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

NCT ID: NCT02453464

Last Updated: 2016-04-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31

Brief 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).

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sevacizumab+FOLFIRI

Two weeks as one cycle. Cycle 1: FOLFIRI on day1-2, Sevacizumab on day3; Cycle 2 and after: Sevacizumab on day 1, and then FOLFIRI on day1-2

Group Type: EXPERIMENTAL

Sevacizumab

Intervention Type: DRUG

escalating doses of Sevacizumab : 3mg/kg，4mg/kg，5mg/kg

Irinotecan

Intervention Type: DRUG

Irinotecan: IV solution, IV over 90 minutes, 180 mg/m², Every 14 days, Until disease progression/toxicity

5-FU

Intervention Type: DRUG

5-FU: IV solution, IV bolus over 2-4 minutes, 400 mg/m²; IV infusion over 46 hours, 2400 mg/m²; Every 14 days, Until disease progression/toxicity

Leucovorin

Intervention Type: DRUG

Leucovorin: IV solution, IV over 2 hours, 400 mg/m², Every 14 days, Until disease progression/toxicity

Interventions

Sevacizumab

escalating doses of Sevacizumab : 3mg/kg，4mg/kg，5mg/kg

Intervention Type: DRUG

Irinotecan

Irinotecan: IV solution, IV over 90 minutes, 180 mg/m², Every 14 days, Until disease progression/toxicity

Intervention Type: DRUG

5-FU

5-FU: IV solution, IV bolus over 2-4 minutes, 400 mg/m²; IV infusion over 46 hours, 2400 mg/m²; Every 14 days, Until disease progression/toxicity

Intervention Type: DRUG

Leucovorin

Leucovorin: IV solution, IV over 2 hours, 400 mg/m², Every 14 days, Until disease progression/toxicity

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jiangsu Simcere Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jin Li, MD

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

The First Bethune Hospital of Jilin University

Changchun, Jilin, China

Site Status: RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

The First Hospital of Zhejiang Province

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Haijun Li, MS

Role: CONTACT

lihaijun@simcere.com

86-025-85560000 ext. 1625

Facility Contacts

Yanhua Ding

Role: primary

Jin Li

Role: primary

Nong Xu

Role: primary

Other Identifiers

SIM129-mCRC-01

Identifier Type: -

Identifier Source: org_study_id