A Study of Trastuzumab Emtansine in Indian Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Unresectable Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Treatment With Trastuzumab and a Taxane

Study Overview
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Brief Summary
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This is a Phase IV, single-arm, multicenter, open-label clinical trial designed to assess the safety of trastuzumab emtansine in Indian patients with HER2-positive unresectable locally advanced breast cancer (LABC) or metastatic breast cancer (mBC) who have received prior treatment with trastuzumab and a taxane.

Official Title
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A Multicenter, Open-Label, Single-Arm, Phase IV Study of Trastuzumab Emtansine in Indian Patients With HER2-Positive Unresectable Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Treatment With Trastuzumab and a Taxane

Conditions
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HER2 Positive Breast Cancer, Metastatic Breast Cancer, Locally Advanced Breast Cancer

Intervention / Treatment
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* Drug: Trastuzumab emtansine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prospectively confirmed HER2-positive (i.e., IHC 3+ or IHC 2+ and gene amplified by fluorescence in situ hybridization [FISH] positive) as assessed on primary tumor and/or metastatic site Documented progression of unresectable, locally advanced, or mBC, determined by the investigator Left ventricular ejection fraction (LVEF) >/= 50% by echocardiogram (ECHO) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 A negative serum Beta-Human Chorionic Gonadotropin (Beta-HCG) test for women of childbearing potential (premenopausal or not meeting the definition of postmenopausal i.e. >/= 12 months of amenorrhea), and women who have not undergone surgical sterilization (i.e., absence of ovaries and/or uterus) For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two adequate non-hormonal methods of contraception, including at least one method with a failure rate of <1% per year, during the treatment period and for at least 7 months after the last dose of study drug For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm. With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of <1% per year during the treatment period and for at least 7 months plus 90 days (a spermatogenesis cycle) after the last dose of study drug. Men must refrain from donating sperm during this same period. With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 7 months after the last dose of study drug. Exclusion Criteria: Prior treatment with trastuzumab emtansine Prior treatment with lapatinib or lapatinib with capecitabine or non-comparable biologic or biosimilar of trastuzumab Peripheral neuropathy of Grade >/= 3 per the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE [version 4.03]) History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage 1 uterine cancer, synchronous or previously diagnosed HER2-positive breast cancer, or cancers with a similar curative outcome as those mentioned above History of receiving any anti-cancer drug/biologic or investigational treatment within 21 days prior to enrollment except hormone therapy, which can be given up to 7 days prior to enrollment; recovery of treatment-related toxicity consistent with other eligibility criteria History of exposure to cumulative doses of anthracyclines, as defined in the protocol History of radiation therapy within 14 days of enrollment Brain metastases that are untreated, symptomatic, or require therapy to control symptoms, as well as a history of radiation, surgery, or other therapy, including steroids, to control symptoms from brain metastases within 2 months (60 days) before enrollment CNS only disease History of a decrease in LVEF to < 40% or symptomatic congestive heart failure (CHF) with previous trastuzumab treatment History of symptomatic chronic heart failure (New York Heart Association [NYHA] Classes II-IV) or serious cardiac arrhythmia requiring treatment History of myocardial infarction or unstable angina within 6 months of enrollment Current dyspnea at rest due to complications of advanced malignancy or requirement for continuous oxygen therapy Current severe, uncontrolled systemic disease Pregnancy or lactation Concurrent, serious, uncontrolled infections or current known infection with human immunodeficiency virus (HIV) or active hepatitis B and/or hepatitis C. For patients who are known carriers of hepatitis B virus (HBV), active hepatitis B infection must be ruled out, based on negative serologic testing and/or determination of HBV DNA viral load per local guidelines Presence of conditions that could affect gastrointestinal absorption: malabsorption syndrome, resection of the small bowel or stomach, and ulcerative colitis History of intolerance (such as Grade 3-4 infusion reaction) or known hypersensitivity to trastuzumab or murine proteins or any component of the product Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol

Ages Eligible for Study
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Minimum Age: 18 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: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trastuzumab emtansine<br> | Drug: Trastuzumab emtansine<br>* 3.6 mg/kg intravenously (IV) over 30-90 minutes on day 1 of 21 day cycle, repeated every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of Adverse Events | Adverse events (AEs) grading was completed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. | From cycle 1 up to approximately 3 years | 
| Percentage of Participants With Adverse Events | An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with the treatment. An adverse event was therefore any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsened during the study were also considered as adverse events. | From cycle 1 up to approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Serious Adverse Events (SAEs) | SAEs were defined as any AE that fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/ birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here. | From cycle 1 up to approximately 3 years | 
| Severity of SAEs as Per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03 | Severity refered to the intensity of an AE (e.g., rated as mild, moderate, or severe, or according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria. | From cycle 1 up to approximately 3 years | 
| Percentage of Participants With Non-Serious Adverse Events of Special Interest | Non-serious AEs of special interest included cases of severe drug-induced liver injury and suspected transmission of an infectious agent by the study drug. | From cycle 1 up to approximately 3 years | 
| Laboratory Results Abnormalities |  | From cycle 1 up to approximately 3 years | 
| Percentage of Participants With Adverse Events Leading to Discontinuation of Study Medication |  | From cycle 1 up to approximately 3 years | 
| Percentage of Participants With Adverse Events Leading to Modification of Study Medication |  | From cycle 1 up to approximately 3 years | 
| Percentage of Participants With Adverse Events Leading to Interruption of Study Medication |  | From cycle 1 up to approximately 3 years | 
| Exposure to Study Drug | Exposure to study drug was the amount of study drug received over time (weeks). | From cycle 1 up to approximately 3 years | 
| Percentage of Participants With Drug-Induced Liver Injury Meeting Hy's Law Criteria | Hy's law criteria for potential drug-induced liver injury included elevated aminotransferase enzymes (ALT/AST) with concurrent elevated serum total bilirubin, gross jaundice, clinical disability and the need for hospital care. | From cycle 1 up to approximately 3 years | 
| Percentage of Participants With Congestive Heart Failure |  | From cycle 1 up to approximately 3 years | 
| Change in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram |  | From baseline to every three cycles of treatment up to Cycle 39 Day 1, and at the 2-days post-treatment, safety follow-up visits 1 and 3 | 
| Overall Response Rate (ORR) | ORR was based on the best (confirmed) overall response (BOR). ORR was defined as the number (%) of participants with confirmed complete response (CR) or partial response (PR) where the confirmation was performed no less than 4 weeks after the criteria for response were first met. | From cycle 1 up to approximately 3 years | 
| Progression-Free Survival (PFS) | PFS was defined as the time from the date of enrollment until the date of first documented progression of disease or the date of death (by any cause in the absence of progression) whichever occurred first. | From cycle 1 up to approximately 3 years | 
| Overall Survival (OS) | Overall survival was defined as the time from the date of enrollment until the date of death due to any cause. Participants not known to have died at the time of final analysis were censored based on the last recorded date on which the subject was known to be alive. | From cycle 1 up to approximately 3 years |