Phase 2b, DB, Randomized Study Evaluating Efficacy & Safety of Sorafenib Compared With Placebo When Administered in Combination With Modified FOLFOX6 for the Treatment of Metastatic CRC Subjects Previously Untreated for Stage IV Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 198
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
To determine if sorafenib when added to chemotherapy will slow disease progression more than chemotherapy alone in patients previously untreated for metastatic colorectal cancer.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 confirmation of adenocarcinoma of the colon or rectum
- •Tumor tissue sample available for KRAS and BRAF assessment
- •Measurable metastatic Stage IV disease including at least one measurable lesion that has not previously been radiated
- •No prior chemotherapy for metastatic CRC
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
- •Life expectancy of at least 12 weeks
- •Adequate bone marrow, liver, and renal function; adequate clotting parameters
排除标准
- •Prior treatment with sorafenib
- •Clinical or radiographic evidence of brain metastasis
- •Major surgery, surgical biopsy, or significant traumatic injury within 28 days of randomization; evidence or history of bleeding diathesis or coagulopathy
- •Red blood cell (RBC), white blood cell (WBC), or platelet transfusions and/or growth factor use within 28 days before randomization
- •Adjuvant therapy for CRC (Stage I, II, or III) completed within 12 months before randomization
- •Serious, non-healing wound, ulcer, or bone fracture; Grade 3 or 4 hemorrhage within 28 days before randomization
- •Use of anticoagulation therapy (low dose anticoagulation therapy to mitigate risk of thrombosis due to placement of a semi-permanent central venous port for administration of chemotherapy is allowed. The use of coumadin and related compounds is excluded.)
- •Uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic pressure > 100 mmHg on repeated measurement) despite optimal medical management
- •Thrombolic, embolic, venous, or arterial events (eg, cerebrovascular accident, including transient ischemic attacks) within 6 months before randomization
- •Active cardiac disease including:
- •Congestive heart failure
- •Unstable angina or myocardial infarction within the 6 months before randomization
- •Cardiac ventricular arrhythmias requiring antiarrhythmic treatment
- •Peripheral neuropathy > Grade 1 (CTCAE)
- •Known HIV infection or chronic hepatitis B or C infection
- •Any active infection >/= Grade 2 (CTCAE)
- •Any medical, psychological, or social condition that may interfere with the subject's participation in the study or evaluation of the study results
- •Use of any investigational drug within 28 days or 5 half-lives of that drug, whichever is longer, before randomization
- •Subjects with metastatic CRC who are currently candidates for surgery with curative intent
研究组 & 干预措施
Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6
Subjects will receive oral Sorafenib 400 mg twice daily (BID) continuously and intravenous (IV) mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease (PD)
干预措施: Sorafenib (Nexavar, BAY43-9006) + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin) (Drug)
Matching placebo + mFOLFOX6
Subjects will receive oral matching placebo 2 tablets BID continuously and IV mFOLFOX6 (5-FU 400 mg/m^2 bolus and 2400 mg/m^2 for 46-48 hrs; levo-leucovorin 200 mg/m^2; 85 mg/m^2 oxaliplatin) every 14 days until progressive disease
干预措施: Matching placebo + mFOLFOX6 (5-FU, levo-leucovorin, oxaliplatin) (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: From randomization of the first subject until 23 months later, assessed every 8 weeks.
Progression-free Survival (PFS) was defined as the time from date of randomization to disease progression or death due to any cause, whichever occurred first. Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation. Disease progression was defined as an increase of at least 20% in the sum of tumor lesions sizes.
次要结局
- Overall Survival (OS)(From randomization of the first subject until 33 months later.)
- Time to Progression (TTP)(From randomization of the first subject until 23 months later, assessed every 8 weeks.)
- Duration of Response(From randomization of the first subject until 23 months later, assessed every 8 weeks)
- Overall Response(From randomization of the first subject until 23 months later, assessed every 8 weeks.)