Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Related Information
Registry Information

Alternate Title

Letrozole With or Without Lapatinib in Treating Postmenopausal Women With Stage IV Breast Cancer

Basic Trial Information

Objectives

Primary

1. Compare the time to progression in postmenopausal women with estrogen receptor- and/or progesterone receptor-positive stage IV breast cancer treated with letrozole with or without lapatinib ditosylate.

Secondary

1. Compare the overall response rate in patients treated with these regimens.
2. Compare the clinical benefit of these regimens in these patients.
3. Compare the time to response and duration of response in patients treated with these regimens.
4. Compare the 6-month progression-free survival and overall survival of patients treated with these regimens.
5. Compare the quality of life of patients treated with these regimens.
6. Compare the qualitative and quantitative toxic effects of these regimens in these patients.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed invasive breast cancer, meeting 1 of the following staging criteria:
  • Stage IV

• Tumor tissue available for testing

• No CNS metastases or leptomenigeal carcinomatosis

• Hormone receptor status:
  • Estrogen and/or progesterone receptor-positive

Prior/Concurrent Therapy:

Biologic therapy

• No prior Her1 or Her2/neu inhibitors (e.g., trastuzumab (Herceptin®) or cetuximab) in the metastatic setting
• No prior biologic therapy for advanced or metastatic disease
• No other concurrent biologic therapy
• No concurrent immunotherapy

Chemotherapy

• No prior chemotherapy for advanced or metastatic disease
• No concurrent chemotherapy

Endocrine therapy

• At least 1 month since prior hormone-replacement therapy
• More than 1 year since prior adjuvant therapy with an aromatase inhibitor
• No prior systemic endocrine therapy for advanced or metastatic disease
• No concurrent hormonal therapy except letrozole
• No concurrent oral or intravenous steroids
  • Inhaled steroids allowed

Radiotherapy

• No prior radiotherapy for advanced or metastatic disease
  • Prior palliative radiotherapy allowed to limited area (e.g., painful bone metastases) provided it is not the sole site of disease
• No concurrent radiotherapy

Surgery

• No prior resection of the stomach or small bowel
• No concurrent tumor embolization
• No concurrent surgery

Other

• Recovered from all prior therapy
• More than 30 days or 5 half-lives since prior investigational drugs
• No prior cytotoxic therapy for advanced or metastatic disease
• No other prior therapy for advanced or metastatic disease
• Prior neoadjuvant or adjuvant therapy allowed provided patient has developed newly relapsed advanced or metastatic disease
• No other prior ErbB1 or ErbB2 inhibitors (e.g., gefitinib or erlotinib)
• No other concurrent anticancer therapy
• No other concurrent investigational therapy or clinical trial participation
• No concurrent initiation of bisphosphonates
• No concurrent inducers or inhibitors of CYP3A4, including any of the following:
  • Clarithromycin
  • Erythromycin
  • Troleandomycin
  • Rifampin
  • Rifabutin
  • Delaviridine
  • Indinavir
  • Nelfinavir
  • Ritonavir
  • Saquinavir
  • Efavirenz
  • Nevirapine
  • Amprenavir
  • Lopinavir
  • Phenytoin
  • Carbamazepine
  • Phenobarbital
  • Nefazodone
  • Fluvoxamine
  • Itraconazole
  • Ketoconazole
  • Fluconazole (> 150 mg/day)
  • Voriconazole
  • Antacids (within 1 hour before and after study drug)
  • Cimetidine
  • Glucocoticoids
  • Amiodirone
  • Diltiazem
  • Hypericum perforatum (St. John's wort)
  • Grapefruit or grapefruit juice
  • Rifabutin
  • Mibefradil
  • Diethyldithiocarbamate
  • Gestodene
  • Mifepristone
  • Modafinil

Patient Characteristics:

Age

• 18 and over

Sex

• Female

Menopausal status

• Postmenopausal, defined by any of the following:
  • At least 60 years of age
  • Under 60 years of age AND amenorrheic for ≥ 12 months AND/OR follicle-stimulation hormone values within postmenopausal range
  • Prior bilateral oophorectomy OR prior radiation castration with amenorrhea for ≥ 6 months

