Clinical trial NCT05568550: Pembro With Radiation With or Without Olaparib
Official title: Phase II Study of Pembrolizumab in Combination With Radiation With or Without Olaparib in Localized High-risk Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: immunotherapy
PARP
radiation
androgen deprivation therapy
ADT
PD-1
Lead sponsor: University of Kentucky
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2022-10-05
Enrollment: 64
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1
Primary purpose: TREATMENT

Brief 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.

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
* 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 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 M1 disease

Primary outcomes:
measure: Clinical Response Rate
timeFrame: 6 months
Secondary outcomes:
measure: Biochemical-Free Survival
timeFrame: 3 years
measure: Metastasis-Free Survival
timeFrame: 3 years
measure: Time to Normalization of Serum Testosterone
timeFrame: 3 years
measure: Molecular Alterations in Homologous Recombination Repair Genes
timeFrame: 3 years
Other outcomes:
measure: PSA Progression-Free Survival
timeFrame: 3 years (Pre-treatment baseline, cycle 3, 6 months or at disease progression)
measure: Correlation between clinical outcome and immune cell subtype.
timeFrame: 3 years (Pre-treatment baseline, cycle 3, 6 months or at disease progression)
measure: Correlation between clinical outcome and cytokine levels.
timeFrame: 3 years (Pre-treatment baseline, cycle 3, 6 months or at disease progression)
measure: Correlation between clinical outcomes and TCR repertories clonotypes.
timeFrame: 3 years (Pre-treatment baseline, cycle 3, 6 months or at disease progression)
measure: Percent changes in plasma circulating tumor DNA
timeFrame: Baseline and on-treatment (6 months)
Locations:
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
Study officials:
affiliation: University of Kentucky
name: Zin W Myint, MD
role: PRINCIPAL_INVESTIGATOR
References: