Pembro With Radiation With or Without Olaparib
Primary Purpose
Prostate Cancer
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pembrolizumab
Olaparib
Androgen Deprivation Therapy
Radiation Therapy
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring immunotherapy, PARP, radiation, androgen deprivation therapy, ADT, PD-1
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
Sites / Locations
- University of KentuckyRecruiting
- Huntsman Cancer Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm 1 - Pembrolizumab and Olaparib
Arm 2 - Pembrolizumab
Arm Description
Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab and Olaparib.
Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab.
Outcomes
Primary Outcome Measures
Clinical Response Rate
The proportion of patients who achieve a PSA nadir level of ≤ 0.06ng/mL six months after completion of radiation therapy.
Secondary Outcome Measures
Biochemical-Free Survival
Biochemical-free survival rate at 3 years as defined by Phoenix Criteria.
Metastasis-Free Survival
Metastasis-free survival rate at 3 years as defined by RECIST v1.1 criteria.
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.
Molecular Alterations in Homologous Recombination Repair Genes
Molecular alterations in the homologous recombination repair (HHR) genes.
Full Information
NCT ID
NCT05568550
First Posted
September 29, 2022
Last Updated
July 27, 2023
Sponsor
Zin W Myint
Collaborators
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT05568550
Brief Title
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
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 27, 2023 (Actual)
Primary Completion Date
July 2, 2026 (Anticipated)
Study Completion Date
July 2, 2029 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Zin W Myint
Collaborators
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
immunotherapy, PARP, radiation, androgen deprivation therapy, ADT, PD-1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
1:1
Masking
None (Open Label)
Allocation
Randomized
Enrollment
64 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm 1 - Pembrolizumab and Olaparib
Arm Type
Experimental
Arm Description
Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab and Olaparib.
Arm Title
Arm 2 - Pembrolizumab
Arm Type
Experimental
Arm Description
Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab.
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda
Intervention 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.
Intervention Type
Drug
Intervention Name(s)
Olaparib
Other Intervention Name(s)
Lynparza
Intervention Description
200mg Olaparib will be given twice daily for a total of 3 cycles. Cycle 1 begins 21-days prior to radiation therapy.
Intervention Type
Drug
Intervention Name(s)
Androgen Deprivation Therapy
Intervention 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.
Intervention Type
Radiation
Intervention Name(s)
Radiation Therapy
Intervention 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.
Primary Outcome Measure Information:
Title
Clinical Response Rate
Description
The proportion of patients who achieve a PSA nadir level of ≤ 0.06ng/mL six months after completion of radiation therapy.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Biochemical-Free Survival
Description
Biochemical-free survival rate at 3 years as defined by Phoenix Criteria.
Time Frame
3 years
Title
Metastasis-Free Survival
Description
Metastasis-free survival rate at 3 years as defined by RECIST v1.1 criteria.
Time Frame
3 years
Title
Time to Normalization of Serum Testosterone
Description
Time from normalization is the date of first return to normal serum testosterone 270 ng/ml or greater after withdrawal of androgen deprivation therapy.
Time Frame
3 years
Title
Molecular Alterations in Homologous Recombination Repair Genes
Description
Molecular alterations in the homologous recombination repair (HHR) genes.
Time Frame
3 years
Other Pre-specified Outcome Measures:
Title
PSA Progression-Free Survival
Description
PSA progression-free survival (PSA-PFS) stratified by PDL1 immunohistochemistry expression on baseline or /archival biopsy tissue, if tissue is available.
Time Frame
3 years (Pre-treatment baseline, cycle 3, 6 months or at disease progression)
Title
Correlation between clinical outcome and immune cell subtype.
Description
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).
Time Frame
3 years (Pre-treatment baseline, cycle 3, 6 months or at disease progression)
Title
Correlation between clinical outcome and cytokine levels.
Description
Correlation between the serum cytokines (IL2, IL-10, and INF-γ) and clinical outcomes.
Time Frame
3 years (Pre-treatment baseline, cycle 3, 6 months or at disease progression)
Title
Correlation between clinical outcomes and TCR repertories clonotypes.
Description
Correlation between T cell receptor (TCR) repertories clonotypes and clinical outcomes.
Time Frame
3 years (Pre-treatment baseline, cycle 3, 6 months or at disease progression)
Title
Percent changes in plasma circulating tumor DNA
Description
Percent changes in plasma circulating tumor DNA (ctDNA).
Time Frame
Baseline and on-treatment (6 months)
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yvonne Taul, RN,CCRC
Phone
859-323-2354
Email
Yvonne.Taul@uky.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zin W Myint, MD
Organizational Affiliation
University of Kentucky
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yvonne Taul, RN,CCRC
Phone
859-323-2354
Email
yvonne.taul@uky.edu
Facility Name
Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Benjamin Maughan, MD, PharmD
Phone
801-581-2267
Email
benjamin.maughan@hci.utah.edu
12. IPD Sharing Statement
Plan to Share IPD
No
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