Patients with advanced or recurrent colorectal cancer after failure to Irinotecan.
Conditions
Interventions
High-dose Bevacizumab + sLV5FU2 Bevacizumab 10mg/kg (d.i.v) L-OHP 85 mg/m2 (d.i.v) l-LV 200mg/m2 (d.i.v) 5-FU 400mg/m2 (b.i.v) 5-FU 2400mg/m2 (c.i.v) Every 2weeks
Sponsors
Third Department of Surgery,Tokyo Medical University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Histological confirmation of colorectal cancer. 2.Patients with disease progression (according to RECIST criteria),and previously treated with Bevacizumab and Irinotecan-based chemotherapy as first- line therapy. 3.Bevacizumab was continued until the disease progression except for withdrawal from Irinotecan and Bevacizumb as first-line chemotherapy due to progressive disease. (If irinotecan is discontinued due to adverse events or withdrawal, the continuation Strategy of fluoropyrimidine combination with Bevacizumab is Considered) 4.Diagnosis of progression of disease less than 2 months after last Bevacizumab administration. 5.No previous treatment with EGFR antibody therapy contained regimen. 6.Unresectable primary tumor or with one or more unresectable metastatic tumor. 7.No previous metastasectomy 8.20 years old or more when received informed consent. 9.Eastern Cooperative Oncology Group (ECOG) performance status (PS):0 - 2. 10.With estimative lesion observed in imaging or intraoperation within 28 days before registration. (measurable lesions in RECIST criteria (ver.1.1)is dispensable) 11.Withdrawal from first-line chemotherapy due to toxicity or progressive disease 12.Patients with metastatic colorectal cancer who had previously received first- line therapy with an Irinotecan-based regimen. 13.No previous treatment with Oxaliplatin contained regimen. (Including adjuvant chemotherapy) 14.Life expectancy estimated 2 months, and more. 15.Vital organ functions (listed below) are preserved within 14 days prior to entry. i. White blood cell count 3500/mm3>= (Neutrophils>=1500/mm3) ii. Platelets>=100,000/mm3 iii. Total Bilirubin>=upper limit of normal (ULN)*1.5 iv. AST and ALT<=upper limit of normal (ULN)*2.5 (<=ULN*5 in case of liver metastasis) v. Hemoglobin>=9.0 g/dl vi. Serum creatinine<=upper limit of normal (ULN) vii. Urinary protein >= grade1 (+1) 16.Written informed consent.
Exclusion criteria
Exclusion criteria: 1.Hypersensitivity or History of the severe hypersensitivity for Bevacizumab, Fluorouraciland Leucovorin. 2.Prior abdominal irradiation for colorectal cancer. 3.CNS metastases or brain cancer confirmed by imaging (When it is suspected, imaging confirmation is required). 4.Complication of cerebrovascular disease or its symptoms within 1 year. 5.With sever complication (Intestinal paralysis, Intestinal obstruction, Interstitial pneumonitis or Pulmonary fibrosis, Uncontrolled diabetes mellitus, Hypertension, cardiac failure, Renal failure, Liver dysfunction, and so on). 6.With complication of history of Gastrointestinal perforation, Intestinal tract paralysis, or Ileus within 1 year. 7.Massive pleural or Ascites that required drainage. 8.Uncontrolled Peptic ulcer. 9.Uncontrolled Diarrhea. 10.Uncontrolled Infection. 11.Diathesis of Bleeding (history of Hemoptysis, including cavitation and/or necrosis in Lung metastasis confirmed by imaging), Coagulopathy or Abnormality of coagulation factor 12.Administrated Antithrombotic drug or drug affected to Congealing Fibrinogenolysis System within 14 days before enrollment (Except for low-dose of Aspirin.) 13.Active multiple primary cancer. 14.Pregnant women, possibly pregnant women, wishing to become pregnant, and nursing mothers. 15.With mental disorder or psychological symptoms which disturb registration to this study. 16.Not appropriate for the study at the physician's assessment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression free survival [PFS] | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival-1[OS-1 defined as the time duration from enrollment to death due to any cause.] The second progression-free survival (2nd PFS)[Defined as the time duration from the date of initiation of the first-line therapy to investigator-assessed disease progression or patient death due to any cause after starting the second-line treatment.] Overall survival-2 [OS-2 defined as the time duration from the date of initiation of each therapy to death due to any cause.] Response Rate Disease Control RateTime to Treatment Failure Safety | — |
Countries
Japan
Contacts
Public ContactKenji Katsumata
Tokyo Medical University Third Department of Surgery
Outcome results
None listed