Clinical trial NCT02453464: A Phase Ib Study of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab) Injection Plus FOLFIRI in Chinese Patients With Metastatic Colorectal Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2015-05-25
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: up to 56 days
Secondary outcomes:
measure: Adverse Events (NCI-CTC 4.0)
timeFrame: 28 days after the last dose
measure: Plasma pharmacokinetics (PK) parameters for Sevacizumab
timeFrame: Cycle 1(Day3, Day4, Day7, Day10, Day13); Cycle 2-4(Day1);Cycle 4(Day1, Day2, Day5, Day8 ,Day11)
measure: Plasma pharmacokinetics (PK) parameters (Cmax, Tmax, AUC, T1/2) for Irinotecan and its major metabolite SN-38
timeFrame: Day1, Day2, Day3, Day15, Day16, Day17
measure: Plasma pharmacokinetics (PK) parameters for 5-FU
timeFrame: Day1, Day3, Day15, Day17
measure: Potential biomarkers, including VEGF and ADA
timeFrame: 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
measure: Objective Response Rate (ORR)
timeFrame: up to 3 years from date of registration
measure: Disease Control Rate (DCR)
timeFrame: up to 3 years from date of registration
measure: Progression Free Survival (PFS)
timeFrame: up to 3 years from date of registration
measure: Overall Survival (OS)
timeFrame: up to 3 years from date of registration
Other outcomes:
Locations:
city: Changchun
country: China
facility: The First Bethune Hospital of Jilin University
state: Jilin
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Hangzhou
country: China
facility: The First Hospital of Zhejiang Province
state: Zhejiang
Study officials:
affiliation: Fudan University
name: Jin Li, MD
role: PRINCIPAL_INVESTIGATOR
References: