Pembro With Radiation With or Without Olaparib

Clinicaltrials.gov ID: NCT05568550
db-list-check Status RECRUITING
b-loader Phase PHASE2
b-people Age ≥ 18 Years
b-bullseye-arrow Enrollments 64

Conditions

Prostate Cancer

Drugs

Olaparib, Androgen Deprivation Therapy

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.

Locations

2 locations Found with status Recruiting

Status

  • RECRUITING

Contact Person

Principal Investigator

  • Zin W Myint, MD

Status

  • RECRUITING

Contact Person

Principal Investigator

  • Zin W Myint, MD

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

Study Plan

Arm 1 - Pembrolizumab and Olaparib

EXPERIMENTAL

Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab and Olaparib.

  • BIOLOGICAL:

    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.
  • DRUG:

    Olaparib

    Description:

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

    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.
  • RADIATION:

    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 2 - Pembrolizumab

EXPERIMENTAL

Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab.

  • BIOLOGICAL:

    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.
  • DRUG:

    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.
  • RADIATION:

    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.

Outcome Measures

Primary Outcome Measures

Clinical Response Rate

Time Frame: 6 months

Secondary Outcome Measures

Biochemical-Free Survival

Time Frame: 3 years

Metastasis-Free Survival

Time Frame: 3 years

Time to Normalization of Serum Testosterone

Time Frame: 3 years

Molecular Alterations in Homologous Recombination Repair Genes

Time Frame: 3 years

Timeline

  • Last Updated
    May 3, 2024
  • Start Date
    October 5, 2022
  • Today
    February 5, 2025
  • Completion Date ( Estimated )
    July 2, 2029

Similar Trials

light-list-check RECRUITING light-blue-people 21 - 64 Years
light-list-check RECRUITING light-blue-people ≥ 18 Years
light-list-check RECRUITING light-blue-people ≥ 65 Years