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A Study to Compare the Safety and Efficacy of an Aromatase Inhibitor in Combination With Lapatinib, Trastuzumab or Both for the Treatment of Hormone Receptor Positive, HER2+ Metastatic Breast Cancer
This study is currently recruiting participants.
Verified May 2012 by GlaxoSmithKline

First Received on July 1, 2010.   Last Updated on May 17, 2012   History of Changes
Sponsor: GlaxoSmithKline
Information provided by (Responsible Party): GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01160211
  Purpose

A study to compare the safety and efficacy of an aromatase inhibitor in combination with lapatinib, trastuzumab or both for the treatment of hormone receptor positive, HER2+ metastatic breast cancer (MBC).


Condition Intervention Phase
Neoplasms, Breast
Drug: lapatinib
Drug: trastuzumab
Drug: Aromatase inhibitor
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Ph III Trial to Compare Safety and Efficacy of Lapatinib Plus Trastuzumab Plus Aromatase Inhibitor (AI) vs. Trastuzumab Plus AI vs. Lapatinib Plus AI as 1st Line in Postmenopausal Subjects With Hormone Receptor+ HER2+ MBC Who Received Trastuzumab and Endocrine Therapy in Neo- and/or Adjuvant Setting

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Overall survival of lapatinib/trastuzumab/aromatase inhibitor (AI) combination vs. trastuzumab/AI combination [ Time Frame: approximately 6 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival of trastuzumab/AI vs. lapatinib/AI and trastuzumab/lapatinib/AI vs. lapatinib/AI [ Time Frame: approximately 6 years ] [ Designated as safety issue: No ]
  • Progression free survival (PFS) of lapatinib/trastuzumab/AI vs. trastuzumab/AI and lapatinib/AI vs. trastuzumab/AI [ Time Frame: approximately 6 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Safety and tolerability of all three treatment groups (lapatinib/ trastuzumab/ AI, trastuzumab/ AI, or lapatinib/AI) [ Time Frame: approximately 6 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • The identification of tumor-derived biomarkers (DNA, RNA and protein) associated with clinical outcome [ Designated as safety issue: No ]
  • 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 outcom [ Designated as safety issue: No ]
  • 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 [ Designated as safety issue: No ]
  • Dependent on study outcomes, exploratory research may be conducted to identify genetic markers in patient DNA that are associated with response to study drugs. [ Designated as safety issue: No ]

Estimated Enrollment: 525
Study Start Date: May 2011
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lapatinib plus trastuzumab plus aromatase inhibitor Drug: lapatinib
1000 mg by mouth once a day
Drug: trastuzumab
Loading dose of 8 mg/kg IV followed by the maintenance dose of 6 mg/kg IV every 3 weeks
Drug: Aromatase inhibitor
Aromatase inhibitor (either letrozole, anastrozole, or exemestane) of investigator's choice given by mouth once daily
Active Comparator: trastuzmab plus aromatase inhibitor Drug: trastuzumab
Loading dose of 8 mg/kg IV followed by the maintenance dose of 6 mg/kg IV every 3 weeks
Drug: Aromatase inhibitor
Aromatase inhibitor (either letrozole, anastrozole, or exemestane) of investigator's choice given by mouth once daily
Active Comparator: lapatinib plus aromatase inhibitor Drug: Aromatase inhibitor
Aromatase inhibitor (either letrozole, anastrozole, or exemestane) of investigator's choice given by mouth once daily
Drug: lapatinib
1500 mg by mouth once daily

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01160211

Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

  Show 128 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01160211     History of Changes
Other Study ID Numbers: 114299
Study First Received: July 1, 2010
Last Updated: May 17, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
1st line MBC
hormone receptor positive
lapatinib
dual HER2 suppression
trastuzumab
HER2 positive
aromatase inhibitor

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Hormones
Trastuzumab
Lapatinib
Aromatase Inhibitors
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on May 24, 2012