Study of Cipterbin®, Used Alone or With Vinorelbine in Patients With HER2/Neu-overexpressed Metastatic Breast Cancer

An Open-Label Randomized Phase II Study of Cipterbin® or Cipterbin® in Combination With Vinorelbine in Patients With HER2/Neu-overexpressed Metastatic Breast Cancer (MBC)

The HER2 gene (also known as HER2/neu and ErbB2 gene) is overexpressed in 20-30% of human breast cancers and leads to a particularly aggressive form of the disease. Trastuzumab,a humanized anti-HER2/neu receptor monoclonal antibody, has been proved a valuable treatment for HER2-positive breast cancer patients.The combination of trastuzumab with chemotherapy has been shown to increase both survival and response rate, in comparison to trastuzumab alone. CMAB302, a biosimilar of trastuzumab, was developed by Shanghai CP Guojian Pharmaceutical Co.Ltd. Efficacy and safety of CMAB302 as a single agent or in combination with vinorelbine were evaluated in patients with HER2-overexpressing metastatic breast cancer.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: humanized anti-HER2 antibody; Drug: Vinorelbine

Detailed Description

The HER2 gene (also known as HER2/neu and ErbB2 gene) is overexpressed in 20-30% of human breast cancers and leads to a particularly aggressive form of the disease. Trastuzumab,a humanized anti-HER2/neu receptor monoclonal antibody, has been proved valuable treatment for HER2-positive breast cancer patients.The combination of trastuzumab with chemotherapy has been shown to increase both survival and response rate, in comparison to trastuzumab alone. CMAB302, a biosimilar of trastuzumab, was developed by Shanghai CP Guojian Pharmaceutical Co.Ltd. Previous Phase I study showed that CMAB302 was well tolerated as monotherapy and the pharmacokinetic data exhibited a non-linear profile over the dose range of 100 to 500 mg, similar to that of trastuzumab. In this study, efficacy and safety of CMAB302 as a single agent or in combination with vinorelbine were evaluated in patients with HER2-overexpressing metastatic breast cancer.

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100021
    • Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• pathologic diagnosis breast cancer
• HER2+ status defined as IHC3+ Staining or in situ hybridization positive at least 1 measurable lesion as per RECIST criteria
• Adequate bone marrow function (absolute neutrophil count >1500/mm3, platelet count >100.000/mm3, hemoglobin >10gr/mm3)
• Adequate liver (bilirubin <1.0 times upper limit of normal and SGOT/SGPT <2.5 times upper limit of normal) and renal function (creatinine <1.5mg/dl)
• Adequate cardiac function (LVEF>50%). Normal electrocardiogram and absence of significant heart disease
• age from 18 to 70y
• Karnofsky performance score ≥ 60
• Life expectancy of greater than 3 months
• Negative HCG pregnancy test for premenopausal women of reproductive capacity and for women less than 12 months after the menopause.
• signed ICF

Exclusion Criteria:

• prior exposure vinorelbine for breast cancer
• prior exposure trastuzumab for breast cancer
• Prior chemotherapy and radiation therapy within the last 4 weeks before enrollment
• use of any other investigational agents within the last 4 weeks before enrollment
• symptomatic, central nervous system metastases
• Hypersensitivity to trial medications
• breastfeeding or pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: combination agent group	Drug: humanized anti-HER2 antibody; Initial dose of 4 mg/kg as an intravenous infusion over 90 minutes then at 2 mg/kg as an intravenous infusion over 30 minutes weekly for 12 weeks. For single agent group, patients with complete response, partial response or stable disease could be treated for 24 weeks.; Other Names: brand name:Cipterbin®; Drug: Vinorelbine; Vinorelbine was administered weekly at a dose of 25 mg/m2 on day 1, 8 and 21 every 4 weeks; Other Names: brand name:NAVELBINE®
Experimental: single agent group; In this arm, patients would be treated with Cipterbin® for 12 or 24 weeks	Drug: humanized anti-HER2 antibody; Initial dose of 4 mg/kg as an intravenous infusion over 90 minutes then at 2 mg/kg as an intravenous infusion over 30 minutes weekly for 12 weeks. For single agent group, patients with complete response, partial response or stable disease could be treated for 24 weeks.; Other Names: brand name:Cipterbin®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	according to RECIST 1.0 (Response Evaluation Criteria In Solid Tumors)	up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
One-year survival rate		1 year
Number of participants with adverse events	Adverse events was recorded according to NCI CTC 2.0 (National Cancer Institute common toxicity criteria).	up to 24 weeks
Overall control of disease	defined as overall response rate plus stable disease, by RECIST 1.0	up to 24 weeks

Collaborators and Investigators

• Sponsor: Shanghai CP Guojian Pharmaceutical Co., Ltd.
• Investigators: Study Chair: Yan Sun, PhD, Cancer Institute and Hospital, Chinese Academy of Medical Sciences; Study Director: Yuankai Shi, PhD, Cancer Institute and Hospital, Chinese Academy of Medical Sciences; Principal Investigator: Zefei Jiang, PhD, Hospital Affiliated to Academy Military Medical Science; Principal Investigator: Jun Ren, PhD, Peking University Cancer Hospital & Institute; Principal Investigator: Kai Li, PhD, Tianjin Medical University Cancer Institute and Hospital; Principal Investigator: Dong Wang, PhD, Daping Hospital & Research Institute of Surgery of the Third Military Medical University

Study record dates

Study Major Dates

• Study Start: July 1, 2005
• Primary Completion (Actual): February 1, 2007
• Study Completion (Actual): May 1, 2007

Study Registration Dates

• First Submitted: September 21, 2011
• First Submitted That Met QC Criteria: September 21, 2011
• First Posted (Estimate): September 23, 2011

Study Record Updates

• Last Update Posted (Estimate): September 23, 2011
• Last Update Submitted That Met QC Criteria: September 21, 2011
• Last Verified: June 1, 2005

More Information

Terms related to this study

• Keywords: HER2-Overexpressed
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antibodies; Vinorelbine
• Other Study ID Numbers: C302MBCⅡ

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No