A Phase Ia, Dose Escalation Study of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab) Injection in Patients With Advanced or Metastatic Solid Tumors

This study is to assess the safety, tolerability and pharmacokinetics of single dose and multiple doses of humanized anti-VEGF monoclonal antibody (Sevacizumab) in patients with advanced or metastatic solid tumors. The secondary objective is to explore the preliminary anti-tumor effects.

Study Overview

• Status: Unknown
• Conditions: Advanced Solid Tumors; Metastatic Solid Tumors
• Intervention / Treatment: Drug: Sevacizumab

• Study Type: Interventional
• Enrollment (Anticipated): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Fudan University Shanghai Cancer Center
    • Contact: Jin Li, MD, PhD; Phone Number: 86-021-61733905

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically confirmed advanced or metastatic malignant solid tumors;
• Patients failed the standard anti-tumor therapy or don't have standard regimen;
• At least one measurable lesion;
• At least 4 weeks from the last chemotherapy, 6 weeks from mitomycin, and nitrosourea treatment. 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, TBIL ≤ 3 × 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.

Exclusion Criteria:

• HCV, TP or HIV antibody positive;
• Previously received anti-VEGF protein drugs, such as bevacizumab;
• Histologically proven squamous cell lung cancer or squamous cell carcinoma of the head and neck;
• Active hepatitis B infection;
• Evidence of serious infection;
• 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;
• 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 (systolic blood pressure> 150 mmHg and/or diastolic blood pressure> 100 mmHg);
• Pregnant and lactating women;
• Known allergies to any excipient in the study drug;
• Patients with alcohol or drug dependence;
• Participation in other clinical trials within 4 weeks before enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sevacizumab; 2mg/kg、5mg/kg、7.5mg/kg、10mg/kg、12.5mg/kg、or 15mg/kg. d1, d29, d43, d57	Drug: Sevacizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Tolerated Dose (MTD)	up to 28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Cmax	d1, d2, d5, d8, d11, d15, d18, d22, d25,d29, d43, d57
tmax	d1, d2, d5, d8, d11, d15, d18, d22, d25,d29, d43, d57
AUC	d1, d2, d5, d8, d11, d15, d18, d22, d25,d29, d43, d57
t1/2	d1, d2, d5, d8, d11, d15, d18, d22, d25,d29, d43, d57
Objective Response Rate (ORR)	d29, d86
Disease Control Rate (DCR)	d29, d86

Collaborators and Investigators

• Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: jin li, MD, PHD, Fudan University

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Anticipated): November 1, 2015
• Study Completion (Anticipated): November 1, 2015

Study Registration Dates

• First Submitted: April 26, 2013
• First Submitted That Met QC Criteria: May 3, 2013
• First Posted (Estimate): May 6, 2013

Study Record Updates

• Last Update Posted (Estimate): March 24, 2015
• Last Update Submitted That Met QC Criteria: March 22, 2015
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: SIM-63-001