A Randomized Phase II Study of Chemoradiation and Pembrolizumab for Locally Advanced Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 94
- 试验地点
- 8
- 主要终点
- Number of Participants With Dose Limiting Toxicities
研究概览
简要总结
The purpose of this study is to evaluate the safety and effectiveness of immunotherapy in combination with chemotherapy and radiation (chemoradiation) for the treatment of advanced cervical cancer. Pembrolizumab, a type of immunotherapy called a checkpoint inhibitor, will be administered after or during chemoradiation.
详细描述
Primary: (1) To estimate the immunologic effects, as assessed in the tumor & PBMC, of both sequential and concurrent administration of pembrolizumab to CRT. Change between pre and post measurements of HPV E2, E7 specific CD8+ T cells, regulatory FoxP3+ T cells (Tregs) and the ratio of CD8+ T cells to Tregs are the immune measurements of primary interest. (2) To determine the safety of concurrent chemoradiation in combination with pembrolizumab for the treatment of locally advanced cervical cancer. Secondary: (1) To estimate rates of complete metabolic response on PET/CT imaging obtained 12 weeks after CRT.
(2) To estimate rates of distant metastasis as the first site of recurrence for patients.
(3) To estimate the influence of concurrent and consolidative MK-3475 on levels of plasminogen activator inhibitor-1 (PAI-1), a marker of immunosuppressive TGF-B.
(4) To estimate the influence of concurrent and consolidative MK-3475 on levels of IDO, an enzyme that depletes tryptophan, which is essential for T-cell function.
(5) To estimate the influence of concurrent and consolidative MK-3475 on levels of MHC class I (CD8+ T cell ligand) and MICA (NK ligand), as measured by MHC.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Confirmed cervical cancer.
- •Must have adequate organ function.
排除标准
- •Subject is pregnant.
- •Recurrent cervical cancer.
- •Distant metastases.
- •Malignancy within the last 5 years; basal cell carcinoma or squamous cell carcinoma of the skin that has undergone potentially curative therapy is permissable.
- •Subject has had prior radiation, chemotherapy, targeted therapy, or investigational therapy for cervical cancer.
- •Subject has a immunodeficiency.
- •Known history of HIV, Hepatitis B, Hepatitis C, TB, or inflammatory bowel disease.
- •Hypersensitivity to pembrolizumab or similar drugs.
- •Subject has an active autoimmune disease in the past 2 years.
- •Known history of non-infectious pneumonitis.
- •Subject has an active infection.
- •Subject has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases are permissible. Talk to Study Contact for specifics.
研究组 & 干预措施
Following chemoradiation
Subjects will receive standard chemotherapy weekly and 4-6 fractions of brachytherapy radiation for 5-6 weeks. After chemoradiation is complete, subjects will receive the study drug, pembrolizumab.
干预措施: Pembrolizumab (Drug)
Following chemoradiation
Subjects will receive standard chemotherapy weekly and 4-6 fractions of brachytherapy radiation for 5-6 weeks. After chemoradiation is complete, subjects will receive the study drug, pembrolizumab.
干预措施: Brachytherapy (Radiation)
Following chemoradiation
Subjects will receive standard chemotherapy weekly and 4-6 fractions of brachytherapy radiation for 5-6 weeks. After chemoradiation is complete, subjects will receive the study drug, pembrolizumab.
干预措施: Cisplatin (Drug)
Concurrent to chemoradiation
Subjects will receive standard chemotherapy weekly and 4-6 fractions of brachytherapy radiation for 5-6 weeks. While subjects are receiving chemotherapy and radiation, they will also receive the study drug, pembrolizumab.
干预措施: Pembrolizumab (Drug)
Concurrent to chemoradiation
Subjects will receive standard chemotherapy weekly and 4-6 fractions of brachytherapy radiation for 5-6 weeks. While subjects are receiving chemotherapy and radiation, they will also receive the study drug, pembrolizumab.
干预措施: Brachytherapy (Radiation)
Concurrent to chemoradiation
Subjects will receive standard chemotherapy weekly and 4-6 fractions of brachytherapy radiation for 5-6 weeks. While subjects are receiving chemotherapy and radiation, they will also receive the study drug, pembrolizumab.
干预措施: Cisplatin (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities
时间窗: From start of treatment until 12 weeks post-chemoradiation
To determine the safety of concurrent chemoradiation in combination with pembrolizumab for the treatment of locally advanced cervical cancer
Change in Immunologic Markers Following Combination of Study Drug With Chemoradiation
时间窗: 12 weeks post-chemoradiation
Expression of immune markers measured at pre and post administration of study drug with chemoradiation will be compared, analyzed and enumerated using QuPath software to provide a cell #/mm2 (not per high power field) and the ratio of CD8+ cells:FoxP3+ cells/mm2 was calculated.
次要结局
- Progression Free Survival(From start of treatment until up to 5 years following end of treatment)
- Metabolic Response Rate on PET/CT Imaging(12 weeks after chemotherapy)
- Overall Survival(From start of treatment until up to 5 years following end of treatment)
- Incidence of Distant Metastases(From start of treatment until up to 5 years following end of treatment)
研究者
Linda R Duska
Associate Professor, Division of Gynecology Oncology
University of Virginia