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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: humanized anti-HER2 antibody
* Drug: Vinorelbine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: combination agent group<br> | Drug: humanized anti-HER2 antibody<br>* 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.<br>* Other names: brand name:Cipterbin®;Drug: Vinorelbine<br>* Vinorelbine was administered weekly at a dose of 25 mg/m2 on day 1, 8 and 21 every 4 weeks<br>* Other names: brand name:NAVELBINE®;|
| Experimental: single agent group<br>In this arm, patients would be treated with Cipterbin® for 12 or 24 weeks | Drug: humanized anti-HER2 antibody<br>* 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.<br>* Other names: brand name:Cipterbin®;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HER2-Overexpressed