Pembro With Radiation With or Without Olaparib

Официальное название

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

Обзор

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.

Подробное описание

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.

Due to slow accrual and feasibility concerns, the protocol was modified to single arm phase II study. All patients will receive definitive radiation therapy combined with ADT per institutional standards. In addition to concurrent ADT and radiation therapy, patients on this trial will also receive as follow: Pembrolizumab (17 cycles) combined with olaparib (the first three cycles). The remaining patients will be enrolled to Arm 1 only (i.e., Arm 2 usual care is closed to accrual upon Amendment 5 protocol).

Вмешательства

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

Первичные конечные точки

• Clinical Response Rate [Срок оценки: 6 months]

Вторичные конечные точки (4)

• Biochemical-Free Survival [Срок оценки: 3 years]
• Metastasis-Free Survival [Срок оценки: 3 years]
• Time to Normalization of Serum Testosterone [Срок оценки: 3 years]
• Molecular Alterations in Homologous Recombination Repair Genes [Срок оценки: 3 years]

Критерии участия

Критерии включения

• 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
• 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.

Критерии исключения

• 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 or pelvic nodes radiation.
• Previous or major surgery (colorectal anastomosis, total cystectomy, 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 2 центра

• University of Kentucky — Lexington
• Huntsman Cancer Institute — Salt Lake City

Идентификаторы

NCT: NCT05568550 · MCC-22-GU-80

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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