Measurable advanced colorectal cancer with RAS wild-type ( KRAS exon 2,3,4
Conditions
Interventions
FOLFOXIRI+Bevacizumab (until 12 courses) 5-FU+Levofolinate+Bevacizumab (after 13 courses) Bevacizumab 5mg/kg/bi-weekly Irinotecan 150mg/m2/bi-weekly Oxaliplatin 85mg/m2/bi-weekly Levofolinate 2
Sponsors
Japan Clinical Cancer Reseach Organization (JACCRO)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: (1) Histologically confirmed colorectal cancer. (2) RAS wild-type. (3) Measurable leision by RECIST.(Ver.1.1) (4) 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 leision after operation. (5) Age; more than 20 years old. (6) ECOG Performance status 0-1.The case >=71 years is PS0. (7) Life expectancy of more than 6 months. (8) Patiens have enough organ function for study treatment within 14 days before enrollment; 1) WBC>=3,000/mm3, <12,000/mm3. 2) Neu>=1,500/mm3. 3) PLT>=10.0x104/mm3. 4) Hb>=9.0g/dL. 5) Total Bilirubin<=1.5xULN. 6) AST<=2.5xULN. 7) ALT<=2.5xULN. 8) Creatinine<=1.5xULN. 9) Proteinuria<=1+. 10) PT-INR<=1.5. (9) Written informed consent.
Exclusion criteria
Exclusion criteria: (1) Synchronous multiple malignancy or metachronous multiple malignancy within 5 years disease free interval. (2) Suspicious of Lynch syndrome (3) Brain metastases. (4) Infectious disease. (5) Interstitial lung disease or pulmonary fibrosis. (6) Comorbidity or history of serious heart failure. (7) History of thromboembolic events. (8) Cerebrovascular disease. (9) History of hemoptysis/hematemesis. (10) Uncontrolled hypertension.(systolic BP>180mmHg, or diastolic BP>100mmHg) (11) Sensory alteration or paresthesia interfering with function. (12) Large quantity of pleural, abdominal or cardiac effusion. (13) Severe comorbidity (renal failure, liver failure, hypertension, etc) (14) Prior radiotherapy for primary and metastases leision. (15) Men/women who are unwilling to avoid pregnancy. Women who are pregnant or breastfeeding. Women with a positive pregnancy test. (16) History of severe allergy. (17) HBsAg positive or active viral hepatitis. (18) Administration of blood products/ G-CSF, and blood transfusion within 14 days. (19) Surgical procedure or such as skin-open biopy, trauma surgery, or other more intensive surgeries within 28 days. (20) Systemaic administration of antiplatelet drug or NSAIDs. (21) Diathesis of bleeding (history of hemoptysis, including cavitation and/or necrosis in lung metastasis confirmed by imaging), coagulopathy. (22) History of gastrointestinal perforation within 1 year. (23) Unhealed traumatic bone fracture. (24) Uncontrolled diarrhea. (25) History of organ recipient . (26) Prior cetuximab/bevacizumab/Irinotecan/Oxaliplatin treatment.(Adjuvant therapy by Oxaliplatin is excluded) (27) Administration of atazanavir sulfate. (28) Jaundice. (29) Ileus or bowel obstruction. (30) Any other cases who are regarded as inadequate for study enrollment by investigators.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| DpR: Deepness of Response | — |
Secondary
| Measure | Time frame |
|---|---|
| ETS: Early Tumor shrinkage RR: Response Rate DpR: Deepness of Response (at 4 weeks) TTF: Time to Treatment Failure TTG: Time to Tumor Growth PFS: Progression-Free Survival OS: Overall Survival Correlation between tumor shrinkage(ETS, RR, DpR) and prognosis(PFS, OS) Correlation between TTG and OS Resection rate R0 resection rate Safety | — |
Countries
Japan
Contacts
Public ContactMasashi Fujii
Japan Clinical Cancer Reseach Organization (JACCRO) Research Office
Outcome results
None listed