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

Simcere

Status and phase

Unknown

Phase 1

Conditions

Metastatic Colorectal Cancer

Treatments

Drug: Sevacizumab

Drug: Irinotecan

Drug: 5-FU

Drug: Leucovorin

Study type

Interventional

Funder types

Industry

Identifiers

NCT02453464

SIM129-mCRC-01

Details and patient eligibility

About

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).

Enrollment

36 estimated patients

Sex

All

Ages

18 to 74 years old

Volunteers

No Healthy Volunteers

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