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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 neo/adjuvant setting

PHRR121210-000033

Protocol No. EGF114299

2012-CT0008

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 neo/adjuvant setting

This is a Phase III, randomized, open-label, multi-center, three arm study of lapatinib plus trastuzumab plus an aromatase inhibitor (AI), trastuzumab plus an AI, or lapatinib plus an AI to evaluate the efficacy and safety of these regimens as first-line therapy in postmenopausal subjects with hormone receptor positive (HR+), HER2-positive metastatic breast cancer (MBC) who have received trastuzumab and endocrine therapy in the neoadjuvant and/or adjuvant setting. Eligible subjects will be postmenopausal; have tumors that are ER and/or PgR positive and HER2-positive; have newly diagnosed Stage IV metastatic breast cancer; and have not received systemic or local treatment for MBC. The primary objective is to demonstrate superiority of lapatinib/trastuzumab/AI combination versus (vs.) trastuzumab/AI combination for overall survival. The secondary objectives are to evaluate overall survival in trastuzumab/AI vs. lapatinib/AI and trastuzumab/lapatinib/AI vs. lapatinib/AI, progression free survival, overall response rate, clinical benefit rate, the safety and tolerability of all three treatment groups (lapatinib plus trastuzumab plus an AI, trastuzumab plus an AI, or lapatinib plus an AI), and quality of life status relative to baseline.

Start Date Duration in Months Target Completion Date Actual Completion Date
2011-05-02 72 2017-05-02 0000-00-00

Ongoing

Institution Classification Region LTO #
PPD Development (S) PTE. LTD. Private Business NCR
Institution Classification Region LTO #
GlaxoSmithKline USA Private Business United States of America
Institution Amount Region
GlaxoSmithKline USA N/A United States of America
Name E-Mail Phone Number Postal Address
Fridee-May Ortega Fridee-May.Ortega@ppdi.com +632 6896516 9/F Sun Life Centre 5th Avenue Corner Rizal Drive, Bonifacio Global City, Taguig City
Name E-Mail Phone Number Postal Address
US GSK Clinical Trials Call Center GSKClinicalSupportHD@gsk.com 877-379-3718 1250 South Collegeville Road Collegeville, PA 19426, USA
Name Expertise Affiliation
Rubi K. Li, MD Medical Oncologist St. Luke's Medical Center - Quezon City
Project Location Institutional Ethics Review Board
St. Luke's Medical Center - Quezon City St. Luke's Medical Center Institutional Ethics Review Board

Breast Cancer

Overall survival of lapatinib/trastuzumab/aromatase inhibitor (AI) combination vs. trastuzumab/AI combination [ Time Frame: approximately 6 years ]

•Overall survival of trastuzumab/AI vs. lapatinib/AI and trastuzumab/lapatinib/AI vs. lapatinib/AI [ Time Frame: approximately 6 years ] •Progression free survival (PFS) of lapatinib/trastuzumab/AI vs. trastuzumab/AI and lapatinib/AI vs. trastuzumab/AI [ Time Frame: approximately 6 years ] •Overall response rate (complete or partial response), time to response, and duration of response in lapatinib/trastuzumab/AI vs. trastuzumab/AI and lapatinib/AI vs. trastuzumab/AI [ Time Frame: approximately 6 years ] •Clinical benefit (complete response, partial response, or stable disease for at least 6 months) of lapatinib/trastuzumab/AI vs. trastuzumab/AI and lapatinib/AI vs. trastuzumab/AI [ Time Frame: approximately 6 years ] •Safety and tolerability of all three treatment groups (lapatinib/ trastuzumab/ AI, trastuzumab/ AI, or lapatinib/AI) [ Time Frame: approximately 6 years ] •Changes in the quality of life (QoL) status relative to baseline of lapatinib/trastuzumab/AI vs. trastuzumab/AI and lapatinib/AI vs. trastuzumab/AI [ Time Frame: approximately 6 years ] •The identification of tumor-derived biomarkers (DNA, RNA and protein) associated with clinical outcome •The evaluation of biomarkers known to predict sensitivity or resistance to lapatinib and trastuzumab (e.g. p95HER2, PIK3CA mutations, PTEN aberrations and other markers associated with these pathways) and determine the relationship with clinical outcome •The examination of pre and post treatment circulating free DNA (cfDNA) to determine whether mutations (e.g., PI3KCA) in cfDNA correlate with that in the tumor tissue from which it is derived •Dependent on study outcomes, exploratory research may be conducted to identify genetic markers in patient DNA that are associated with response to study drugs.

Recruiting

  • Argentina
  • Belgium
  • Brazil
  • Bulgaria
  • France
  • Germany
  • Greece
  • Hong Kong
  • Hungary
  • India
  • Ireland
  • Israel
  • Italy
  • Japan
  • Lithuania
  • Peru
  • Philippines
  • Poland
  • Portugal
  • Puerto Rico
  • Romania
  • Russia
  • South Korea
  • Spain
  • Taiwan
  • Ukraine
  • United Kingdom
  • United States

Clinical Trial

Unspecified

Unspecified

None

Inclusion Criteria: •Signed written informed consent •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; or 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 •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) •Tumors that are ER+ and/or PgR+ by local laboratory •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] •Subject must have received prior neoadjuvant and/or adjuvant trastuzumab •Subject must have received prior neoadjuvant and/or adjuvant endocrine therapy •Subjects who have a life expectancy of > 6 months as assessed by the treating investigator •Have baseline of Left Ventricular Ejection Fraction (LVEF) >=50% measured by echocardiography (ECHO) or multi-gated acquisition scan (MUGA) •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 •All prior treatment related toxicities must be CTCAE (Version 4.0) <= Grade 1 at the time of randomization •Completion of screening assessments •Adequate baseline organ function defined by baseline laboratory values Exclusion Criteria: •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. •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) •Subjects who received prior chemotherapy, hormonal therapy, immunotherapy, biologic therapy, or anti-HER2 therapy for advanced or metastatic disease •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 •Known history of, or clinical evidence of, central nervous system (CNS) metastases or leptomeningeal carcinomatosis •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) •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) •Have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels •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 •Any prohibited medication as described in the EGF114299 protocol •Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment.

Interventional

Lapatinib

Parallel Assignment

Randomized

Open-label

Unspecified

Parallel

Treatment

Phase III

6

Unspecified

N/A

02 May 2011

Utilization Utilization Info
No records found.

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