Pembro With Radiation With or Without Olaparib

Prostate Cancer Clinical Trial

Official title:

Phase II Study of Pembrolizumab in Combination With Radiation With or Without Olaparib in Localized High-risk Prostate Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05568550
• Other study ID #: MCC-22-GU-80
• Status: Recruiting
• Phase: Phase 2
• Start date: July 27, 2023
• Est. completion date: July 2, 2029

Study information

• Verified date: May 2024
• Source: University of Kentucky
• Contact: Cary Osborne, RN,CCRC
• Phone: 859-218-2898
• Email: cary.osborne[@]uky.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: July 2, 2029
• Est. primary completion date: July 2, 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Biological:
• Pembrolizumab
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:
• Olaparib
200mg Olaparib will be given twice daily for a total of 3 cycles. Cycle 1 begins 21-days prior to radiation therapy.
• Androgen 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.

Radiation:
• Radiation 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

Country	Name	City	State
United States	University of Kentucky	Lexington	Kentucky
United States	Huntsman Cancer Institute	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
Zin W Myint	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	PSA Progression-Free Survival	PSA progression-free survival (PSA-PFS) stratified by PDL1 immunohistochemistry expression on baseline or /archival biopsy tissue, if tissue is available.	3 years (Pre-treatment baseline, cycle 3, 6 months or at disease progression)
Other	Correlation between clinical outcome and immune cell subtype.	Correlation between the clinical outcomes and changes in immune cell subtype frequencies (% CD4 T cells, % CD8 T cells, % naïve, effector memory, and T regulatory cells) immune functions (T cell ability to induce cytokine following stimulation).	3 years (Pre-treatment baseline, cycle 3, 6 months or at disease progression)
Other	Correlation between clinical outcome and cytokine levels.	Correlation between the serum cytokines (IL2, IL-10, and INF-?) and clinical outcomes.	3 years (Pre-treatment baseline, cycle 3, 6 months or at disease progression)
Other	Correlation between clinical outcomes and TCR repertories clonotypes.	Correlation between T cell receptor (TCR) repertories clonotypes and clinical outcomes.	3 years (Pre-treatment baseline, cycle 3, 6 months or at disease progression)
Other	Percent changes in plasma circulating tumor DNA	Percent changes in plasma circulating tumor DNA (ctDNA).	Baseline and on-treatment (6 months)
Primary	Clinical Response Rate	The proportion of patients who achieve a PSA nadir level of = 0.06ng/mL six months after completion of radiation therapy.	6 months
Secondary	Biochemical-Free Survival	Biochemical-free survival rate at 3 years as defined by Phoenix Criteria.	3 years
Secondary	Metastasis-Free Survival	Metastasis-free survival rate at 3 years as defined by RECIST v1.1 criteria.	3 years
Secondary	Time to Normalization of Serum Testosterone	Time from normalization is the date of first return to normal serum testosterone 270 ng/ml or greater after withdrawal of androgen deprivation therapy.	3 years
Secondary	Molecular Alterations in Homologous Recombination Repair Genes	Molecular alterations in the homologous recombination repair (HHR) genes.	3 years