HER2-positive metastatic breast cancer who have received trastuzumab and endocrine therapy in the neoadjuvant and/or adjuvant setting MedDRA version: 19.0 Level: PT Classification code 10065430 Term: HER-2 positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Refer to the authorized prescribing information for lapatinib [TYKERB Package Insert, 2010], trastuzumab [HERCEPTIN Package Insert, 2009], letrozole [FEMARA Package Insert, 2010], anastrozole [ARIMIDEX Package Insert, 2009], and exemestane [AROMASIN Package Insert, 2008] for specific information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the study treatment(s) that may impact subject eligibility. Subjects eligible for enrollment in the study must meet all of the following criteria: 1. Signed written informed consent. In Korea and Japan, subjects who are between =18 and 6 HER2/neu gene copies per nucleus or a FISH, CISH or SISH test ratio (HER2 gene copies to chromosome 17 signals) of =2.0] 6. Subject must have received at least one prior regimen containing trastuzumab in combination with chemotherapy for breast cancer:. •Subject has ONLY received prior trastuzumab in combination with chemotherapy as neoadjuvant and/or adjuvant treatment. OR •Subject has received ONE prior trastuzumab-containing regimen for metastatic disease (and has progressed), and may or may not have received prior trastuzumab in combination with chemotherapy as neoadjuvant and/or adjuvant treatment. 7. Subject must have received prior endocrine therapy (such as aromatase inhibitors or selective estrogen receptor modulators). 8. Subjects who have a life expectancy of > 6 months as assessed by the treating investigator 9. Subjects must have baseline Left Ventricular Ejection Fraction (LVEF) =50% measured by echocardiography (ECHO) or multi-gated acquisition scan (MUGA) 10. Subject must have an ECOG performance status of 0-1 (Section 12.2, Appendix 2) 11. All prior treatment related toxicities must be CTCAE (Version 4.0) = Grade 1[NCI, 2009] at the time of randomization 12. Completion of screening assessments 13. Adequate baseline organ function defined by: (Refer to Protocol page 27) 14. Subjects must meet all of the following criteria: •QTc <450msec or •QTc <480msec for subjects with bundle branch block The QTc is the QT interval corrected for heart rate according to either Bazett’s formula (QTcB) or to Fridericia’s formula (QTcF
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. History of another malignancy. Exception: Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. 2. Subjects with extensive symptomatic visceral disease including hepatic involvement and pulmonary lymphangitic spread of tumor, or the disease is considered by the investigator to be rapidly progressing or life threatening (subjects who are intended for chemotherapy) 3. Serious cardiac illness or medical condition including but not confined to: ? Uncontrolled arrhythmias ? Uncontrolled or symptomatic angina ? History of congestive heart failure (CHF) ? Documented myocardial infarction <6 months from study entry 4. Known history of, or clinical evidence of, central nervous system (CNS) metastases or leptomeningeal carcinomatosis 5. Have acute or currently active/requiring anti-viral therapy hepatic or biliary disease (with the exception of subjects with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) 6. Have a concurrent disease or condition that may interfere with study participation, or any serious medical disorder that would interfere with the subject’s safety (for example, active or uncontrolled infection or any psychiatric condition prohibiting understanding or rendering of informed consent) 7. Have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels 8. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to any of the study agents or their excipients that, in the opinion of the Investigator or GSK medical monitor, contraindicates their participation 9. Any prohibited medication as described in Section 6.2. 10. Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary efficacy endpoint of this study is PFS assessed for lapatinib/trastuzumab/AI combination (Treatment Group A) vs. trastuzumab/AI combination (Treatment Group B). PFS is defined as the time from randomization until disease progression as assessed by the investigator or date of death due to any cause.;Timepoint(s) of evaluation of this end point: The time point of primary end point, overall survival will be assessed at the end of study - Q2 2018;Secondary Objective: • To compare progression free survival (PFS) in Treatment Group B (trastuzumab/AI) vs. Treatment Group C (lapatinib/AI) and Treatment Group A (trastuzumab/lapatinib/AI) vs. Treatment Group C (lapatinib/AI) • To compare overall survival (OS) in Treatment Group A (lapatinib/trastuzumab/AI) vs. Treatment Group B (trastuzumab/AI) and Treatment Group C ( lapatinib/AI) vs. Treatment Group B (trastuzumab/AI) • To compare overall response rate (complete or partial response), time to response, and duration of response in Treatment Group A (lapatinib/trastuzumab/AI) vs. Treatment Group B (trastuzumab/AI) and Treatment Group C (lapatinib/AI) vs. Treatment Group B (trastuzumab/AI) • To compare clinical benefit rate (complete response, partial response, or stable disease for at least 6 months) in Treatment Group A (lapatinib/trastuzumab/AI) vs. Treatment Group B (trastuzumab/AI) and Treatment Group C (lapatinib/AI) vs. Treatment Group B (trastuzumab/AI);Main Objective: The primary objective is to demonstrate superiority of lapatinib/trastuzumab/AI combination (Treatment Group A) vs. trastuzumab/AI combination (Treatment Group B) for progression free survival (PFS). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints of this study are: • PFS in Treatment Group B (trastuzumab/AI) vs. Treatment Group C (lapatinib/AI) and Treatment Group A (trastuzumab/lapatinib/AI) vs. Treatment Group C (lapatinib/AI) defined as the time from randomization and the earlier of date of progression as assessed by the investigator or date of death due to any cause. • OS which is defined as the time from randomization until death due to any cause in Treatment Group A (lapatinib/trastuzumab/AI) vs. Treatment Group B (trastuzumab/AI) and Treatment Group B (trastuzumab/AI) vs. Treatment Group C (lapatinib/AI) as assessed by the investigator. • Overall response rate (complete or partial response) which is defined as the percentage of subjects achieving either a CR or PR as per RECIST 1.1 criteria in Treatment Group A (lapatinib/trastuzumab/AI) vs. Treatment Group B (trastuzumab/AI) and Treatment Group C (lapatinib/AI) vs. Treatment Group B (trastuzumab/AI) as assessed by the investigator. • Time to response which is defined as the time from randomization until first documented evidence of PR or CR (whichever status is recorded first) as per RECIST 1.1 criteria in Treatment Group A (lapatinib/trastuzumab/AI) vs. Treatment Group B (trastuzumab/AI) and Treatment Group C (lapatinib/AI) vs. Treatment Group B (trastuzumab/AI) as assessed by the investigator. • Duration of response which is defined, for the subset of subjects who achieve a CR or PR, to be the time from first documented evidence of PR or CR until the first documented sign of disease progression or death due to breast cancer, if sooner as per RECIST 1.1 criteria in Treatment Group A (lapatinib/trastuzumab/AI) vs. Treatment Group B (trastuzumab/AI) and Treatment Group C (lapatinib/AI) vs. Treatment Group B (trastuzumab/AI) as assessed by the investigator. • Clinical benefit in Treatment Group A (lapatinib/trastuzumab/AI) vs. Treatment Group B (trastuzumab/AI) and Treatment Group C (lapa | — |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, China, Colombia, Croatia, France, Germany, Greece, Hong Kong, Hungary, India, Ireland, Israel, Italy, Japan, Korea, Republic of, Lithuania, Mexico, Norway, Peru, Philippines, Poland, Portugal, Romania, Russian Federation, Serbia, Singapore, Spain, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactGSK Clinical Support Helpdesk
GlaxoSmithKline
Outcome results
None listed