A Pilot Study of Immune Checkpoint Inhibition (Durvalumab With or Without Tremelimumab) in Combination With Radiation Therapy in Patients With Unresectable Pancreatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 65
- 试验地点
- 2
- 主要终点
- Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug
研究概览
简要总结
Background:
- Stereotactic body radiation therapy (SBRT) is used to treat cancer. It is a way of giving very focused beams of radiation to tumors. Researchers think that the drugs being used in this study might work better when combined with SBRT in people with pancreatic cancer.
Objective:
- To study the safety and effectiveness of Durvalumab (MEDI4736) and/or tremelimumab with SBRT.
Eligibility:
- People 18 and older who have pancreatic cancer that has not responded or to chemotherapy. They must be candidates for radiation but not resection.
Design:
- Participants will be screened with medical history and physical exam. They will have blood tests. Their tumor will be measured using computerized tomography (CT) or magnetic resonance imaging (MRI).
- Participants will have their tumor biopsied with a needle. They will have also have a biopsy after cycle 1.
- Participants will get 1 or 2 drugs in combination with the SBRT.
- For MEDI4736, the duration of each cycle will be 28-days. Participants will get the drug through an intravenous (IV) infusion twice in each cycle (Days 1 and 15).
- For tremelimumab, the duration of the first 6 cycles will each last 28 days. Then the duration of the last 3 cycles will change to 12 weeks. Participants will get the drug through an IV once in each cycle.
- All participants will have SBRT. Some will get 1 dose of radiation and some will get 5. CT scans will map their tumor.
- Participants will have medical history, physical exam, and blood tests in each cycle. They will have a CT scan or MRI every 8 weeks. Cycles will continue for up to 12 months.
- Participants will be contacted yearly for follow-up.
详细描述
Background:
Tremelimumab is a monoclonal antibody against cytotoxic T-lymphocyte-associated protein 4 (CTLA4). Anti-CTLA4 therapy has been shown to enhance anti-tumor immunity by blocking tumor-induced immune suppression of cytotoxic T cells.
Durvalumab is a human monoclonal antibody directed against Programmed death-ligand 1 (PD-L1). Blockage of ligation between PD-L1 and Programmed cell death protein 1 (PD1) induces local immune activation and prevent anergy and exhaustion of effectors T-cells.
Several studies have documented an increase in peripheral antitumor immunity following radiation. This effect is evidently too weak to be clinically relevant, but has the potential to be boosted by immune modulation.
The underlying hypothesis of this study is that the effect of Immune Checkpoint inhibitor (Durvalumab with or without Tremelimumab) treatment can be enhanced by radiation in patients with advanced pancreatic carcinoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug
时间窗: Participants were assessed from the start of study treatment at Cycle 1 then after every cycle (1 cycle = 28 days) of protocol treatment until 30 days after they were taken off treatment, approximately 4.0 months.
Adverse Events (AEs) are reported by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 1=Mild, Grade 2= Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Fatal.
次要结局
- Plasma Pharmacokinetic (PK)(30 days after treatment)
- Percentage of Participants With 6-month Overall Survival(6 month)
- Overall Survival(From study entry to death or date of last contact, whichever occurs first, up to 2 years of follow-up)
- Tumor Response Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as Measured by Computed Tomography (CT) and Magnetic Resonance Imaging (MRI)(At screening then every 8 weeks until disease progression or patient is taken off the trial, whichever comes first, approximately 6 months.)
- Progression Free Survival (PFS)(From study entry to disease progression, death or date of last contact, whichever occurs first, an average of 6 months)
- Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)(Date treatment consent signed to date off study, approximately 18 months and 4 days for Cohort 1/Dose Level A1, 23 months and 29 days for Cohort 2/Dose Level A2, 32 months and 19 days for Cohort C/Dose Level C1, and 44 months and 18 days for Cohort C/Dose)
研究者
Tim Greten, M.D.
Principal Investigator
National Cancer Institute (NCI)