This is a study with Trastuzumab Emtansine in Indian Patients who have unresectable Locally advanced or Metastatic Breast cancer, that is HER2-Positive and who already have received treatment with Trastuzumab and a Taxane earlier.
- Conditions
- Health Condition 1: null- Breast Cancer
- Registration Number
- CTRI/2015/10/006258
- Lead Sponsor
- Roche Products India Pvt Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 70
1.Male or female of age >= 18 years
2.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 if primary tumor not available (ISH positivity is defined as a ratio of 2.0 or greater for the number of HER2 gene copies to the number of signals for CEP17, or for single probe tests, a HER2 gene count greater than 4) as determined in a local laboratory that is experienced/certified in HER2-expression testing using an accurate and validated assay
3.Histologically or cytologically documented invasive breast cancer: unresectable, LABC or mBC
4.Prior treatment for breast cancer in the adjuvant, unresectable, locally advanced, or metastatic setting must include:-
i.A taxane, alone or in combination with another agent, AND
ii.Trastuzumab, alone or in combination with another agent in the adjuvant, unresectable, locally advanced, or metastatic setting
5.Documented progression of unresectable, locally advanced, or mBC, determined by the investigator; progression must occur during or after most recent treatment for LABC/mBC or within 6 months after completing adjuvant therapy
6.Measurable and/or non-measurable disease
7.LVEF >= 50% by echocardiogram (ECHO)
8.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
9.Adequate organ function, evidenced by the following laboratory results within 30 days of enrollment:
i.Absolute neutrophil count > 1,500 cells/mm3
ii.Platelet count > 100,000 cells/mm3
iii.Hemoglobin > 9.0 g/dL. Patients will be allowed to be transfused red blood cells to this level
iv.Albumin >= 2.5 g/dL
v.Total bilirubin <= 1.5 upper limit of normal (ULN)
vi.Serum glutamic oxaloacetic transaminase (SGOT) or aspartate aminotransferase (AST), serum glutamic pyruvic transaminase (SGPT) or alanine aminotransferase (ALT), and alkaline phosphatase (ALP) <= 2.5 Ã? ULN with the following exception: Patients with bone metastases: ALP <= 5 Ã? ULN
vii.Creatinine clearance > 50 mL/min based on Cockroft-Gault glomerular filtration rate estimation: (140 â?? Age) Ã? (weight in kg) Ã? (0.85 if female)/(72 Ã? serum creatinine)
viii.International normalized ratio (INR) and activated partial thromboplastin time (aPTT) < 1.5 Ã? ULN (unless on therapeutic coagulation)
10.A negative serum β-Human Chorinic Gonadotropin (β-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) within 7 days prior to the first dose of study treatment with the result available prior to first dosing
11.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 ï?¼ 1% per year, during the treatment period and for at least 7 months after the last dose of study drug
A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (ï?³ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal
1.Prior treatment with trastuzumab emtansine
2.Prior treatment with lapatinib or lapatinib with capecitabine or non-comparable biologic or biosimilar of trastuzumab
3.Peripheral neuropathy of Grade >= 3 per NCI CTCAE (version 4.03)
4.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
5.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
6.History of exposure to the following cumulative doses of anthracyclines:
i.Doxorubicin or liposomal doxorubicin > 500 mg/m2
ii.Epirubicin > 900 mg/m2
iii.Mitoxantrone > 120 mg/m2
iv.If another anthracycline, or more than one anthracycline, has been used, the cumulative dose must not exceed the equivalent of 500 mg/m2 doxorubicin
7.History of radiation therapy within 14 days of enrollment. The patient must have recovered from any resulting acute toxicity (to Grade <= 1) prior to enrollment.
8.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
9.History of a decrease in LVEF to < 40% or symptomatic congestive heart failure (CHF) with previous trastuzumab treatment
10.History of symptomatic chronic heart failure (New York Heart Association [NYHA] Classes IIâ??IV) or serious cardiac arrhythmia requiring treatment
11.History of myocardial infarction or unstable angina within 6 months of enrollment
12.Current dyspnea at rest due to complications of advanced malignancy or requirement for continuous oxygen therapy
13.Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease)
14.Pregnancy or lactation
15.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
16.Presence of conditions that could affect gastrointestinal absorption: malabsorption syndrome, resection of the small bowel or stomach, and ulcerative colitis
17.History of intolerance (such as Grade 3-4 infusion reaction) or known hypersensitivity to trastuzumab or murine proteins or any component of the product
18.Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary outcome measures for this study are on safety evaluationTimepoint: â?¢Incidence and severity of AEs and SAEs as per NCI-CTCAE (version 4.03) <br/ ><br>â?¢Incidence of non-serious AEs of special interest <br/ ><br>â?¢Cases of drug-induced liver injury meeting Hyâ??s law criteria <br/ ><br>â?¢Incidence of CHF <br/ ><br>â?¢Left Ventricular ejection fraction (LVEF) decrease over the course of the study as measured by ECHO <br/ ><br>â?¢Laboratory results abnormalities <br/ ><br>â?¢Incidence of AEs leading to discontinuation, modification, or interruption of study medication <br/ ><br>â?¢Exposure to study medication <br/ ><br>
- Secondary Outcome Measures
Name Time Method The secondary outcome measures for this study are on efficacy evaluationTimepoint: <br/ ><br>â?¢Progression-free survival (assessed by RECISTv1.1) <br/ ><br>â?¢Overall survival (OS) <br/ ><br>â?¢Overall response rate (assessed by RECISTv1.1) <br/ ><br>