Liver Only Metastasis From KRAS Exon 2 Wild Type (Under Protocol 1.0-1.2 Edition) and RAS Wild Type (Under Protocol 2.0 Edition) Colorectal Cancer
Conditions
Keywords
Bevacizumab, Cetuximab, KRAS wild type colorectal cancer, RAS wild type colorectal cancer, liver metastasis
Brief summary
The purpose of this study is to evaluate efficacy and safety of mFOLFOX6+bevacizumab and mFOLFOX6+cetuximab for liver only metastasis from KRAS Exon 2 wild type (under protocol 1.0-1.2 edition) and RAS wild type (under protocol 2.0 edition) colorectal cancer.
Detailed description
Description: The purpose of this study is to evaluate efficacy and safety of mFOLFOX6+bevacizumab and mFOLFOX6+cetuximab for liver only metastasis from KRAS Exon 2 wild type (under protocol 1.0-1.2 edition) and RAS wild type (under protocol 2.0 edition) colorectal cancer.
Interventions
DRUGl-LV
200 mg/m2 intravenously administered over 120 minutes on day 1 of a 2-week cycle. Liver resection if resectable after 8 cycles or continue until progression of disease.
DRUGBevacizumab
5 mg/kg intravenously administered over 90 minutes (can be reduced to 30 minutes at the minimum) on day 1 of a 2-week cycle. Liver resection if resectable after 8 cycles or continue until progression of disease.
DRUGCetuximab
250 mg/m2 intravenously administered over 60 minutes (400 mg/m2 over 120 minutes as the initial dose) on day 1 and day 8 of a 2-week cycle. Liver resection if resectable after 8 cycles or continue until progression of disease.
DRUGL-OHP
85 mg/m2 intravenously administered over 120 minutes on day 1 of a 2-week cycle. Liver resection if resectable after 8 cycles or continue until progression of disease.
DRUG5-FU
400 mg/m2 intravenous bolus on day 1 of a 2-week cycle. Liver resection if resectable after 8 cycles or continue until progression of disease.
Sponsors
EPS Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Histopathologically confirmed colorectal cancer (adenocarcinoma) excluding vermiform appendix cancer and proctos cancer. 2. RAS wild type 3. Synchronous\* or metachronous liver limited meitastasis with no extrahepatic desiease * shychronous liver limited metastasis with primary lesion less than two thirds of the circumference * patients with primary lesion more than two thirds of the circumference can be enrolled after primary resection 4. Patients who has one or more lesion(s) of diameter 1 cm or larger (RECEST v1.1) be able to assess continuously on the basis of the protocol by contrast enhanced CT or contrast enhanced MRI of the liver: (1)Liver metastases 5 or more (2)Liver metastases with 5 cm or larger in greatest dimension (3)Unresectable considering remaining hepatic function (4)Invasion into all hepatic veins or inferior vena cava (5)Invasion into both right and left hepatic arteries or portal veins 5.No prior chemotherapy for colorectal cancer including hepatic arterial infusion. Excluding postoperative and preoperative chemoradiotherapy except for rectal cancer with synchronous liver metastases. Patients received postoperative chemotherapy containing oxaliplatin have to be enrolled after 24 weeks from the last oxaliplatin administration. 6.No previous treatment including ablation therapy, cryotherapy and chemotherapy for metastases 7.Age at enrollment is \>=20 and =\<80 years 8.The Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 9.Life expectancy from the day of enrollment is 3 months or longer 10.Major organ functions less than 14 days prior to entry meet the following criteria. 1. Neu \>= 1500/mm3 2. Pt \>= 10.0x10\^4/mm3 3. Hb \>= 9.0 g/dL 4. T-bil =\< 2.0 mg/dL 5. AST and ALT =\< 200 IU/L 6. sCr =\< 1.20 mg/dL 7. INR \< 1.5 8. Proteinuria =\< 2+ 11.Written informed consent
Exclusion criteria
1. Previously experienced severe allergic reaction to drugs 2. Receiving anti-platelet drugs (aspirin \>= 325 mg/day) or NSAIDs 3. Receiving chronic systemic corticosteroid treatment 4. Surgery/ biopsy with skin incision or traumatic injury with suture less than 14 days prior to entry. Excluding, suture for implanted venous reservoirs with catherter is allowed. 5. Severe postoperative complications (e.g. postoperative infection, anastomic dehiscence or paralytic ileus) 6. Diagnosed as hereditary colorectal cancer 7. Active other malignancies 8. Cerebrovascular disease or symptoms less than 1 year prior to entry 9. Pleural effusion, ascites or cardiac effusion requiring drainage 10. Hemorrhage/bleeding, paralytic ileus, obstruction or ulceration of gastrointestinal tract 11. Perforation of gastrointestinal tract less than 1 year prior to entry 12. Presence of active infection 13. HBs antigen or HCV antibody positive 14. Uncontrolled comorbidity including hypertension, diabetes, arrhythmia, or other diseases (such as cardiac disorder, interstitial pneumonia or renal disorder) 15. Presence of \>= grade 2 diarrhea 16. Presence of \>= grade 1 peripheral neuropathy 17. Pregnant or lactating women. Women and men with childbearing potential unwilling to use effective means of contraception 18. Psychosis or psychiatric symptoms who are not able to comply with the protocol 19. Any other medical conditions disable to comply with the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival | assessed every 8 weeks, up to 4 years | assessed by Independent Review Committee |
Secondary
| Measure | Time frame |
|---|---|
| Response rate | assessed every 8 weeks, up to 4 years |
Other
| Measure | Time frame | Description |
|---|---|---|
| R0 liver resection rate | assessed every 8 weeks, up to 4 years | pathologically confirmed R0 liver resection rate |
| Progression-free survival | assessed every 8 weeks, up to 4 years | assessed by investigators |
| Time to treatment-failure | assessed every 2 weeks, up to 4 years | — |
| Tumor shrinkage rate at 8 week | assessed at 8 week, up to 8 weeks | — |
| Quality of life | assessed every 16 weeks, up to 1 year | — |
| Incidence of adverse events | assessed every 2 weeks, up to 4 years | — |
| Progression-free survival among the RAS wild type subpopulation | assessed every 8 weeks, up to 4 years | All the assessment is repeated for a maximum of 4 years. |
| Overall survival | assessed every 2 weeks, up to 4 years | — |
| Liver resection rate | assessed every 8 weeks, up to 4 years | — |
Countries
Japan
Outcome results
None listed