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

Metastatic Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02453464
• Other study ID #: SIM129-mCRC-01
• Status: Recruiting
• Phase: Phase 1
• First received: May 19, 2015
• Last updated: April 19, 2016
• Start date: August 2015

Study information

• Verified date: April 2016
• Source: Jiangsu Simcere Pharmaceutical Co., Ltd.
• Contact: Haijun Li, MS
• Phone: 86-025-85560000
• Email: lihaijun[@]simcere.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 74 Years

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• Sevacizumab
escalating doses of Sevacizumab : 3mg/kg,4mg/kg,5mg/kg
• Irinotecan
Irinotecan: IV solution, IV over 90 minutes, 180 mg/m², Every 14 days, Until disease progression/toxicity
• 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
• Leucovorin
Leucovorin: IV solution, IV over 2 hours, 400 mg/m², Every 14 days, Until disease progression/toxicity

Locations

Country	Name	City	State
China	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

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu Simcere Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD)		up to 56 days	Yes
Secondary	Adverse Events (NCI-CTC 4.0)		28 days after the last dose	Yes
Secondary	Plasma pharmacokinetics (PK) parameters for Sevacizumab		Cycle 1(Day3, Day4, Day7, Day10, Day13); Cycle 2-4(Day1);Cycle 4(Day1, Day2, Day5, Day8 ,Day11)	No
Secondary	Plasma pharmacokinetics (PK) parameters (Cmax, Tmax, AUC, T1/2) for Irinotecan and its major metabolite SN-38		Day1, Day2, Day3, Day15, Day16, Day17	No
Secondary	Plasma pharmacokinetics (PK) parameters for 5-FU		Day1, Day3, Day15, Day17	No
Secondary	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	No
Secondary	Objective Response Rate (ORR)		up to 3 years from date of registration	No
Secondary	Disease Control Rate (DCR)		up to 3 years from date of registration	No
Secondary	Progression Free Survival (PFS)		up to 3 years from date of registration	No
Secondary	Overall Survival (OS)		up to 3 years from date of registration	No