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL (transfusions allowed)

Hepatic

• Albumin ≥ 2.5 g/dL
• Bilirubin ≤ 1.5 times upper limit of normal (ULN) (unless due to Gilbert's syndrome)
• AST and ALT ≤ 3 times ULN (≤ 5 times ULN if due to liver metastases)

Renal

• Creatinine ≤ 1.5 times ULN

  OR

• Creatinine clearance ≥ 40 mL/min

Cardiovascular

• Ejection fraction normal by echocardiogram
• No uncontrolled or symptomatic angina
• No uncontrolled or symptomatic arrhythmias
• No congestive heart failure
• No other uncontrolled or symptomatic cardiac conditions

Gastrointestinal

• No malabsorption syndrome
• No disease significantly affecting gastrointestinal function
• No ulcerative colitis

Immunologic

• No active or uncontrolled infection
• No known immediate or delayed hypersensitivity reaction or indiosyncrasy to drugs chemically related to study agents or their excipients
• No known hypersensitivity to letrozole or its excipients

Other

• Not pregnant or nursing
• Able to swallow and retain oral medication
• No unresolved or unstable serious toxicity
• No dementia, altered mental status, or psychiatric condition that would preclude giving informed consent
• No other disease or condition that would preclude study participation
• No other malignancy within the past 5 years except completely resected nonmelanoma skin cancer or successfully treated carcinoma in situ

Expected Enrollment

A total of 1280 patients will be accrued for this study.

Outcomes

Time to progression

Overall tumor response rate
Clinical benefit
Time to response
Duration of response
Progression-free survival at 6 months
Overall survival

Outline

This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to site of disease (soft tissue/visceral disease vs bone-only disease) and prior adjuvant antiestrogen therapy (< 6 months from discontinuation vs ≥ 6 months from discontinuation OR no prior antiestrogen therapy). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral lapatinib ditosylate and oral letrozole once daily.

• Arm II: Patients receive oral placebo and oral letrozole once daily.

Treatment in both arms continues in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, every 12 weeks during therapy, and upon discontinuation of therapy.

Patients are followed for survival.

Sherrill B, Amonkar MM, Sherif B, et al.: Quality of life in hormone receptor-positive HER-2+ metastatic breast cancer patients during treatment with letrozole alone or in combination with lapatinib. Oncologist 15 (9): 944-53, 2010.[PUBMED Abstract]

Johnston S, Pippen J Jr, Pivot X, et al.: Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol 27 (33): 5538-46, 2009.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

