A Phase Ib Study of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab) Injection Plus FOLFIRI in Chinese Patients With Metastatic Colorectal Cancer

• Status: Unknown status
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
• Treatments: Antibodies; Antibodies, Monoclonal; Bevacizumab; Irinotecan; Leucovorin

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