An Open-label, Multicenter, Randomized Phase 2 Study Evaluating the Safety and Efficacy of 5 FU/FA and Oxaliplatin (Modified FOLFOX 6) in Combination With Ramucirumab or IMC-18F1 or Without Investigational Therapy as Second Line Therapy in Patients With Metastatic Colorectal Cancer Following Disease Progression on First Line Irinotecan-based Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 158
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
The purpose of this study is to determine if participants with metastatic colorectal cancer live longer without their cancer progressing when treated with standard chemotherapy, standard chemotherapy plus ramucirumab, or standard chemotherapy plus icrucumab.
详细描述
The purpose of this study is to evaluate the progression-free survival (PFS) in participants with metastatic colorectal cancer when treated with 1 of 3 modified FOLFOX-6 (folinic acid [FA] + fluorouracil [5-FU] + oxaliplatin [mFOLFOX-6])-based regimens, as second-line therapy.
During 2010, there has been an identified shortage of injectable folinic acid (FA) in the United States. Levo-folinic acid (LFA) will be allowed as a substitute for FA in the mFOLFOX-6 chemotherapy regimen in circumstances in which FA is not available, to facilitate continuity of participant care.
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
- •Disease progression on an irinotecan-based first-line chemotherapy regimen (ie FOLFIRI or CAPIRI [capecitabine + irinotecan], with or without bevacizumab)
- •Age ≥ 18 years
- •Life expectancy of ≥ 6 months
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1 at study entry
- •Agrees to adequate contraception during the study period and for 12 weeks after the last dose of study medication
- •Provided signed informed consent
排除标准
- •Has received prior oxaliplatin-based chemotherapy for locally advanced unresectable or metastatic Colorectal Cancer (CRC) (Prior oxaliplatin-based adjuvant chemotherapy is allowed if the last dose of oxaliplatin was administered > 12 months prior to randomization)
- •Has documented and/or symptomatic brain or leptomeningeal metastases
- •Has an ongoing or active infection, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorders
- •On chronic non-topical corticosteroid treatment. A participant discontinuing such treatment > 3 months prior to randomization is eligible
- •Has uncontrolled or poorly controlled hypertension on a standard regimen of antihypertensive therapy
- •Has a concurrent active malignancy. A participant with previous history of malignancy is eligible, provided that he/she has been disease free for > 3 years
- •If female, is pregnant (confirmed by serum beta human chorionic gonadotropin [βHCG] test) or lactating
- •Has received a prior autologous or allogeneic organ or tissue transplantation
- •Has undergone major surgery within 28 days prior to randomization
- •Has had a serious nonhealing wound, ulcer, or bone fracture within 28 days prior to randomization
- •Has an elective or planned major surgery to be performed during the course of the trial
- •Has a history of inflammatory bowel disease requiring pharmacological and/or surgical intervention in the 12 months prior to randomization
研究组 & 干预措施
mFOLFOX-6
mFOLFOX-6
干预措施: mFOLFOX-6 (Drug)
mFOLFOX-6 + Ramucirumab
mFOLFOX-6 + Ramucirumab
干预措施: Ramucirumab (Biological)
mFOLFOX-6 + Ramucirumab
mFOLFOX-6 + Ramucirumab
干预措施: mFOLFOX-6 (Drug)
mFOLFOX-6 + Icrucumab
mFOLFOX-6 + Icrucumab
干预措施: Icrucumab (Biological)
mFOLFOX-6 + Icrucumab
mFOLFOX-6 + Icrucumab
干预措施: mFOLFOX-6 (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Baseline until Disease Progression or Death from Any Cause (Up to 95 Weeks)
PFS is defined as the time from baseline until the date of disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1), or death from any cause, whichever was first. Participants who die without a reported prior progression will be considered to have progressed on the day of their death. Participants who did not progress, are lost to follow-up, or have missed two or more scheduled tumor assessments will be censored at the day of their last radiographic tumor assessment, if there are no post-baseline tumor measurements for a randomized and treated participant, the participant will be censored at the date of randomization. If death or progressive disease (PD) occurs after 2 or more missing radiographic visits, censoring will occur at the date of the last radiographic visit prior to the last visit.
次要结局
- Pharmacokinetics (PK): Maximum Concentration (Cmax) at Cycle 5(Cycle 5, 1 Hour Post End of Infusion)
- Pharmacokinetics (PK): Trough Serum Concentrations (Ctrough) at Cycle 5(Cycle 5, Prior to Infusion)
- Maximum Concentration (Cmax) at Day 8(Day 8 (cycles 1 and 5))
- Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])(Baseline until Disease Progression (Up to 95 Weeks))
- Duration of Response (DoR)(Criteria First Met for CR or PR until Disease Progression or Death from Any Cause (Up to 95 Weeks))
- Overall Survival (OS)(Baseline Until Death from Any Cause (Up to 163 Weeks))
- Maximum Concentration (Cmax) at Day 15(Day 15 (Cycles 1 and 5))
- Minimum Concentration (Cmin) at Day 1(Day 1 (cycles 1, 5, 9, and 13))
- Minimum Concentration (Cmin) at Day 4(Day 4 (cycles 1 and 5))
- Minimum Concentration (Cmin) at Day 8(Day 8 (cycles 1 and 5))
- Number of Participants With Serum Ramucirumab Antibody Assessment(31 Weeks)
- Minimum Concentration (Cmin) at Day 15(Day 15 (cycles 1 and 5))
- Serum Anti-Icrucumab Antibody Assessment(31 Weeks)
- Number of Participants With Adverse Events(Baseline up to 165 weeks)