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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

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ClinicalTrials.gov Identifier: NCT02658734
Recruitment Status : Completed
First Posted : January 20, 2016
Results First Posted : February 9, 2021
Last Update Posted : February 9, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE January 15, 2016
First Posted Date  ICMJE January 20, 2016
Results First Submitted Date  ICMJE December 10, 2020
Results First Posted Date  ICMJE February 9, 2021
Last Update Posted Date February 9, 2021
Actual Study Start Date  ICMJE November 1, 2016
Actual Primary Completion Date December 14, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 21, 2021)
  • Severity of Adverse Events [ Time Frame: From cycle 1 up to approximately 3 years ]
    Adverse events (AEs) grading was completed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03.
  • Percentage of Participants With Adverse Events [ Time Frame: From cycle 1 up to approximately 3 years ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 19, 2016)
  • Severity of Adverse Events [ Time Frame: Up to approximately 3 years ]
  • Percentage of Participants With Adverse Events [ Time Frame: Up to approximately 3 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 21, 2021)
  • Percentage of Participants With Serious Adverse Events (SAEs) [ Time Frame: From cycle 1 up to approximately 3 years ]
    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.
  • Severity of SAEs as Per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03 [ Time Frame: From cycle 1 up to approximately 3 years ]
    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.
  • Percentage of Participants With Non-Serious Adverse Events of Special Interest [ Time Frame: From cycle 1 up to approximately 3 years ]
    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.
  • Laboratory Results Abnormalities [ Time Frame: From cycle 1 up to approximately 3 years ]
  • Percentage of Participants With Adverse Events Leading to Discontinuation of Study Medication [ Time Frame: From cycle 1 up to approximately 3 years ]
  • Percentage of Participants With Adverse Events Leading to Modification of Study Medication [ Time Frame: From cycle 1 up to approximately 3 years ]
  • Percentage of Participants With Adverse Events Leading to Interruption of Study Medication [ Time Frame: From cycle 1 up to approximately 3 years ]
  • Exposure to Study Drug [ Time Frame: From cycle 1 up to approximately 3 years ]
    Exposure to study drug was the amount of study drug received over time (weeks).
  • Percentage of Participants With Drug-Induced Liver Injury Meeting Hy's Law Criteria [ Time Frame: From cycle 1 up to approximately 3 years ]
    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.
  • Percentage of Participants With Congestive Heart Failure [ Time Frame: From cycle 1 up to approximately 3 years ]
  • Change in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram [ Time Frame: 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) [ Time Frame: From cycle 1 up to approximately 3 years ]
    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.
  • Progression-Free Survival (PFS) [ Time Frame: From cycle 1 up to approximately 3 years ]
    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.
  • Overall Survival (OS) [ Time Frame: From cycle 1 up to approximately 3 years ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 19, 2016)
  • Percentage of Participants With Serious Adverse Events (SAEs) [ Time Frame: 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 [ Time Frame: Up to approximately 3 years ]
  • Percentage of Participants With Non-Serious Adverse Events of Special Interest [ Time Frame: Up to approximately 3 years ]
  • Laboratory Results Abnormalities [ Time Frame: Up to approximately 3 years ]
  • Percentage of Participants With Adverse Events Leading to Discontinuation of Study Medication [ Time Frame: Up to approximately 3 years ]
  • Percentage of Participants With Adverse Events Leading to Modification of Study Medication [ Time Frame: Up to approximately 3 years ]
  • Percentage of Participants With Adverse Events Leading to Interruption of Study Medication [ Time Frame: Up to approximately 3 years ]
  • Exposure to Study Medication, as Measured by the Area Under the Concentration-Time Curve (AUC) [ Time Frame: Up to approximately 3 years ]
  • Percentage of Participants With Drug-Induced Liver Injury Meeting Hy's Law Criteria [ Time Frame: Up to approximately 3 years ]
  • Percentage of Participants With Congestive Heart Failure [ Time Frame: Up to approximately 3 years ]
  • Left Ventricular Ejection Fraction (LVEF) Decrease as Measured by Echocardiogram [ Time Frame: Up to approximately 3 years ]
  • Overall Response Rate (ORR) [ Time Frame: Up to approximately 3 years ]
  • Progression-Free Survival (PFS) [ Time Frame: Up to approximately 3 years ]
  • Overall Survival (OS) [ Time Frame: Up to approximately 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE HER2 Positive Breast Cancer, Metastatic Breast Cancer, Locally Advanced Breast Cancer
Intervention  ICMJE Drug: Trastuzumab emtansine
3.6 mg/kg intravenously (IV) over 30-90 minutes on day 1 of 21 day cycle, repeated every 3 weeks
Study Arms  ICMJE Experimental: Trastuzumab emtansine
Intervention: Drug: Trastuzumab emtansine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 19, 2016)
70
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 14, 2019
Actual Primary Completion Date December 14, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE India
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02658734
Other Study ID Numbers  ICMJE ML29662
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP