Phase I/Ib Study of Surgical Resection or Radiofrequency Ablation (RFA) of Metastatic Lesions in the Liver in Combination With Monoclonal Antibody to OX40 (MEDI6469) in Patients With Metastatic Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Safety (side-effects or complications related to the study drug)
研究概览
简要总结
This study will test the ability of an immune modulator, anti-OX40 (MEDI6469) to alter the immune cell environment within colorectal cancer metastases. The drug will be administered to patients before surgical treatment.
详细描述
There will be three distinct cohorts of patients which will vary the timing of the MEDI6469 dose, starting three weeks before surgery and decreasing the interval before surgery by one week with each cohort, as long as no dose-limiting toxicity attributable to the anti-OX40 are observed.
Immunohistochemistry will be used to measure the immune cells within primary and metastatic tumors when resected tissue is available, and surgically ablated tumors, giving each specimen an "immune score". The primary endpoint of the study will be the difference in immune scores of patients treated with anti-OX40 compared to historical controls (immune scores of untreated patients). Secondary endpoints will include both clinical (survival) and immunological data (specific measurements of immune cell populations based on flow cytometry and immunohistochemistry).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who will undergo staged liver resections are included in this study. In these cases, preoperative MEDI6469 will be given prior to the initial procedure.
- •Patients with small <3 cm tumors located >2 cm away from central bile ducts will be considered for either radiofrequency ablation or resection, the choice of which will be determined at the time of surgery.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Laboratory values during preoperative assessment within the protocol specified range
- •Ability to give informed consent and comply with the protocol. Patients with a history of psychiatric illness must be judged able to understand the investigational nature of the study and the risks associated with the therapy.
- •No active gastrointestinal bleeding.
- •No clinical or laboratory coagulopathy
- •Anticipated lifespan greater than 12 weeks
排除标准
- •Metastatic disease outside of the liver that is not considered surgically resectable or curable.
- •Active infection.
- •Active autoimmune disease including patients with Inflammatory Bowel Disease as determined by an autoimmune questionnaire.
- •Previous treatment with mouse monoclonal antibodies.
- •Need for chronic maintenance oral steroids.
- •Any medical or psychiatric condition that in the opinion of the PI would preclude compliance with study procedures.
- •Enrollment in a clinical trial in which a different investigational agent is administered within 4 weeks prior to the first dose of MEDI6469.
研究组 & 干预措施
21 Days
MEDI6469 0.4 mg/kg IV x 3 doses over 5-6 days starting 21 days prior to surgery
干预措施: MEDI6469 (Drug)
14 Days
MEDI6469 0.4 mg/kg IV x 3 doses over 5-6 days starting 14 days prior to surgery
干预措施: MEDI6469 (Drug)
7 Days
MEDI6469 0.4 mg/kg IV x 3 doses over 5-6 days starting 7 days prior to surgery
干预措施: MEDI6469 (Drug)
结局指标
主要结局
Safety (side-effects or complications related to the study drug)
时间窗: 48 Days
Patients are seen at least 7 times in clinic and have 3 physical exams and provide interim medical history four times to identify potential side-effects or complications related to the study drug.
Immune Score
时间窗: 27 Days
The number of CD8 effector T cells, CD4 regulatory T cells, the expression of activation markers OX40, CD38 and HLA-DR.
次要结局
未报告次要终点