A Study of FOLFOXIRI Plus Cetuximab vs. FOLFOXIRI Plus Bevacizumab
Phase 2
- Conditions
- Colorectal Cancer
- Interventions
- Biological: bevacizumabBiological: cetuximab
- Registration Number
- NCT02515734
- Lead Sponsor
- Japan Clinical Cancer Research Organization
- Brief Summary
This study is to verify the advantage of FOLFOXIRI plus cetuximab over FOLFOXIRI plus bevacizumab as the first-line therapy in metastatic colorectal cancer patients with RAS wild-type tumors.
- Detailed Description
This study is to verify the advantage of FOLFOXIRI plus cetuximab over FOLFOXIRI plus bevacizumab as the first-line therapy in metastatic colorectal cancer patients with RAS wild-type tumors. In this study the investigators employed deepness of response as a primary endpoint.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 360
Inclusion Criteria
-
Histologically confirmed colorectal cancer
-
RAS wild-type
-
Measurable lesion by RECIST (Ver.1.1)
-
No past history of chemotherapy in the case of unresectable primary lesion/distant metastasis/lymph node metastasis.In the case of recurrence, no treatment for the first recurrence lesion after operation
-
Eastern Cooperative Oncology Group (ECOG) Performance status 0-1.The case >=71 years is PS0.
-
Life expectancy of more than 6 months
-
Patients have enough organ function for study treatment within 14 days before enrollment;
- White blood cell (WBC)>=3,000/mm3, <12,000/mm3.
- Neu>=1,500/mm3.
- Platelet count (PLT) >=10.0x104/mm3.
- Hb>=9.0g/dL.
- Total Bilirubin<=1.5x Upper Limited Normal (ULN)
- aspartate aminotransferase (AST) <=2.5xULN.
- alanine aminotransferase (ALT) <=2.5xULN.
- Creatinine<=1.5xULN.
- Proteinuria<=1+.
- prothrombin time-international normalized ratio (PT-INR) <=1.5
-
Must be able to swallow tablets
-
Written informed consent
Exclusion Criteria
- Synchronous multiple malignancy or metachronous multiple malignancy within 5 years disease free interval
- Lynch syndrome
- Brain metastases
- Infectious disease
- Interstitial lung disease or pulmonary fibrosis
- Comorbidity or history of serious heart failure
- History of thromboembolic events
- Cerebrovascular disease
- History of hemoptysis/hematemesis
- Uncontrolled hypertension (systolic BP>180mmHg, or diastolic BP>100mmHg)
- Sensory alteration or paresthesia interfering with function
- Large quantity of pleural, abdominal or cardiac effusion
- Severe comorbidity (renal failure, liver failure, hypertension, etc)
- Prior radiotherapy for primary and metastases leision
- Men/women who are unwilling to avoid pregnancy
- Women who are pregnant or breastfeeding
- Women with a positive pregnancy test
- History of severe allergy
- HBsAg positive or active viral hepatitis
- Administration of blood products/ Granulocyte-Colony Stimulating Factor (G-CSF), and blood transfusion within 14 days
- Surgical procedure or such as skin-open biopsy, trauma surgery, or other more intensive surgery within 28 days
- Systematic administration of antiplatelet drug or non steroid anti-inflammatory drugs (NSAIDs)
- Diathesis of bleeding (history of hemoptysis, including cavitation and/or necrosis in lung metastasis confirmed by imaging), coagulopathy
- History of gastrointestinal perforation within 1 year
- Unhealed traumatic bone fracture
- Uncontrolled diarrhea
- History of organ recipient
- Prior cetuximab/bevacizumab/Irinotecan/Oxaliplatin treatment (Adjuvant therapy by Oxaliplatin is excluded)
- Administration of atazanavir sulfate
- Jaundice
- Ileus or bowel obstruction
- Clinical diagnosis of Alzheimer's Disease
- Insulin dependent diabetes
- Thyroid disease
- Any other cases who are regarded as inadequate for study enrollment by investigators
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description FOLFOXIRI+Bmab bevacizumab Patients in the FOLFOXIRI + Bmab group receive until 12 cycles of FOLFOXIRI plus bevacizumab, consisting of a 30-minute infusion of bevacizumab at a dose of 5 mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and bevacizumab every 14 days until disease progression. FOLFOXIRI+Cmab cetuximab Patients in the experimental group received until 12 cycles of FOLFOXIRI plus cetuximab, consisting of a 30-minute infusion of cetuximab first time at a dose of 400 mg per kilogram, after the second time at a dose of 250mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and cetuximab every 14 days until disease progression. FOLFOXIRI+Bmab fluorouracil Patients in the FOLFOXIRI + Bmab group receive until 12 cycles of FOLFOXIRI plus bevacizumab, consisting of a 30-minute infusion of bevacizumab at a dose of 5 mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and bevacizumab every 14 days until disease progression. FOLFOXIRI+Bmab Leucovorin Patients in the FOLFOXIRI + Bmab group receive until 12 cycles of FOLFOXIRI plus bevacizumab, consisting of a 30-minute infusion of bevacizumab at a dose of 5 mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and bevacizumab every 14 days until disease progression. FOLFOXIRI+Bmab irinotecan Patients in the FOLFOXIRI + Bmab group receive until 12 cycles of FOLFOXIRI plus bevacizumab, consisting of a 30-minute infusion of bevacizumab at a dose of 5 mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and bevacizumab every 14 days until disease progression. FOLFOXIRI+Bmab oxaliplatin Patients in the FOLFOXIRI + Bmab group receive until 12 cycles of FOLFOXIRI plus bevacizumab, consisting of a 30-minute infusion of bevacizumab at a dose of 5 mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and bevacizumab every 14 days until disease progression. FOLFOXIRI+Cmab fluorouracil Patients in the experimental group received until 12 cycles of FOLFOXIRI plus cetuximab, consisting of a 30-minute infusion of cetuximab first time at a dose of 400 mg per kilogram, after the second time at a dose of 250mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and cetuximab every 14 days until disease progression. FOLFOXIRI+Cmab Leucovorin Patients in the experimental group received until 12 cycles of FOLFOXIRI plus cetuximab, consisting of a 30-minute infusion of cetuximab first time at a dose of 400 mg per kilogram, after the second time at a dose of 250mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and cetuximab every 14 days until disease progression. FOLFOXIRI+Cmab irinotecan Patients in the experimental group received until 12 cycles of FOLFOXIRI plus cetuximab, consisting of a 30-minute infusion of cetuximab first time at a dose of 400 mg per kilogram, after the second time at a dose of 250mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and cetuximab every 14 days until disease progression. FOLFOXIRI+Cmab oxaliplatin Patients in the experimental group received until 12 cycles of FOLFOXIRI plus cetuximab, consisting of a 30-minute infusion of cetuximab first time at a dose of 400 mg per kilogram, after the second time at a dose of 250mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and cetuximab every 14 days until disease progression.
- Primary Outcome Measures
Name Time Method Best deepness of response up to 2 years The maximum tumor shrinkage rates by Response Evaluation Criteria in Solid Tumors (RECIST) throughout the treatments
- Secondary Outcome Measures
Name Time Method Overall survival up to 2 years Deepness of response at 4 months The tumor shrinkage rates by RECIST at 4 months
Early tumor shrinkage at 8 weeks The rates of tumor shrinkage by RECIST at 8 weeks
Response rate up to 2 years Progression free survival up to 2 years Number of adverse events up to 2 years Rate of curatively resected metastatic lesion up to 2 years