NCT02453464Unknown1 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 入组人数
- 36
- 试验地点
- 3
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Sevacizumab+FOLFIRI
Experimental
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
干预措施: Sevacizumab (Drug)
Sevacizumab+FOLFIRI
Experimental
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
干预措施: Irinotecan (Drug)
Sevacizumab+FOLFIRI
Experimental
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
干预措施: 5-FU (Drug)
Sevacizumab+FOLFIRI
Experimental
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
干预措施: Leucovorin (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: up to 56 days
次要结局
- 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)
研究者
研究点 (3)
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