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

• ClinicalTrials.gov Identifier: NCT02658734
• Recruitment Status: Completed
• First Posted: January 20, 2016
• Last Update Posted: October 29, 2020
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
HER2 Positive Breast Cancer, Metastatic Breast Cancer, Locally Advanced Breast Cancer	Drug: Trastuzumab emtansine	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 71 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: 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
• Actual Study Start Date: November 1, 2016
• Actual Primary Completion Date: December 14, 2019
• Actual Study Completion Date: December 14, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Severity of Adverse Events [ Time Frame: Up to approximately 3 years ]
2. Percentage of Participants With Adverse Events [ Time Frame: Up to approximately 3 years ]

Secondary Outcome Measures :

1. Percentage of Participants With Serious Adverse Events (SAEs) [ Time Frame: Up to approximately 3 years ]
2. Severity of SAEs as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03 [ Time Frame: Up to approximately 3 years ]
3. Percentage of Participants With Non-Serious Adverse Events of Special Interest [ Time Frame: Up to approximately 3 years ]
4. Laboratory Results Abnormalities [ Time Frame: Up to approximately 3 years ]
5. Percentage of Participants With Adverse Events Leading to Discontinuation of Study Medication [ Time Frame: Up to approximately 3 years ]
6. Percentage of Participants With Adverse Events Leading to Modification of Study Medication [ Time Frame: Up to approximately 3 years ]
7. Percentage of Participants With Adverse Events Leading to Interruption of Study Medication [ Time Frame: Up to approximately 3 years ]
8. Exposure to Study Medication, as Measured by the Area Under the Concentration-Time Curve (AUC) [ Time Frame: Up to approximately 3 years ]
9. Percentage of Participants With Drug-Induced Liver Injury Meeting Hy's Law Criteria [ Time Frame: Up to approximately 3 years ]
10. Percentage of Participants With Congestive Heart Failure [ Time Frame: Up to approximately 3 years ]
11. Left Ventricular Ejection Fraction (LVEF) Decrease as Measured by Echocardiogram [ Time Frame: Up to approximately 3 years ]
12. Overall Response Rate (ORR) [ Time Frame: Up to approximately 3 years ]
13. Progression-Free Survival (PFS) [ Time Frame: Up to approximately 3 years ]
14. Overall Survival (OS) [ Time Frame: Up to approximately 3 years ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

India

Indraprastha Apollo Hospitals

New Delhi, Delhi, India, 110076

Rajiv Gandhi Cancer Inst.&Research Center; Medical Oncology

New Delhi, Delhi, India, 110085

Max Super Speciality Hospital; Medical Oncology

North WEST Delhi, Delhi, India, 110088

Apollo Hospitals International Limited

Gandhinagar, Gujarat, India, 382428

Manipal Hospital; Department of Oncology

Bangalore, Karnataka, India, 560017

Tata Memorial Hospital; Dept of Medical Oncology

Mumbai, Maharashtra, India, 400012

Jehangir Hospital

Pune, Maharashtra, India, 411001

Christian Medical College & Hospital; Medicine

Vellore, Tamil NADU, India, 632004

Healthcare Global Enterprises Limited

Bangalore, India, 560027

Artemis Health Institute

Gurgaon, India, 122001

Fortis Memorial Research Institute; Department of Medical Oncology & Haematology

Gurgaon, India, 122002

Sir Gangaram Hospital; Medical Oncology

New Delhi, India, 110 060

Max Super Speciality Hospital

New Delhi, India, 110017

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02658734
• Other Study ID Numbers: ML29662; 2008-005713-22 ( EudraCT Number )
• First Posted: January 20, 2016
• Last Update Posted: October 29, 2020
• Last Verified: October 2020

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Trastuzumab; Ado-trastuzumab emtansine; Maytansine; Antineoplastic Agents, Immunological; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action