Colorectal Neoplasms, Digestive System Neoplasms, Gastrointestinal Neoplasms, Intestinal Neoplasms, Neoplasm Metastasis
Conditions
Keywords
FOLFIRI, CPT-11, Bevacizumab, 2nd-line metastatic colorectal cancer
Brief summary
The primary purpose of this study is to determine the non-inferiority of overall survival FOLFIRI with or without Bevacizumab compared with Irinotecan (CPT-11) with or without Bevacizumab as Second-line therapy in Patient with Metastatic Colorectal Cancer.
Detailed description
Primary endpoint: Progression-free survival (PFS)； Secondary endpoints: Overall survival (OS), Time to treatment failure (TTF), Overall response rate (ORR), Disease Control Rate (DCR), Safety.
Interventions
BIOLOGICALBevacizumab
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.
DRUGCPT-11
180 mg/m2 intravenously administered over 90 minutes on day 1 of a 2-week cycle
DRUG5-FU Bolus
400 mg/m2 intravenous bolus on day 1 of a 2-week cycle.
DRUG5-FU Infusion
2400 mg/m2 continuous infusion over 46 hours on day 1 and 2 of a 2-week cycle.
DRUGl-LV (dl-LV)
200 (dl-LV: 400) mg/m2 intravenously administered over 120 minutes on day 1 of a 2-week cycle.
Sponsors
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically-confirmed inoperable colorectal adenocarcinoma excluding vermiform appendix cancer and anal canal cancer. 2. Age ≥18 years at the time of informed consent 3. ECOG performance status (PS) of 0-2 4. Written informed consent prior to study-specific screening procedures 5. Life expectancy of at least 90 days 6. Withdrawal from first-line chemotherapy (regardless of containing molecular-targeted drugs) for metastatic colorectal cancer due to intolerable toxicity or progressive disease, or relapse within 180 days after the last dose of adjuvant chemotherapy. 7. Adequate organ function according to following laboratory values obtained within 14 days before enrolment (excluding patients who received blood transfusions or hematopoietic growth factors within 14 days before the laboratory test) Neutrophil count: ≥1500/mm3 Platelet count: ≥10.0 x 104/mm3 Hemoglobin: ≥9.0 g/dL Total bilirubin: ≤1.5 mg/dL AST, ALT: ≤100 IU/L (≤200 IU/I if liver metastases present) Serum creatinine: ≤1.5 mg/dL
Exclusion criteria
1. History of other malignancy with a disease-free interval \<5 years (other than curatively treated cutaneous basal cell carcinoma, curatively treated carcinoma in situ of the cervix, and gastroenterological cancer confirmed to be cured by endoscopic mucosal resection) 2. With massive pleural effusion or ascites requiring intervention 3. Radiological evidence of brain tumor or brain metastases 4. Active infection including hepatitis 5. Any of the following complication: i) Gastrointestinal bleeding or gastrointestinal obstruction (including paralytic ileus) ii) Symptomatic heart disease (including unstable angina, myocardial infarction, and heart failure) iii) Interstitial pneumonia or pulmonary fibrosis iv) Uncontrolled diabetes mellitus v) Uncontrolled diarrhea (that interferes with daily activities despite adequate therapy) 6. Any of the following medical history: Myocardial infarction: History of one episode within one year before enrollment or two or more lifetime episodes i) Serious hypersensitivity to any of the study drugs ii) History of adverse reaction to fluoropyrimidines suggesting dihydropyrimidine dehydrogenase (DPD) deficiency 7. Previous treatment with irinotecan hydrochloride 8. Current treatment with atazanavir sulfate 9. Previous treatment with tegafur, gimeracil, and oteracil potassium within seven days before enrollment 10. Pregnant or lactating females, and males and females unwilling to use contraception 11. Requires continuous treatment with systemic steroids 12. Psychiatric disability that would preclude study compliance 13. Otherwise determined by the investigator to be unsuitable for participation in the study 14. Concurrent gastrointestinal perforation or history of gastrointestinal perforation with 1 year before enrollment 15. History of pulmonary hemorrhage/hemoptysis ≥ Grade 2 (defined as bright red blood of at least 2.5mL) within 1 month prior to enrollment. 16. History of laparotomy, thoracotomy, or intestinal resection within 28 days before enrollment 17. Unhealed wound (except suture wounds from implantation of a central venous port), gastrointestinal ulcer, or traumatic fracture 18. Current or recent (within 1 year) thromboembolism or cerebrovascular disease 19. Currently receiving or requires anticoagulation therapy (\> 325 mg/day of aspirin) 20. Bleeding diathesis, coagulopathy, or coagulation factor abnormality (INR ≥1.5 within 14 days before enrollment) 21. Uncontrolled hypertension 22. Urine dipstick for proteinuria \>+2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | Assessed until 1.5 years after the last patient enrolment | Time from the date of enrollment to the earlier of the date of confirmed progression or death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | Assessed until 1.5 years after the last patient enrolment | Time from the date of enrollment to death from any cause |
| Time to treatment failure (TTF) | Assessed until 1.5 years after the last patient enrolment | Time from the date of enrollment to the earlier of the date of confirmed progression, death from any cause, or discontinuation of protocol treatment. |
| Overall Response Rate (ORR) | Assessed at 6, 12 week and thereafter every 8 weeks, from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks | Proportion of eligible patients with measurable lesions with a best overall response of CR or PR assessed by the attending physician. |
| Disease Control Rate (DCR) | Assessed at 6, 12 week and thereafter every 8 weeks, from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks | Proportion of best overall response of CR, PR, or SD assessed by the attending physician. |
| Incidence of Adverse Events (Adverse Reactions) | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks | The incidence of worst-grade adverse events (toxicities) on study as graded by NCI-CTCAE v 4.0 will be determined by treatment arm in all treated patients for the following events. |
Countries
China
Contacts
CONTACTRuihua Xu, MD, PhD
Outcome results
None listed