Health Condition 1: C509- Malignant neoplasm of breast of unspecified site
Conditions
Interventions
Intervention1: Test Product (Hetero-Trastuzumab) (T): Test product will be administered at a loading dose of 8 mg/kg over 90 min on day 1 followed by 6 mg/kg over 30-90 min every 3 weekly subsequent d
Sponsors
Hetero Biopharma Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1. Female patients of age 18 to 65 years (both inclusive) 2. Ability to comply with study and follow-up procedures and provide written informed consent 3. Have pathologically confirmed, uni-dimensionally measurable metastatic breast cancer 4. Documented evidence of HER2-overexpression by immunohistochemistry (IHC) (defined as IHC3+, or IHC2+ with FISH confirmation) or HER2 gene amplification by fluorescence in-situ hybridization (FISH) (as defined by a ratio >2.0) or positive chromogenic in-situ hybridization (CISH) result 5. Have target lesions outside prior radiation fields 6. Have Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 7. Patients who have received adjuvant radiotherapy as part of the treatment of early breast cancer are eligible if the last fraction of radiotherapy was administered at least 6 months prior to randomization. 8. Radiotherapy administered for the relief of metastatic bone pain other than the sole site of measurable diseases is allowed, but: - no more than 25% of marrow-bearing bone should have been irradiated, - the last fraction of radiotherapy should not have been administered within 4 weeks prior to randomization, - patients must have recovered from all treatment-related toxicities prior to randomization. 9. Have never been treated with trastuzumab, or prior trastuzumab and chemotherapy (taxane included) or trastuzumab alone as neoadjuvant/ adjuvant treatment is discontinued >12 months prior to randomization. 10. Bisphosphonate therapy for bone metastases is allowed; however, treatment must be initiated prior to the first dose of randomized therapy. Prophylactic use of bisphosphonates in patients without bone diseases is not permitted, except for the treatment of osteoporosis.
Exclusion criteria
Exclusion criteria: 1. Patients with history of hypersensitivity to the trastuzumab or to drugs with similar chemical structures, or to any of the excipients, or to murine proteins 2. Male patients with metastatic breast cancer 3. Patients with history of severe hypersensitivity reaction to Paclitaxel, or to any of the excipients. 4. Patients received prior chemotherapy for metastatic breast cancer. However, the following patients with prior chemotherapy will be allowed: - Neo-adjuvant anthracycline 12 months prior to randomization is allowed - Neo-adjuvant taxanes 12 months prior to randomization is allowed - Neo-adjuvant trastuzumab or any other monoclonal antibody 12 months prior to randomization is allowed; - hormonal therapy administered in neo-adjuvant setting only 5. Patients with current clinical or radiographic evidence of central nervous system metastases 6. Patients receiving concurrent immunotherapy or hormonal therapy. 7. Patients with a history or evidence of cardiovascular diseases including congestive heart failure (CHF) of Grade-III/IV New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia, unstable angina pectoris, myocardial infarction. 8. Patients with an abnormal LVEF ( 9. Patients with current uncontrolled hypertension (systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg). 10. Patients with severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy. 11. Patients with prior malignancy within the last 5 years that might affect breast cancer diagnosis or assessment. 12. Patients have had prior mediastinal irradiation (except internal mammary-node irradiation for the present breast cancer). 13. Patients received cumulative doses of anthracycline exceeding 360 mg/m2 of body surface area for doxorubicin, 720 mg/m2 for epirubicin, 120 mg/m2 for mitoxantrone, 90 mg/m2 for idarubicin, or the equivalent of 360 mg/m2 of doxorubicin for other anthracyclines such as liposomal doxorubicin. If more than one anthracycline has been used, then the cumulative dose must not exceed the equivalent of 360 mg/m2 of doxorubicin. 14. Patients with following laboratory parameter measurements within 3 weeks prior to randomization: - Neutrophils =1500/mm3 - Platelets =100 000/mm3 - Hemoglobin =9 g/dl - Creatinine level = 1.5 × upper limit of normal (ULN) - Bilirubin level = 1.5 × ULN - AST and ALT levels = 2.5 × ULN (5 x ULN if liver metastases) - Alkaline phosphatase level = 2.5 × ULN (4.0 x ULN if liver/ bone metastases) 15. Patients with any other medical or psychiatric condition that could compromise study participation. 16. Patients received treatment with any other investigational drug in the last 30 days before study entry, or within less than five halflives after receiving the previous investigational drug. 17. Patients with current known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). 18. Patients who are pregnant or a nursing mother. 19. Patients with a history or suspicion of unreliability, poor cooperation or non-compliance with medical treatment. 20. Patients with any concurrent disease or condition that, in the opinion of the investigator, wo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare Objective Response Rate (ORR) achieved at end of 12 weeks.Timepoint: 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| - Comparative incidence and titres of anti-Trastuzumab antibodies (Immunogenicity) at 12 and 24 weeks.Timepoint: 12 and 24 weeks;- Comparative safety and tolerability for treatment emergent adverse events by monitoring of significant clinical signs and symptoms and laboratory abnormalities during treatmentTimepoint: 24 weeks;- Compare single dose pharmacokinetic parameters of two formulations of Trastuzumab (test and reference) in terms of AUC0-t and Cmax [Cycle 1 dosing]Timepoint: Cycle 1;- Exploratory shed HER2 extracellular domain (ECD) levels at baseline, at the end of 12 weeks and at the end of 24 weeks.Timepoint: 12 and 24 weeks;- Progression free survival (PFS)Timepoint: 24 weeks;- To compare Objective Response Rate (ORR) achieved at end of 24 weeks.Timepoint: 24 weeks | — |
Countries
India
Contacts
Public ContactDr Shubhadeep Sinha
Hetero Drugs Limited
Outcome results
None listed