Colorectal Cancer
Conditions
Keywords
FOLFOXIRI, Bmab, Cmab
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.
Interventions
DRUGfluorouracil
DRUGLeucovorin
DRUGirinotecan
DRUGoxaliplatin
BIOLOGICALbevacizumab
BIOLOGICALcetuximab
Sponsors
Japan Clinical Cancer Research Organization
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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; 1. White blood cell (WBC)\>=3,000/mm3, \<12,000/mm3. 2. Neu\>=1,500/mm3. 3. Platelet count (PLT) \>=10.0x104/mm3. 4. Hb\>=9.0g/dL. 5. Total Bilirubin\<=1.5x Upper Limited Normal (ULN) 6. aspartate aminotransferase (AST) \<=2.5xULN. 7. alanine aminotransferase (ALT) \<=2.5xULN. 8. Creatinine\<=1.5xULN. 9. Proteinuria\<=1+. 10. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Early tumor shrinkage | at 8 weeks | The rates of tumor shrinkage by RECIST at 8 weeks |
| Response rate | up to 2 years | — |
| Deepness of response | at 4 months | The tumor shrinkage rates by RECIST at 4 months |
| Overall survival | up to 2 years | — |
| Progression free survival | up to 2 years | — |
| Rate of curatively resected metastatic lesion | up to 2 years | — |
| Number of adverse events | up to 2 years | — |
Contacts
Primary ContactMasashi Fujii, MD
Backup ContactSachika Koyama, Ms
Outcome results
None listed