A Phase III Trial of Modified FOLFOX6 Versus CAPOX, With Bevacizumab (NSC-704865) or Placebo, as First-Line Therapy in Patients With Previously Untreated Advanced Colorectal Cancer
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 2,200
- 试验地点
- 1
- 主要终点
- Overall survival in patients with colorectal cancer treated with fluorouracil/leucovorin calcium and oxaliplatin with and without becavizumab versus those treated with capecitabine and oxaliplatin with our without bevacizumab
研究概览
简要总结
Drugs used in chemotherapy, such as oxaliplatin, leucovorin, fluorouracil, and capecitabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. Combining chemotherapy with monoclonal antibody therapy may kill more tumor cells. It is not yet known which combination chemotherapy regimen with bevacizumab works better in treating colorectal cancer. This randomized phase III trial is studying giving two different combination chemotherapy regimens together with bevacizumab and comparing how well they work in treating patients with locally advanced, metastatic, or recurrent colorectal cancer
详细描述
OBJECTIVES:
I. Compare overall survival in patients with locally advanced, metastatic, or recurrent colorectal cancer treated with fluorouracil, leucovorin calcium, oxaliplatin, and bevacizumab vs capecitabine, oxaliplatin, and bevacizumab.
II. Compare progression-free survival and time to treatment failure in patients treated with these regimens.
III. Compare the response of patients with measurable disease treated with these regimens.
IV.Compare toxicity rates of these regimens in these patients. V. Compare patient-reported functional status and convenience of therapy in patients treated with these regimens.
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
- •Histologically or cytologically confirmed locally advanced, recurrent, or metastatic colorectal adenocarcinoma
- •Not curable by surgery or amenable to radiotherapy with curative intent
- •Previously resected colorectal cancer with new evidence of metastasis does not require separate histologic or cytologic confirmation unless one of the following is true:
- •More than 5 years has elapsed between primary surgery and development of metastatic disease
- •Primary tumor was T1-T2, N0, M0
- •Site of primary lesion must be or have been in the large bowel as determined by endoscopy, radiology, or surgery
- •Measurable or evaluable disease
- •No known brain or leptomeningeal disease
- •Performance status - Zubrod 0-2
- •No history of hemorrhagic or thrombotic disorders
- •Absolute neutrophil count greater than 1,500/mm^3
- •Platelet count greater than 100,000/mm^3
- •Bilirubin no greater than 2.0 times upper limit of normal (ULN)
- •SGOT no greater than 2.5 times ULN (5 times ULN for patients with liver involvement)
- •Alkaline phosphatase no greater than 2.5 times ULN (5 times ULN for patients with liver involvement or 10 times ULN for patients with bone involvement)
- •INR no greater than 1.5
- •PTT no greater than ULN
- •Creatinine no greater than 1.5 times ULN
- •Creatinine clearance at least 50 mL/min
- •Proteinuria less than 1+*
- •Protein less than 500mg/24 hours*
- •No uncontrolled hypertension
- •Hypertension must be well-controlled (i.e., less than 160/90) and on a stable regimen of antihypertensive therapy
- •No unstable angina
- •No symptomatic congestive heart failure
- •No myocardial infarction within the past 6 months
- •No serious uncontrolled cardiac arrhythmia
- •No New York Heart Association class III or IV heart disease
- •No symptomatic pulmonary fibrosis
- •Not pregnant or nursing
- •Fertile patients must use effective contraception
- •No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission
- •No active or uncontrolled severe infection
- •No contraindication to oral medications (e.g., severe dysphagia)
- •G-tubes or J-tubes allowed
- •No peripheral neuropathy greater than grade 1
- •No serious non-healing wound, ulcer, or bone fracture
- •No significant traumatic injury within the past 28 days
- •No other severe acute or chronic medical condition or laboratory abnormality that would preclude study participation
- •No psychiatric condition that would preclude study participation
- •No prior bevacizumab
- •No prior oxaliplatin
- •No prior chemotherapy for advanced colorectal cancer
- •Prior adjuvant therapy for resected stage II-III disease allowed provided at least 12 months have elapsed between completion of therapy and diagnosis of recurrent disease
- •At least 28 days since prior radiotherapy and recovered
- •See Disease Characteristics
- •More than 28 days since prior major surgical procedure or open biopsy
- •More than 7 days since prior fine needle aspiration or core biopsy
- •No concurrent major surgery
- •More than 10 days since prior full-dose aspirin (325 mg)
- 另有 8 项未显示
排除标准
- 未提供
研究组 & 干预措施
Arm I (oxaliplatin, leucovorin calcium, fluorouracil)
Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46-48 hours beginning on day 1. Patients are further randomized to receive bevacizumab or placebo* IV over 30-90 minutes on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. NOTE: *As of 11/15/04, placebo is no longer part of treatment plan; all patients receive bevacizumab.
