Metastatic Breast Cancer
Conditions
Keywords
HER2-Overexpressed
Brief summary
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
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.
Interventions
DRUGhumanized 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.
DRUGVinorelbine
Vinorelbine was administered weekly at a dose of 25 mg/m2 on day 1, 8 and 21 every 4 weeks
Sponsors
Shanghai CP Guojian Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate | up to 24 weeks | according to RECIST 1.0 (Response Evaluation Criteria In Solid Tumors) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| One-year survival rate | 1 year | — |
| Number of participants with adverse events | up to 24 weeks | Adverse events was recorded according to NCI CTC 2.0 (National Cancer Institute common toxicity criteria). |
| Overall control of disease | up to 24 weeks | defined as overall response rate plus stable disease, by RECIST 1.0 |
Countries
China
Outcome results
None listed