A Phase I Study of Riluzole in Combination With mFOLFOX6/Bevacizumab in Patients With Metastatic Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Dose limiting toxicities (DLTs)
研究概览
简要总结
This phase I trial is to find out the best dose, possible benefits, and/or side effects of riluzole and how well it works in combination with standard of care mFOLFOX6 and bevacizumab in treating patients with colorectal cancer that has spread to other places in the body (metastatic). Riluzole is a well-tolerated oral medication that has demonstrated it may make chemotherapy work better. Chemotherapy drugs, such as oxaliplatin, leucovorin calcium and fluorouracil, work in different ways to stop the growth of [cancer/tumor] cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bevacizumab is an antibody that targets the blood vessel by blocking the activity of a protein called vascular endothelial growth factor alpha (VEGF-A). It helps to make the mFOLFOX6 more effective. Giving riluzole, mFOLFOX6, and bevacizumab may kill more tumor cells compared to mFOLFOX6 and bevacizumab alone in treating patients with colorectal cancer.
详细描述
PRIMARY OBJECTIVE:
I. Characterize the safety and toxicity of riluzole in combination with modified (m) leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX) 6/bevacizumab and determine the recommended phase II dose (RP2D) of riluzole in combination with mFOLFOX6/bevacizumab in patients with metastatic colorectal cancer.
SECONDARY OBJECTIVE:
I. Determine the pharmacokinetics of riluzole in patients with metastatic CRC.
EXPLORATORY OBJECTIVES:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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 with metastatic colorectal cancer, who are appropriate candidates to receive mFOLFOX6/bevacizumab. Patients who progressed on FOLFOX-based regimen are allowed
- •Willingness to undergo both pre-treatment and post-treatment tumor tissue biopsies (pre-treatment tumor tissue will be sent to pathology lab to confirm metastatic colorectal cancer as the standard of care)
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Age >= 18 years
- •Absolute neutrophil count >= (ANC) 1,500/ul
- •Platelets >= 100,000/ul
- •Hemoglobin >= 9 g/dl
- •Serum total bilirubin < 1.5 x ULN
- •Serum albumin >= 2.5 g/dl
- •If no liver involvement, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 1.5 x ULN. If liver involvement, AST and ALT =< 3.0 x ULN
- •Ability to understand and the willingness to sign a written informed consent document
- •A male subject of fathering potential must use an adequate method of contraception to avoid conception throughout the study (and for up to 12 weeks after the last dose of study drug) to minimize the risk of pregnancy. If the partner is pregnant or breastfeeding, the subject must use a condom
- •Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of study drug to minimize the risk of pregnancy. WOCBP must have a negative serum or urine pregnancy test within 72 hours before the start of the investigational product
排除标准
- •Patients who are receiving any other investigational agents
- •Patients with history of hepatitis B or C
- •Patients with severe renal impairment (CrCl < 30 mL/min)
- •Prior full field radiotherapy < 4 weeks or limited field radiotherapy < 2 weeks prior to first study drug administration. Patients with central nervous system (CNS) metastases may participate in this trial provided they are clinically stable. Patients who are < 1 month from radiation therapy must not be included
- •Patients with existing grade 2 peripheral neuropathy
- •Patients with a history of thrombotic or embolic events within the last six months such as a cerebrovascular accident (including transient ischemic attacks), pulmonary embolism or deep vein thrombosis
- •Cardiac conditions as follows:
- •Active coronary artery disease, unstable or newly diagnosed angina or myocardial infarction less than 6 months prior to first study drug administration
- •Class III-IV New York Heart Association (NYHA) congestive heart failure
- •Uncontrolled hypertension (Systolic blood pressure [BP] > 150 mmHg and diastolic BP > 90 mmHg for 24 hours) despite optimal medical management
- •Corrected QT (QTc) (Friderica) prolongation > 480 msec
- •Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, cardiac arrhythmia, active bleeding diatheses, and psychiatric illness/social situations that would limit compliance with study requirements
- •Major surgical procedure or significant traumatic injury less than 3 weeks or those who receive minor surgical procedures within 1 week from first dose of study drug administration
- •Known inability to swallow capsules
- •Inability to comply with study and/or follow-up procedures
- •Pregnant women are excluded from this study. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued
研究组 & 干预措施
Treatment (riluzole, mFOLFOX6, bevacizumab)
Patients receive riluzole PO BID on days 1-14. Patients also receive oxaliplatin via IVPB over 2 hours, leucovorin calcium IVPB over 2 hours, and bevacizumab IVPB over 30 minutes on day 1 and fluorouracil via IV push over 5 minutes and then IV continuously over 46 hours on days 1-2. Treatment repeats every 2 weeks for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Bevacizumab (Biological)
Treatment (riluzole, mFOLFOX6, bevacizumab)
Patients receive riluzole PO BID on days 1-14. Patients also receive oxaliplatin via IVPB over 2 hours, leucovorin calcium IVPB over 2 hours, and bevacizumab IVPB over 30 minutes on day 1 and fluorouracil via IV push over 5 minutes and then IV continuously over 46 hours on days 1-2. Treatment repeats every 2 weeks for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Fluorouracil (Drug)
Treatment (riluzole, mFOLFOX6, bevacizumab)
Patients receive riluzole PO BID on days 1-14. Patients also receive oxaliplatin via IVPB over 2 hours, leucovorin calcium IVPB over 2 hours, and bevacizumab IVPB over 30 minutes on day 1 and fluorouracil via IV push over 5 minutes and then IV continuously over 46 hours on days 1-2. Treatment repeats every 2 weeks for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Leucovorin Calcium (Drug)
Treatment (riluzole, mFOLFOX6, bevacizumab)
Patients receive riluzole PO BID on days 1-14. Patients also receive oxaliplatin via IVPB over 2 hours, leucovorin calcium IVPB over 2 hours, and bevacizumab IVPB over 30 minutes on day 1 and fluorouracil via IV push over 5 minutes and then IV continuously over 46 hours on days 1-2. Treatment repeats every 2 weeks for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Oxaliplatin (Drug)
Treatment (riluzole, mFOLFOX6, bevacizumab)
Patients receive riluzole PO BID on days 1-14. Patients also receive oxaliplatin via IVPB over 2 hours, leucovorin calcium IVPB over 2 hours, and bevacizumab IVPB over 30 minutes on day 1 and fluorouracil via IV push over 5 minutes and then IV continuously over 46 hours on days 1-2. Treatment repeats every 2 weeks for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Riluzole (Drug)
结局指标
主要结局
Dose limiting toxicities (DLTs)
时间窗: Up to 4 weeks (2 cycles of treatment) (1 cycle = 14 days)
Will be defined by treatment related grade \>= 4 adverse events or \>= grade 3 alanine aminotransferase or aspartate aminotransferase elevation during the DLT period using the Common Terminology Criteria for Adverse Events version 5.0.
次要结局
- Pharmacokinetic (PK) profile of riluzole (Cmax)(Day 1 on cycle 1 (each cycle is 14 days))
- Pharmacokinetic (PK) profile of riluzole (AUC)(Day 1 on cycle 1 (each cycle is 14 days))
研究者
Ning Jin
Principal Investigator
Ohio State University Comprehensive Cancer Center