干预措施: oxaliplatin (Drug)
Arm I (oxaliplatin, leucovorin calcium, fluorouracil)
Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46-48 hours beginning on day 1. Patients are further randomized to receive bevacizumab or placebo* IV over 30-90 minutes on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. NOTE: *As of 11/15/04, placebo is no longer part of treatment plan; all patients receive bevacizumab.
干预措施: leucovorin calcium (Drug)
Arm I (oxaliplatin, leucovorin calcium, fluorouracil)
Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46-48 hours beginning on day 1. Patients are further randomized to receive bevacizumab or placebo* IV over 30-90 minutes on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. NOTE: *As of 11/15/04, placebo is no longer part of treatment plan; all patients receive bevacizumab.
干预措施: bevacizumab (Biological)
Arm I (oxaliplatin, leucovorin calcium, fluorouracil)
Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46-48 hours beginning on day 1. Patients are further randomized to receive bevacizumab or placebo* IV over 30-90 minutes on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. NOTE: *As of 11/15/04, placebo is no longer part of treatment plan; all patients receive bevacizumab.
干预措施: fluorouracil (Drug)
Arm I (oxaliplatin, leucovorin calcium, fluorouracil)
Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46-48 hours beginning on day 1. Patients are further randomized to receive bevacizumab or placebo* IV over 30-90 minutes on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. NOTE: *As of 11/15/04, placebo is no longer part of treatment plan; all patients receive bevacizumab.
干预措施: laboratory biomarker analysis (Other)
Arm II (oxaliplatin, capecitabine)
Patients receive oxaliplatin IV over 2 hours on day 1and oral capecitabine on days 1-15. Patients are further randomized to receive bevacizumab or placebo* as in arm I. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity NOTE: *As of 11/15/04, placebo is no longer part of treatment plan; all patients receive bevacizumab.
干预措施: oxaliplatin (Drug)
Arm II (oxaliplatin, capecitabine)
Patients receive oxaliplatin IV over 2 hours on day 1and oral capecitabine on days 1-15. Patients are further randomized to receive bevacizumab or placebo* as in arm I. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity NOTE: *As of 11/15/04, placebo is no longer part of treatment plan; all patients receive bevacizumab.
干预措施: capecitabine (Drug)
Arm II (oxaliplatin, capecitabine)
Patients receive oxaliplatin IV over 2 hours on day 1and oral capecitabine on days 1-15. Patients are further randomized to receive bevacizumab or placebo* as in arm I. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity NOTE: *As of 11/15/04, placebo is no longer part of treatment plan; all patients receive bevacizumab.
干预措施: bevacizumab (Biological)
Arm II (oxaliplatin, capecitabine)
Patients receive oxaliplatin IV over 2 hours on day 1and oral capecitabine on days 1-15. Patients are further randomized to receive bevacizumab or placebo* as in arm I. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity NOTE: *As of 11/15/04, placebo is no longer part of treatment plan; all patients receive bevacizumab.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Overall survival in patients with colorectal cancer treated with fluorouracil/leucovorin calcium and oxaliplatin with and without becavizumab versus those treated with capecitabine and oxaliplatin with our without bevacizumab
时间窗: Up to 6 years
Will be analyzed primarily by the stratified Cox model.
次要结局
- Time to treatment failure(Up to 6 years)
- Progression-free survival(Up to 6 years)
- Response (among patients with measurable disease)(Up to 6 years)
- Treatment toxicities graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE 3.0)(Up to the time of progression)
- Change in FACT-C TOI(Baseline to 25 weeks)
- Change in Chemotherapy Convenience and Satisfaction Questionnaire scores(Baseline to 25 weeks)
- Whether gene expression variables are predictive of survival and progression-free survival(Up to 6 years)