a phase ib study of humanized anti-vegf monoclonal antibody (sevacizumab) injection plus folfiri in chinese patients with metastatic colorectal cancer

Conditions: Metastatic Colorectal Cancer

Summary: this is an open-label, multicenter, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics of humanized anti-vegf monoclonal antibody (sevacizumab) injection in combination with folfiri in patients with previously treated metastatic colorectal cancer. this study includes two stages. stage 1 is the dose-escalation stage. once the maximum tolerated dose (mtd) of sevacizumab has been established, additional patients will be enrolled in the cohort-expansion stage (stage 2).


Eligibility criteria:
inclusion criteria: * histological/cytological confirmed unresectable metastatic colorectal cancer patients who have failed first-line oxaliplatin-based chemotherapy * at least one measurable lesion (according to recist 1.1 ) * at least 4 weeks from the last chemotherapy. if patients received anti-tumor biological products, at least four t1/2 of washout period is needed * toxicity from previous treatment has to restore to ≤ grade 1 (nci ctc4.0) * ecog performance status 0-1 * life expectancy ≥ 3 months * adequate hematologic function: anc ≥ 1.5 × 10\^9 /l, hb ≥ 90 g /l (blood transfusion allowed), plt ≥ 100 ×10\^9 /l; adequate hepatic function: alt ≤ 2.5 × uln, ast ≤ 2.5 × uln, tbil ≤ 1.5 × uln (patients with liver metastases alt ≤ 5 × uln, ast ≤ 5 × uln); adequate renal function: creatinine ≤ 1 × uln; coagulation function: inr ≤ 1.5 × uln, aptt ≤ 1.5 × uln * patients of childbearing potential (male and female) must agree to use reliable methods of contraception until at least 12 weeks after the last dose * patients signed written inform consent * willingness and capability to communicate with investigators and to comply with protocol requirements exclusion criteria: * hcv, tp or hiv antibody positive * previously received anti-vegf protein drugs, such as bevacizumab,sevacizumab * previously treated with irinotecan * history of dihydropyrimidine dehydrogenase deficiency * patients with alcohol or drug dependence * participation in other clinical trials within 4 weeks before enrollment * active or chronic hepatitis b infection with hbv dna \> 1.0 \* 10\^3 iu/ml * serious infection requiring intravenous antibiotic therapy * symptomatic brain metastases * patients with proteinuria at screening (urine protein ≥ 1+) * history of abdominal fistula, gastrointestinal perforation, abdominal abscess within 6 months prior to enrollment * history of intestinal obstruction, inflammatory bowel disease, or other intestinal diseases with chronic diarrhea as the major symptom * serious non-healing wounds, ulcers or fractures * major surgery (excluding biopsy) or significant trauma within 4 weeks prior to enrollment * active bleeding within 3 months prior to enrollment * bleeding diathesis or coagulation disorder * history of arterial or venous thrombosis * history of myocardial infarction or stroke within 6 months prior to enrollment * unstable angina, congestive heart failure, new york heart association (nyha) class ii heart failure, uncontrollable arrhythmia, uncontrolled hypertension * expected to receive surgery during the study or within 1 month after the last dose * the investigators consider the patients are not suitable for this trial * pregnant and lactating women * known allergies to any excipient in the study drug * patients can not complete this study for any other reason