GlaxoSmithKline

Acurian Pre-Screening Evaluation Contact		Ph: 800-563-6537

U.S.A.
Arizona
	Tucson
	Arizona Clinical Research Center, Incorporated
		Manuel Modiano, MD	Ph:  800-563-6643
Arkansas
	Hot Springs
	Genesis Cancer Center
		R. Timothy Webb, MD	Ph:  800-563-6643
	Jonesboro
	NEA Medical Clinic - East Matthews
		Ronald Blachly, MD	Ph:  800-563-6643
			Email: d_smith@neaclinic.com
California
	Alhambra
	Central Hematology Oncology Medical Group, Incorporated - Alhambra
		Eddie Hu, MD	Ph:  800-563-6643
	Bakersfield
	Comprehensive Blood and Cancer Center
		Ravindranath Patel, MD	Ph:  800-563-6643
	Concord
	East Bay Medical Oncology Hematology Associates - Concord
		Ostap Melnyk, MD	Ph:  800-563-6643
	Fountain Valley
	Compassionate Cancer Care Medical Group Incorporated - Fountain Valley
		Haresh Jhangiani, MD	Ph:  800-563-6643
			Email: hjhangiani@yahoo.com
	Fresno
	California Oncology of the Central Valley
		Christopher Perkins, MD	Ph:  800-563-6643
	Fullerton
	Virginia K. Crosson Cancer Center at St. Jude Medical Center
		Richard Lloyd, MD	Ph:  800-563-6643
	La Jolla
	Rebecca and John Moores UCSD Cancer Center
		Barbara Anne Parker, MD	Ph:  800-563-6643
	Long Beach
	Pacific Shores Medical Group - Long Beach
		Andre Liem, MD	Ph:  800-563-6643
	Los Angeles
	Jonsson Comprehensive Cancer Center at UCLA
		David Reese	Ph:  800-563-6643
		Mark Pegram, MD	Ph:  800-563-6643
	Kenmar Research Institute
		Eduardo Lim, MD	Ph:  800-563-6643
	Northridge
	North Valley Hematology-Oncology Medical Group
		Sheldon Davidson, MD, FACP	Ph:  800-563-6643
			Email: sheljdavid@aol.com
	Oxnard
	Ventura Hematology-Oncology Specialists - Oxnard
		Rosemary McIntyre, MD	Ph:  800-563-6643
	Pomona
	Wilshire Oncology Medical Group, Incorporated - Pomona
		Linda Bosserman, MD, FACP	Ph:  800-563-6643
			Email: linda.bosserman@womgi.com
	Poterville
	Sierra View District Hospital
		Deepika Wali, MD	Ph:  800-563-6643
	Redondo Beach
	Cancer Care Associates Medical Group - Redondo Beach
		David Chan, MD	Ph:  800-563-6643
	San Diego
	Kaiser Permanente Medical Center - Kaiser Foundation Hospital - San Diego
		Jonathan Polikoff, MD	Ph:  800-563-6643
	Santa Barbara
	Sansum Medical Clinic
		Julie Taguchi, MD	Ph:  800-563-6643
			Email: jtaguchi@sansumclinic.org
	Solvang
	Santa Barbara Hematology Oncology - Solvang
		Frederic Kass, MD	Ph:  800-563-6643
	Vallejo
	Kaiser Permanente Medical Center - Vallejo
		Louis Fehrenbacher, MD	Ph:  800-563-6643
	Vista
	San Diego Cancer Center - Vista
		Mark Adler, MD	Ph:  800-563-6643
			Email: mja@sdcri.org
Colorado
	Aurora
	Rocky Mountain Cancer Centers - Aurora
		Sami Diab, MD	Ph:  800-563-6643
	University of Colorado Cancer Center at UC Health Sciences Center
		Anthony Elias, MD	Ph:  800-563-6643
			Email: Anthony.Elias@uchsc.edu
	Longmont
	Rocky Mountain Cancer Centers - Longmont
		Robert Fisher, MD	Ph:  800-563-6643
			Email: rljrfisher@aol.com
	Wheat Ridge
		Jennifer Caskey, MD	Ph:  303-467-3490 800-563-6643
Connecticut
	Hartford
	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
		Susan Rabinowe, MD	Ph:  800-563-6643
Florida
	Boca Raton
	Center for Hematology-Oncology - Boca Raton
		Jane Skelton, MD	Ph:  800-563-6643
	Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus
		Israel Wiznitzer, MD	Ph:  800-563-6643
			Email: iwiznitzer@lrccw.com
	Gainesville
