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

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

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.

Study Overview

• Status: Completed
• Conditions: HER2 Positive Breast Cancer, Metastatic Breast Cancer, Locally Advanced Breast Cancer
• Intervention / Treatment: Drug: Trastuzumab emtansine

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• India
  • Bangalore, India, 560027
    • HealthCare Global Enterprises Limited
  • Gurgaon, India, 122001
    • Artemis Health Institute
  • Gurgaon, India, 122002
    • Fortis Memorial Research Institute; Department of Medical Oncology & Haematology
  • New Delhi, India, 110017
    • Max Super Speciality Hospital
  • New Delhi, India, 110 060
    • Sir Gangaram Hospital; Medical Oncology
  • Delhi
    • New Delhi, Delhi, India, 110076
      • Indraprastha Apollo Hospitals
    • New Delhi, Delhi, India, 110085
      • Rajiv Gandhi Cancer Inst.&Research Center; Medical Oncology
    • North WEST Delhi, Delhi, India, 110088
      • Max Super Speciality Hospital; Medical Oncology
  • Gujarat
    • Gandhinagar, Gujarat, India, 382428
      • Apollo Hospitals International Limited
  • Karnataka
    • Bangalore, Karnataka, India, 560017
      • Manipal Hospital; Department of Oncology
  • Maharashtra
    • Mumbai, Maharashtra, India, 400012
      • Tata Memorial Hospital; Dept of Medical Oncology
    • Pune, Maharashtra, India, 411001
      • Jehangir Hospital
  • Tamil NADU
    • Vellore, Tamil NADU, India, 632004
      • Christian Medical College & Hospital; Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Actual): December 14, 2019
• Study Completion (Actual): December 14, 2019

Study Registration Dates

• First Submitted: January 15, 2016
• First Submitted That Met QC Criteria: January 19, 2016
• First Posted (Estimate): January 20, 2016

Study Record Updates

• Last Update Posted (Actual): April 2, 2021
• Last Update Submitted That Met QC Criteria: March 31, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Trastuzumab; Maytansine; Ado-Trastuzumab Emtansine
• Other Study ID Numbers: ML29662