A Phase Ib, Dose Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of Humanized Anti-VEGF Monoclonal Antibody(Sevacizumab) Injection Plus FOLFIRI in Chinese Patients With Metastatic Colorectal Cancer
Overview
- Phase
- Phase 1
- Intervention
- Sevacizumab
- Conditions
- Metastatic Colorectal Cancer
- Sponsor
- Jiangsu Simcere Pharmaceutical Co., Ltd.
- Enrollment
- 36
- Locations
- 3
- Primary Endpoint
- Maximum Tolerated Dose (MTD)
- Last Updated
- 10 years ago
Overview
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).
Investigators
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+)
Arms & Interventions
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
Intervention: Sevacizumab
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
Intervention: Irinotecan
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
Intervention: 5-FU
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
Intervention: Leucovorin
Outcomes
Primary Outcomes
Maximum Tolerated Dose (MTD)
Time Frame: up to 56 days
Secondary Outcomes
- 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)