A Phase 2 Randomized, Open-Label Study of RRx-001 vs Regorafenib in Subjects With Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 62
- 试验地点
- 5
- 主要终点
- Overall Survival
研究概览
简要总结
This two-stage study is designed to compare the safety and activity between RRx-001 against regorafenib followed by irinotecan-based therapies in a parallel comparative study.
Patients who are suffering from advanced or metastatic (meaning the disease has spread) colorectal cancer are invited to participate in this study. There will be two groups of patients (Randomized, open label study), one of these will receive RRx-001 and the other one will receive regorafenib. If patients qualify to participate in this study, they will be randomly assigned to the 'interventional arm' where patients will receive the experimental drug, RRx-001, or the 'control arm' where they will receive the current standard-of-care, Regorafenib. Patients have a 66% chance (2 out of 3) of receiving RRx-001 and a 33 % chance (1 out of 3) of receiving regorafenib.
On progression in the first part of the study, provided ECOG performance status is adequate, and if clinically appropriate i.e. there are no absolute or relative contraindications in the opinion of the Investigator, all subjects will enter the second part of the study and receive irinotecan plus bevacizumab.
Whether patients are given RRx-001 or regorafenib, they will also receive best supportive care, which includes treatments to help manage side effects and symptoms of cancer. This is an open label study, which means patients will know to which of these treatments, RRx-001 or regorafenib, they are assigned.
详细描述
Purpose This two-stage study is designed to compare the safety and activity between RRx-001 against regorafenib followed by irinotecan-based therapies in a parallel comparative study.
Patients who are suffering from advanced or metastatic (meaning the disease has spread) colorectal cancer are invited to participate in this study. There will be two groups of patients (Randomized, open label study), one of these will receive RRx-001 and the other one will receive regorafenib. Qualifying patients will be randomly assigned (like the flip of a coin) to the 'interventional arm' and receive the experimental drug, RRx-001, or the 'control arm' where they will receive the current standard-of-care, Regorafenib. Patients will have a 66% chance (2 out of 3) of receiving RRx-001 and a 33 % chance (1 out of 3) of receiving regorafenib.
On progression in the first part of the study, provided ECOG performance status is adequate, and if clinically appropriate i.e. there are no absolute or relative contraindications in the opinion of the Investigator, all subjects will enter the second part of the study receive irinotecan plus bevacizumab.
Whether patients are given RRx-001 or regorafenib, they will also receive best supportive care, which includes treatments to help manage side effects and symptoms of cancer. This is an open label study, which means patients will know to which of these treatments, RRx-001 or regorafenib, they are assigned.
Background Oxygen is vital to life, we need it to breathe, for example, but at the same time it gives rise to byproducts that are toxic called free radicals. Free radicals are defined as "oxidants". Similarly, substances that interact with and neutralize free radicals, thus preventing them from causing damage, are called "antioxidants". Examples of recognizable antioxidants are Vitamin E, Vitamin C and beta-carotene. Antioxidants are also known as "free radical scavengers." When free radicals are present in excess of antioxidants damage may occur.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Histological or cytological documentation of adenocarcinoma of the colon or rectum;
- •Subject must have received at least oxaliplatin-, and irinotecan-based regimens with bevacizumab and with, cetuximab or panitumumab if KRAS wildtype and are refractory to irinotecan;
- •Subject has measurable disease by radiographic techniques (computerized tomography [CT] or magnetic resonance imaging [MRI]);
- •Subjects with a history of brain metastasis are eligible for the study as long as they meet all the following criteria: their brain metastases have been treated, they have no evidence of progression or hemorrhage after treatment, have been off dexamethasone for 4 weeks prior to first study drug administration, and have no ongoing requirement for dexamethasone or anti-epileptic drugs;
- •Life expectancy of at least 12 weeks
- •Subject's Eastern Cooperative Group (ECOG) performance status is 0 or 1;
- •Adequate organ function
- •Fertile subjects must use effective contraception during the course of the study and for 30 days following withdrawal from the study;
排除标准
- •Clinically significant cardiovascular disease;
- •Unresolved toxicity higher attributed to any prior therapy/procedure excluding alopecia, hypothyroidism and oxaliplatin- induced neurotoxicity ≤ Grade 2 for at least 14 days;
- •Evidence or history of tendency or predisposition to active bleeding. Any hemorrhage or bleeding event of Grade 3 or higher within 4 weeks of start of study medication;
- •Symptoms or signs of active brain metastases;
- •History of an allergic reaction or intolerance to irinotecan
- •Hepatic encephalopathy
- •Cholangitis that required treatment or intervention within 4 weeks of study enrollment
- •Concurrent anticancer therapy or any cytotoxic therapy within 1 month prior to Day
- •Corticosteroid therapy is not allowed except on dosing days;
- •Subject has previously received regorafenib;
- •Clear contraindication for systemic corticosteroids (diabetes mellitus is not per se a clear contraindication);
- •Severe hypoalbuminemia (albumin < 3.0 g/dL);
- •Subjects who are pregnant or lactating or who are planning to become pregnant during the course of the study are excluded.
研究组 & 干预措施
RRx-001 followed by irinotecan
Once-weekly intravenous RRx-001 at a dose of 4 mg on Days 1, 8, 15, and 22 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab)
干预措施: RRx-001 (Drug)
RRx-001 followed by irinotecan
Once-weekly intravenous RRx-001 at a dose of 4 mg on Days 1, 8, 15, and 22 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab)
干预措施: Irinotecan (Drug)
Regorafenib followed by irinotecan
Regorafenib daily on Days 1- 21 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab)
干预措施: Regorafenib (Drug)
Regorafenib followed by irinotecan
Regorafenib daily on Days 1- 21 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab)
干预措施: Irinotecan (Drug)
结局指标
主要结局
Overall Survival
时间窗: From date of enrollment until death or censorship.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 47 months
次要结局
- Progression Free Survival(Baseline, every 6-8 weeks while on study.)
- Number of Adverse Events(Baseline through end of treatment (28 days after last dose of study drug). Approximately 24 weeks.)
- Objective Response Rate(Up to 2 years)
- Clinical Benefit Rate(Up to 2 years)