		Robert R. Carroll, MD	Ph:  352-331-2777 800-563-6643
	University of Florida Shands Cancer Center
		Contact Person	Ph:  352-273-8010
	Lakeland
	Center for Cancer Care and Research at Watson Clinic, LLP
		Ruben Saez, MD	Ph:  800-563-6643
			Email: rsaez@watsonclinic.com
	Lakeland Regional Cancer Center at Lakeland Regional Medical Center
		James Jakub	Ph:  800-563-6643
			Email: jim.jakub@lrmc.com
	Miami
	University of Miami Sylvester Comprehensive Cancer Center - Miami
		Stefan Gluck, MD, PhD, FRCPC	Ph:  800-563-6643
			Email: sgluck@med.miami.edu
	Orlando
	Florida Hospital Cancer Institute
		Rebecca Moroose, MD	Ph:  800-563-6643
			Email: rebecca.moroosemd@flhosp.org
	Plantation
	Cancer Research Network, Incorporated
		Elizabeth Tan-Chiu	Ph:  800-563-6643
	Port Saint Lucie
	Hematology Oncology Associates of the Treasure Coast - Port St. Lucie
		Nicholas Iannotti, MD	Ph:  800-563-6643
	West Palm Beach
	Palm Beach Cancer Institute - West Palm Beach
		Elisabeth McKeen, MD	Ph:  800-563-6643
			Email: elisabeth.mckeen@pbcancer.com
Georgia
	Marietta
	Northwest Georgia Oncology Centers, PC - Marietta Center
		Hillary Hahm, MD, PhD	Ph:  800-563-6643
			Email: hhahm@ngoc.com
	Tucker
	Georgia Cancer Specialists - Tucker
		Mansoor Saleh, MD	Ph:  800-563-6643
Illinois
	Peoria
	Oncology Hematology Associates of Central Illinois, PC - Peoria
		Sachdev Thomas, MD	Ph:  800-563-6643
			Email: sthomas@ohaci.com
	Skokie
	Hematology/Oncology of the North Shore at Gross Point Medical Center
		Edward Kaplan, MD	Ph:  800-563-6643
			Email: ekap@dnamail.com
Iowa
	Bettendorf
	Hematology Oncology Associates of the Quad Cities
		Shobha Chitneni, MD, MBBS	Ph:  800-563-6643
Kentucky
	Louisville
	James Graham Brown Cancer Center at University of Louisville
		Damian Laber, MD, FACP	Ph:  800-563-6643
			Email: damianla@ulh.org
Louisiana
	Metairie
		Jayne Gurtler, MD, FACP	Ph:  504-885-0577 800-563-6643
	New Orleans
	Ochsner Cancer Institute at Ochsner Clinic Foundation
		Carl Kardinal, MD	Ph:  800-563-6643
			Email: ckardinal@ochsner.org
Maryland
	Annapolis
	Annapolis Oncology Center
		Kevin Knopf, MD	Ph:  800-563-6643
			Email: kbk@annapolisoncology.org
Massachusetts
	Worcester
	Fallon Clinic at Worcester Medical Center
		Christopher Seidler, MD	Ph:  800-563-6643
			Email: christopher.seidler@fallon-clinic.com
Michigan
	Royal Oak
	Cancer Care Associates - Royal Oak
		Anthony D'Errico, DO	Ph:  800-563-6643
Minnesota
	Duluth
	St. Luke's Hospital Cancer Care Center
		Tanya Repka, MD, FACP	Ph:  800-563-6643
	Minneapolis
	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
		Daniel Schneider, MD	Ph:  800-563-6643
			Email: daniel.j.schneider@healthpartners.com
	Robbinsdale
	Humphrey Cancer Center at North Memorial Outpatient Center
		Gauri Nagargoje	Ph:  800-563-6643
	St. Louis Park
	CCOP - Metro-Minnesota
		Patrick Flynn, MD	Ph:  800-563-6643
			Email: patrick.flynn@usoncology.com
Missouri
	Saint Louis
	Center for Cancer Care and Research
		Alfred Greco, MD	Ph:  800-563-6643
			Email: AGreco@tcccr.com
	David C. Pratt Cancer Center at St. John's Mercy
		Bethany Sleckman, MD	Ph:  800-563-6643
	St. Charles
	Missouri Cancer Care, PC at St. Joseph Health Center - St. Charles
		Timothy Pluard, MD	Ph:  800-563-6643
Nebraska
	Omaha
	Methodist Estabrook Cancer Center
		Robert Langdon, MD	Ph:  800-563-6643
Nevada
	Las Vegas
	Comprehensive Cancer Centers of Nevada - Central Valley
		Heather Allen, MD	Ph:  800-563-6643
			Email: heather.allen@usoncology.com
New Jersey
	Voorhees
	Cancer Institute of New Jersey at Cooper - Voorhees
		Generosa Grana, MD	Ph:  800-563-6643
			Email: grana-generosa@cooperhealth.edu
New Mexico
	Santa Fe
	New Mexico Cancer Care Associates
		Timothy Lopez, MD	Ph:  800-563-6643
			Email: timothy.lopez@nmcancercare.com
New York
	Manhasset
	Don Monti Comprehensive Cancer Center at North Shore University Hospital
		Daniel Budman, MD	Ph:  800-563-6643
	Rochester
	Interlakes Oncology/Hematology PC
		Jonathan Rubins, MD	Ph:  800-563-6643
North Carolina
	Chapel Hill
	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
		Frances Collichio, MD	Ph:  800-563-6643
			Email: fcollich@med.unc.edu
	Durham
	Duke Cancer Institute
		Kaushik Sen, MD	Ph:  800-563-6643
	Greenville
	Physicians East, PA - Quadrangle
		Jesse Lee, MD	Ph:  800-563-6643
Ohio
	Canton
	Gabrail Cancer Center - Canton Office
		Nashat Gabrail, MD	Ph:  800-563-6643
			Email: ngabrailmd@aol.com
Pennsylvania
	Hershey
	Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
		Allan Lipton, MD	Ph:  800-563-6643
			Email: alipton@psu.edu
	Philadelphia
	Fox Chase Cancer Center - Philadelphia
		Lori Goldstein, MD	Ph:  800-563-6643
			Email: lj_goldstein@fccc.edu
	Pittsburgh
	Allegheny Cancer Center at Allegheny General Hospital
		Charles Geyer, FACP, MD	Ph:  800-563-6643
South Carolina
	West Columbia
	South Carolina Oncology Associates, PA
		Rosemary Lambert-Falls, MD	Ph:  800-563-6643
Tennessee
	Knoxville
	Thompson Cancer Survival Center
		Samuel McCachren, MD	Ph:  800-563-6643
	Memphis
	West Clinic - East Memphis
		Lee Schwartzberg, MD	Ph:  800-563-6643
			Email: lschwartzberg@westclinic.com
Texas
	Amarillo
	Harrington Cancer Center
		Brian Pruitt, MD	Ph:  800-563-6643
	Dallas
	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
		Debasish Tripathy, MD	Ph:  800-563-6643
	Irving
	Texas Oncology, PA - Irving
		Gerald Edelman, MD, PhD	Ph:  800-563-6643
			Email: gerald.edelman@usoncology.com
Utah
	Ogden
	Utah Hematology Oncology, PC
		Vincent Hansen, MD	Ph:  800-563-6643
	Salt Lake City
	Utah Cancer Specialists - Administrative Office
		W. Harker, MD	Ph:  800-563-6643
Vermont
	Burlington
	Fletcher Allen Health Care - Medical Center Campus
		Julie Olin, MD	Ph:  800-563-6643
Virginia
	Danville
	Danville Hematology and Oncology, Incorporated
		Timothy Brotherton, PhD, MD	Ph:  800-563-6643
			Email: dhodata@hotmail.com
	Mechanicsville
	Virginia Cancer Institute - Atlee Medical Park
		Maura Hagan, MD	Ph:  800-563-6643
Washington
	Seattle
	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
		Kristine Rinn	Ph:  800-563-6643
	Tacoma
	Northwest Medical Specialties, PLLC - Tacoma
		Francis Senecal, MD	Ph:  800-563-6643
			Email: fmsenecal@hotmail.com
West Virginia
	Charleston
	David Lee Outpatient Cancer Center at Charleston Area Medical Center
		Steven Jubelirer, MD	Ph:  800-563-6643

Related Information

Website for additional information.

Registry Information
Official Title		Study Comparing GW572016 and Letrozole Versus Letrozole in Subjects with Advanced or Metastatic Breast Cancer
Registered in ClinicalTrials.gov		NCT00073528
Date Submitted to PDQ		2004-04-14
Information Last Verified		2007-10-18

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