Trials / Withdrawn

WithdrawnNCT06528210

Pembrolizumab With Androgen Deprivation Therapy and Radiotherapy for the Treatment of Patients With High Risk Localized Prostate Cancer

Single-Arm, Open-Label, Phase II Study of Pembrolizumab Plus Androgen Deprivation Therapy (ADT) in Combination With Radiotherapy (RT) for High Risk Localized Prostate Cancer

Status: Withdrawn
Phase: Phase 2
Study type: Interventional
Enrollment: 0 (actual)

Sponsor: OHSU Knight Cancer Institute · Academic / Other
Sex: Male
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase II trial tests how well pembrolizumab along with standard of care androgen deprivation therapy, with bicalutamide and gonadotropin releasing hormone agonist, and radiotherapy for the treatment of patients with high risk prostate cancer that has not spread to other parts of the body (localized). A monoclonal antibody, such as pembrolizumab, is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Bicalutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of tumor cells. Gonadotropin-releasing hormone agonists prevent the body from making luteinizing hormone-releasing hormone (LHRH) and luteinizing hormone (LH). This causes the testicles to stop making testosterone (a male hormone) in men and may stop the growth of prostate cancer cells that need testosterone to grow. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Giving pembrolizumab with androgen deprivation therapy and radiotherapy may kill more tumor cells in patients with high risk localized prostate cancer.

Detailed description

PRIMARY OBJECTIVES: I. Determine the rate of prostate biopsy positivity at 6 months (mo.) in patients receiving pembrolizumab plus androgen deprivation therapy (ADT) in combination with radiotherapy. II. Determine the safety of pembrolizumab in combination with ADT and radiotherapy. SECONDARY OBJECTIVES: I. Compare 6-month post-treatment biopsy positive rate in patients stratified by pre-treatment prostate infiltrating T-cell PD-1 and PD-L1 expression. II. Measures changes in health related quality of life (HRQOL). III. Determine the rate of grade 3 or higher Immune-related adverse events (irAEs). IV. Determine the rate of biochemical relapse-free survival (bRFS) stratified by tumor PD-1 and PD-L1 expression. EXPLORATORY OBJECTIVES: I. Determine the time to cancer-directed treatment in subjects undergoing experimental treatment. II. Determine the 5-year rate of biochemical relapse-free survival (\[bRFS,\] i.e. prostate specific antigen \[PSA\] \> nadir + 2 ng/mL) III. Determine the nadir biochemical response rate (nadir PSA ≤ 0.5 ng/mL) IV. Determine the clinical and bRFS at five years. V. Report safety and tolerability of pembrolizumab, defined as pembrolizumab related adverse event of any grade and drug dose modification. VI. Determine metastases-free survival based on conventional imaging (not positron emission tomography \[PET\] based). VII. Determine the serum castration recovery rate (testosterone above 50 ng/dL) VIII. Determine the serum testosterone recovery rate (testosterone above 200 ng/dL) IX. Assess the effect of pembrolizumab combined with ADT + radiation therapy (RT) on serum, blood and tissue markers of the immune response. X. Correlate changes in markers of inflammatory response with clinical outcomes including post-treatment biopsy rate, PSA response and tumor free survival. XI. Correlate baseline prostate specific membrane antigen (PSMA) scan findings with efficacy endpoints. XII. Changes from pre- to post-treatment serum, peripheral blood mononuclear cells (PBMC), blood, microbial and tissue markers of the immune response. XIII. Correlation of changes in markers of inflammatory response with clinical outcomes including biopsy-complete response, PSA response and disease free survival. XIV. Determine the rate of local tumor eradication at 12 months for those who had persistent tumor at 6 months. OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for 51 weeks in the absence of disease progression or unacceptable toxicity. Patients receive standard of care ADT with GNRH agonist (leuprolide, goserelin, triptorelin) or GNRH antagonist (relugolix, degarelix) given orally (PO), subcutaneously (sub-Q) or via sub-Q implant for a total of 24 months, bicalutamide PO once per day (QD) for 6 months or up to 24 months per the discretion of the treating physician and radiation therapy per standard of care. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo bone scan and/or computed tomography (CT) scan/ magnetic resonance imaging (MRI) during screening and prostate biopsy and blood sample collection throughout the study. After completion of study therapy, patients are followed up at 30 days and yearly thereafter.

Conditions

Interventions

Type	Name	Description
DRUG	Gonadotropin Releasing Hormone Agonists and Antagonists	Given PO, IM, Sub-Q injection or Sub-Q implant
DRUG	Bicalutamide	Given PO
PROCEDURE	Biopsy Procedure	Undergo prostate biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Computed Tomography	Undergo CT scan
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
BIOLOGICAL	Pembrolizumab	Given IV
OTHER	Questionnaire Administration	Ancillary study
RADIATION	Radiation Therapy	Undergo radiation therapy
PROCEDURE	Bone Scan	Undergo bone scan

Timeline

Start date: 2025-04-16
Primary completion: 2026-06-01
Completion: 2028-06-01
First posted: 2024-07-30
Last updated: 2025-09-23

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT06528210. Inclusion in this directory is not an endorsement.