Clinical trial NCT02658734: 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: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HER2 Positive Breast Cancer, Metastatic Breast Cancer, Locally Advanced Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-01-20
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.


Eligibility 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

Primary outcomes:
measure: Severity of Adverse Events
timeFrame: From cycle 1 up to approximately 3 years
measure: Percentage of Participants With Adverse Events
timeFrame: From cycle 1 up to approximately 3 years
Secondary outcomes:
measure: Percentage of Participants With Serious Adverse Events (SAEs)
timeFrame: From cycle 1 up to approximately 3 years
measure: Severity of SAEs as Per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03
timeFrame: From cycle 1 up to approximately 3 years
measure: Percentage of Participants With Non-Serious Adverse Events of Special Interest
timeFrame: From cycle 1 up to approximately 3 years
measure: Laboratory Results Abnormalities
timeFrame: From cycle 1 up to approximately 3 years
measure: Percentage of Participants With Adverse Events Leading to Discontinuation of Study Medication
timeFrame: From cycle 1 up to approximately 3 years
measure: Percentage of Participants With Adverse Events Leading to Modification of Study Medication
timeFrame: From cycle 1 up to approximately 3 years
measure: Percentage of Participants With Adverse Events Leading to Interruption of Study Medication
timeFrame: From cycle 1 up to approximately 3 years
measure: Exposure to Study Drug
timeFrame: From cycle 1 up to approximately 3 years
measure: Percentage of Participants With Drug-Induced Liver Injury Meeting Hy's Law Criteria
timeFrame: From cycle 1 up to approximately 3 years
measure: Percentage of Participants With Congestive Heart Failure
timeFrame: From cycle 1 up to approximately 3 years
measure: Change in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram
timeFrame: 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
measure: Overall Response Rate (ORR)
timeFrame: From cycle 1 up to approximately 3 years
measure: Progression-Free Survival (PFS)
timeFrame: From cycle 1 up to approximately 3 years
measure: Overall Survival (OS)
timeFrame: From cycle 1 up to approximately 3 years
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Indraprastha Apollo Hospitals
state: Delhi
city: New Delhi
country: India
facility: Rajiv Gandhi Cancer Inst.&Research Center; Medical Oncology
state: Delhi
city: North WEST Delhi
country: India
facility: Max Super Speciality Hospital; Medical Oncology
state: Delhi
city: Gandhinagar
country: India
facility: Apollo Hospitals International Limited
state: Gujarat
city: Bangalore
country: India
facility: Manipal Hospital; Department of Oncology
state: Karnataka
city: Mumbai
country: India
facility: Tata Memorial Hospital; Dept of Medical Oncology
state: Maharashtra
city: Pune
country: India
facility: Jehangir Hospital
state: Maharashtra
city: Vellore
country: India
facility: Christian Medical College & Hospital; Medicine
state: Tamil NADU
city: Bangalore
country: India
facility: Healthcare Global Enterprises Limited
city: Gurgaon
country: India
facility: Artemis Health Institute
city: Gurgaon
country: India
facility: Fortis Memorial Research Institute; Department of Medical Oncology & Haematology
city: New Delhi
country: India
facility: Sir Gangaram Hospital; Medical Oncology
city: New Delhi
country: India
facility: Max Super Speciality Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: