A Phase Ib Study of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab) Injection Plus FOLFIRI in Chinese Patients With Metastatic Colorectal Cancer
Phase 1
- Conditions
- Metastatic Colorectal Cancer
- Interventions
- Registration Number
- NCT02453464
- Lead Sponsor
- Jiangsu Simcere Pharmaceutical Co., Ltd.
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 36
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Sevacizumab+FOLFIRI Sevacizumab 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 Sevacizumab+FOLFIRI Leucovorin 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 Sevacizumab+FOLFIRI Irinotecan 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 Sevacizumab+FOLFIRI 5-FU 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
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose (MTD) up to 56 days
- Secondary Outcome Measures
Name Time Method Adverse Events (NCI-CTC 4.0) 28 days after the last dose Plasma pharmacokinetics (PK) parameters (Cmax, Tmax, AUC, T1/2) for Irinotecan and its major metabolite SN-38 Day1, Day2, Day3, Day15, Day16, Day17 Plasma pharmacokinetics (PK) parameters for 5-FU Day1, Day3, Day15, Day17 Plasma pharmacokinetics (PK) parameters for Sevacizumab Cycle 1(Day3, Day4, Day7, Day10, Day13); Cycle 2-4(Day1);Cycle 4(Day1, Day2, Day5, Day8 ,Day11) Objective Response Rate (ORR) up to 3 years from date of registration Potential biomarkers, including VEGF and ADA VEGF:Cycle 1(Day3, Day4, Day7, Day10, Day13); Cycle 2-4(Day1);Cycle 4(Day1, Day2, Day5, Day8, Day11); ADA : within 15 minutes before each Sevacizumab administration Progression Free Survival (PFS) up to 3 years from date of registration Overall Survival (OS) up to 3 years from date of registration Disease Control Rate (DCR) up to 3 years from date of registration
Trial Locations
- Locations (3)
The First Bethune Hospital of Jilin University
🇨🇳Changchun, Jilin, China
The First Hospital of Zhejiang Province
🇨🇳Hangzhou, Zhejiang, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China