Benjamin Maughan, MD, PharmD

Phone: 801-581-2267
Email: benjamin.maughan@hci.utah.edu

Start date: July 27, 2023

Completion date: July 2, 2029

Lead sponsor:
Agency: Zin W Myint
Agency class: Other

Collaborator:
Agency: Merck Sharp & Dohme LLC
Agency class: Industry

Source: University of Kentucky

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05568550