A Phase III trial to compare the safety and efficacy of lapatinib plus trastuzumab plus an aromatase inhibitor (AI) versus trastuzumab plus an AI versus lapatinib plus an AI as first-line therapy in postmenopausal subjects with hormone receptor positive, HER2-positive metastatic breast cancer (MBC) who have received trastuzumab and endocrine therapy in the neoadjuvant and/or adjuvant setting.

GLAXOSMITHKLINE RESEARCH & DEVELOPMENT LTD.0 sites525 target enrollmentMarch 8, 2012

DrugsTyverb Herceptin

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Not specified
Sponsor: GLAXOSMITHKLINE RESEARCH & DEVELOPMENT LTD.
Enrollment: 525
Status: Active, not recruiting
Last Updated: 9 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

March 8, 2012

End Date

TBD

Last Updated

9 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

Female

Investigators

Sponsor

GLAXOSMITHKLINE RESEARCH & DEVELOPMENT LTD.

Eligibility Criteria

Inclusion Criteria

•Subjects eligible for enrollment in the study must meet all of the following criteria: 1\. Signed written informed consent 2\. Post\-menopausal female subjects \=18 years of age. Post\-menopausal as defined by any of the following: • Age \> 60 years • Age \= 45 years with amenorrhea \> 12 months with an intact uterus • Having undergone a bilateral oophorectomy or radiation castration with amenorrhea for at least 6 months • FSH and estradiol levels in postmenopausal range (utilizing ranges from the local laboratory facility). In subjects who have previously been treated with an GnRH/LHRH analogue, the last injection must have been administered \>4 months prior to randomization and menses must not have restarted 3\. Histologically confirmed Stage IV invasive breast cancer • Subjects may have either measurable or non\-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST 1\.1\) \[Eisenhauer, 2009] 4\. Tumors that are ER\+ and/or PgR\+ by local laboratory 5\. Documentation of HER2 overexpression or gene amplification, in the invasive component of either the primary tumor or metastatic disease site as defined as: • 3\+ by Immunohistochemistry (IHC) and/or • HER2/neu gene amplification by fluorescence, chromogenic or silver in situ hybridization \[FISH, CISH or SISH; \>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 prior neoadjuvant and/or adjuvant trastuzumab 7\. Subject must have received prior neoadjuvant and/or adjuvant endocrine therapy 8\. Subjects who have a life expectancy of \> 6 months as assessed by the treating investigator 9\. Have baseline of Left Ventricular Ejection Fraction (LVEF) \=50% measured by echocardiography (ECHO) or multi\-gated acquisition scan (MUGA) 10\. 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 page 26 of Protocol)
•Are the trial subjects under 18? no
•Number of subjects for this age range: 0
•F.1\.2 Adults (18\-64 years) yes
•F.1\.2\.1 Number of subjects for this age range 340
•F.1\.3 Elderly (\>\=65 years) yes
•F.1\.3\.1 Number of subjects for this age range 185

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\. Subjects who received prior chemotherapy, hormonal therapy, immunotherapy, biologic therapy, or anti\-HER2 therapy for advanced or metastatic disease 4\. 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 5\. Known history of, or clinical evidence of, central nervous system (CNS) metastases or leptomeningeal carcinomatosis 6\. Current active hepatic or biliary disease (with exception of subjects with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) 7\. 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) 8\. Have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels 9\. 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 10\. Any prohibited medication as described in Section 6\.2 of the protocol. 11\. Administration of an investigational drug within 30 days or 5 halflives, whichever is longer, preceding the first dose of study treatment.