A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of GS-6624 Combined With FOLFIRI as Second Line Treatment for Metastatic KRAS Mutant Colorectal Adenocarcinoma That Has Progressed Following a First Line Oxaliplatin- and Fluoropyrimidine-Containing Regimen
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 266
- 试验地点
- 103
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
The primary objective of this study is to compare the additive efficacy of SIM versus placebo in combination with leucovorin (folinic acid), irinotecan, and fluorouracil (FOLFIRI) as measured by improvement in progression-free survival (PFS) in participants with metastatic KRAS mutant colorectal adenocarcinoma who have progressed following a first-line oxaliplatin- and fluoropyrimidine-containing regimen.
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
- Double (Participant, Investigator)
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
- •Metastatic colorectal carcinoma with KRAS mutation
- •Received first line therapy and discontinued part or all of first line therapy
- •Estimated life expectancy > 3 months
- •Stage IV disease
- •Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
- •Adequate hepatic and hematologic function
- •No major operations within 4 weeks prior to treatment start
排除标准
- •More than 1 prior chemotherapy regimen for Stage 4 colorectal cancer
- •Experimental medical treatment within 30 days prior to study entry
- •Known or suspected cerebral metastases
- •History or presence of any form of cancer, other that colorectal cancer, within the 3 years prior to enrollment
- •Known dihydropyrimidine dehydrogenase-deficiency (special screening not required)
- •Subjects with angina pectoris, poorly controlled ventricular arrhythmias (does not include asymptomatic, occasional premature ventricular contractions), history of clinically significant coronary heart disease or cardiomyopathy, or electrocardiogram (ECG) abnormalities consistent with ischemia
- •Uncontrolled hypertension (seated systolic blood pressure > 180 mm Hg or diastolic blood pressure > 110 mm Hg) at screening
- •Clinically active liver disease, including active hepatitis (any etiology) or cirrhosis
- •Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, retinoid therapy, hormonal therapy) within 21 days prior to randomization
- •Prior irinotecan therapy for metastatic disease is not permitted
- •Systemic fungal, bacterial, viral, or other infection
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
FOLFIRI + SIM 700 mg (Part A)
Participants will receive SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
干预措施: Simtuzumab (Biological)
FOLFIRI + SIM 700 mg (Part A)
Participants will receive SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
干预措施: Leucovorin (Drug)
FOLFIRI + SIM 700 mg (Part A)
Participants will receive SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
干预措施: Irinotecan (Drug)
FOLFIRI + SIM 700 mg (Part A)
Participants will receive SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
干预措施: Fluorouracil (Drug)
FOLFIRI + SIM 200 mg (Part B)
Participants will receive SIM 200 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
干预措施: Simtuzumab (Biological)
FOLFIRI + SIM 200 mg (Part B)
Participants will receive SIM 200 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
干预措施: Leucovorin (Drug)
FOLFIRI + SIM 200 mg (Part B)
Participants will receive SIM 200 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
干预措施: Irinotecan (Drug)
FOLFIRI + SIM 200 mg (Part B)
Participants will receive SIM 200 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
干预措施: Fluorouracil (Drug)
FOLFIRI + SIM 700 mg (Part B)
Participants will receive SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
干预措施: Simtuzumab (Biological)
FOLFIRI + SIM 700 mg (Part B)
Participants will receive SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
干预措施: Leucovorin (Drug)
FOLFIRI + SIM 700 mg (Part B)
Participants will receive SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
干预措施: Irinotecan (Drug)
FOLFIRI + SIM 700 mg (Part B)
Participants will receive SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
干预措施: Fluorouracil (Drug)
FOLFIRI + Placebo (Part B)
Participants will receive placebo to match SIM via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
干预措施: Placebo to match SIM (Drug)
FOLFIRI + Placebo (Part B)
Participants will receive placebo to match SIM via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
干预措施: Leucovorin (Drug)
FOLFIRI + Placebo (Part B)
Participants will receive placebo to match SIM via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
干预措施: Irinotecan (Drug)
FOLFIRI + Placebo (Part B)
Participants will receive placebo to match SIM via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
干预措施: Fluorouracil (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Randomization up to 27 months
The PFS was defined as the time from the date of randomization to the earliest event time of: a) death regardless of cause, or b) first indication of disease progression. PFS was analyzed using Kaplan-Meier (KM) estimates.
次要结局
- Overall Survival (OS)(Randomization up to 33 months)
- Objective Response Rate (ORR)(Randomization up to 27 months)