Phase II Study of Pembrolizumab in Combination With Radiation With or Without Olaparib in Localized High-risk Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 64
- 试验地点
- 2
- 主要终点
- Clinical Response Rate
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Arm 1 - Pembrolizumab and Olaparib
Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab and Olaparib.
干预措施: Pembrolizumab (Biological)
Arm 1 - Pembrolizumab and Olaparib
Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab and Olaparib.
干预措施: Radiation Therapy (Radiation)
Arm 2 - Pembrolizumab
Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab.
干预措施: Androgen Deprivation Therapy (Drug)
Arm 2 - Pembrolizumab
Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab.
干预措施: Radiation Therapy (Radiation)
Arm 1 - Pembrolizumab and Olaparib
Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab and Olaparib.
干预措施: Androgen Deprivation Therapy (Drug)
Arm 1 - Pembrolizumab and Olaparib
Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab and Olaparib.
干预措施: Olaparib (Drug)
Arm 2 - Pembrolizumab
Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab.
干预措施: Pembrolizumab (Biological)
结局指标
主要结局
Clinical Response Rate
时间窗: 6 months
The proportion of patients who achieve a PSA nadir level of ≤ 0.06ng/mL six months after completion of radiation therapy.
次要结局
- Biochemical-Free Survival(3 years)
- Molecular Alterations in Homologous Recombination Repair Genes(3 years)
- Time to Normalization of Serum Testosterone(3 years)
- Metastasis-Free Survival(3 years)
研究者
Zin W Myint
Associate Professor
University of Kentucky