Health Condition 1: C509- Malignant neoplasm of breast of unspecified site
Conditions
Interventions
Intervention1: Pertuzumab (ZRC-3277, Cadila Healthcare Ltd.,): 1)Route: Intravenous
2)Frequency: every 3 weeks for 6 cycles
Pertuzumab in combination with Trastuzumab and Docetaxel will
be administer
Sponsors
Zydus Research Centre Cadila Healthcare Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1.Female patients 18 to 65 years of age (both inclusive). 2.Patient with pathologically (histologically or cytologically) confirmed, adenocarcinoma metastatic breast cancer and candidate for chemotherapy. Note: Patients with de-novo Stage IV disease are eligible. 3.With at least one measurable metastatic target lesion (based on RECIST criteria, version1.1). 4.Documentation of following prior to randomization: a)Documentation of HER2 gene amplification by fluorescent in situ hybridization (FISH); as defined by a ratio >2.0) OR documentation of HER2-overexpression by immunohistochemistry (IHC) (defined as IHC3+, or IHC2+ with FISH confirmation) (estrogen receptor/progesterone receptor positive subjects may be enrolled if they are HER2 positive) prior to randomization, see Section 6.4 for detailed criteria) 5. Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1. 6. Left ventricular ejection fraction (LVEF) of = 50% at baseline (within 42 days of randomization) as measured by echocardiography (ECHO) or multiple gated acquisition (MUGA). Note: ECHO is the preferred method. If the patient is randomized, the same method of LVEF assessment (i.e., ECHO or MUGA) must be used throughout the study and it should preferably be obtained at the same institution and preferably by the same assessor) 7. Patient able to understand and willing to give the informed consent and able to comply with the requirements of the study protocol. 8. A woman of childbearing potential must have a negative highly sensitive serum (ß-human chorionic gonadotropin [ß-hCG]) at screening and urine ß-hCG test at randomization. 9. Woman of child-bearing potential must agree to use adequate contraceptive methods that is highly effective (with a failure rate of at least 7 months after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during the study and for a period of 7 months. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
Exclusion criteria
Exclusion criteria: 1. History of anticancer therapy for MBC, with the exception of single prior hormonal regimen for MBC, which must be stopped prior to randomization. Note 1: Anticancer therapy for MBC includes any epidermal growth factor receptor or anti- HER2 agents or vaccines, cytotoxic chemotherapy, or more than one prior hormonal regimen for MBC Note 2: Single prior hormonal regimen for MBC may include more than one hormonal therapy.If a patient is switched to a different hormonal therapy because of disease progression, this will be counted as two regimens, and the patient will not be eligible for the study. If a patient is switched to a different hormonal therapy for reasons other than disease progression (e.g., toxicity or local standard practice), this will be counted as single regimen. 2. History of systemic breast cancer treatment in the neo-adjuvant or adjuvant setting with a disease-free interval from completion of the systemic treatment (excluding hormonal therapy) to metastatic diagnosis of 12 months. 3. History of approved or investigative tyrosine kinase/HER inhibitors for breast cancer in any treatment setting, except trastuzumab used in the neoadjuvant or adjuvant setting. 4. Patients with CNS metastases, except for treated asymptomatic CNS metastases, provided all of the following criteria are met: a. Only supra-tentorial metastases allowed (i.e., no metastases to midbrain, pons, medulla, or spinal cord) b. No evidence of interim progression or hemorrhage after completion of CNS-directed therapy c. No ongoing requirement for corticosteroids as therapy for CNS disease (anticonvulsants at a stable dose are allowed) d. No stereotactic radiation within 14 days or whole-brain radiation within 28 days prior to randomization e. Leptomeningeal disease (i.e. carcinomatous meningitis) 5. History of persistent Grade = 2 hematologic toxicity resulting from previous neoadjuvant or adjuvant therapy (all grades based on National Cancer Institute Common Toxicity Criteria for Adverse Events, Version 5.0 [NCI CTCAE v 5.0]). 6. Current peripheral neuropathy of NCI-CTCAE, Version 5.0, Grade = 3 at randomization. 7. Have a history of congestive heart failure (CHF) of any New York Heart Association (NYHA) criterion, or serious cardiac arrhythmia requiring treatment (except for atrial fibrillation,paroxysmal supraventricular tachycardia). 8. History of myocardial infarction within 6 months before randomization. 9. Current uncontrolled hypertension (systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg), or unstable angina. 10. Current dyspnea at rest due to complications of advanced malignancy or other diseases that require continuous oxygen therapy. 11. History of other malignancy within the previous 5 years, except for carcinoma in situ of the cervix or non- melanoma skin carcinoma that has been previously treated with curative intent. 12. History of exposure to the following cumulative doses of anthracyclines: a. doxorubicin or liposomal doxorubicin > 360 mg/m2 b. epirubicin > 720 mg/m2 c.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare the objective response rate (ORR) following Test Pertuzumab (Cadila Healthcare Ltd.,) plus Trastuzumab and Docetaxel versus Reference Pertuzumab (Perjeta®,Timepoint: Baseline and Cycle 6 | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess the immunogenicity of Pertuzumab (Test Product, Cadila Healthcare Ltd.,) compared to Reference Pertuzumab (Perjeta®, a product of Genentech, Inc.,).Timepoint: baseline and end of the study i.e Day 1, Day 64, and Day 127;To assess the pharmacokinetics of Pertuzumab (Test Product, Cadila Healthcare Ltd.,) compared to Reference Pertuzumab (Perjeta®, a product of Genentech, Inc).Timepoint: At Pre-dose, end of infusion, 3 h, 6 h, 24 h, 48 h, 96 h, 168 h, 336 h and 504 h from the start of infusion of cycle 1. Additionally, Pre-dose blood samples will be withdrawn at Day 43, 64, 85, 106 and Day 127 (EOS);To assess the safety and tolerability of Pertuzumab (Test Product, Cadila Healthcare Ltd.,) compared to reference Pertuzumab (Perjeta®, a product of Genentech, Inc).Timepoint: At Baseline, Cycle 1 to Cycle 6 and EOS i.e throughout the study | — |
Countries
India
Contacts
Public ContactDr Sandip Barvaliya MD
Zydus Research Centre
Outcome results
None listed