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

Alternate Title

Letrozole in Treating Postmenopausal Women Who Have Received Hormone Therapy for Hormone Receptor-Positive Breast Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active Any age (postmenopausal) NCI NSABP-B-42 NSABP-B-42, NCT00382070

Special Category: CTSU trial

Objectives

Primary

1. Determine whether or not prolonged adjuvant hormonal therapy comprising letrozole vs placebo will improve disease-free interval of postmenopausal women with estrogen receptor-positive and/or progesterone receptor-positive breast cancer who have completed 5 years of hormonal therapy with 5 years of an aromatase inhibitor (AI) or 5 years of a combination of up to 3 years of tamoxifen citrate followed by an AI.
2. Compare the disease-free survival of patients treated with these regimens.

Secondary

1. Compare overall survival of patients treated with these regimens.
2. Compare breast cancer-free survival of patients treated with these regimens.
3. Compare distant recurrence in patients treated with these regimens.
4. Compare the incidence of osteoporotic-related fractures (e.g., Colles', hip, and spine) in these patients treated with these regimens.
5. Compare the incidence of arterial thrombotic events in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically confirmed invasive carcinoma of the breast by core needle or open biopsy
  • Clinical stage I, II, or IIIA primary tumor for patients who received neoadjuvant chemotherapy
  • Primary tumor t1-3 on pathologic evaluation and ipsilateral nodes pN0, pN1 (pN1mi, pN1a, pN1b, pN1c), pN2a, pN3a, or pN3b for patients who received adjuvant chemotherapy



• Received adjuvant hormonal therapy after breast cancer diagnosis for a duration of 57-63 months from the first dose (regardless of the number of missed doses) with 1 of the following:
  • Aromatase inhibitor* (AI)
  • Combination of up to 3 years of tamoxifen citrate followed by an AI for a total of 5 years
    • No tamoxifen citrate during years 4 and 5 of 5-year adjuvant hormonal therapy

   [Note: *Adjuvant AI therapy must be discontinued at the time of randomization]




• Must have completed adjuvant hormonal therapy within the past 6 months



• Must have undergone a bilateral mammogram within the past year (unilateral if patient had a mastectomy)
  • Mammogram not required if patient has a prophylactic contralateral mastectomy



• Must have undergone a bone mineral density test within the past year



• Must have undergone a lumpectomy with axillary nodal staging followed by breast radiotherapy OR a total mastectomy with axillary nodal staging
  • Nodal staging with sentinel node biopsy alone is allowed provided sentinel nodes were negative on H&E staining



• No evidence of recurrent breast cancer by history and physical within the past 3 months



• No diagnosis of bilateral breast cancer, including ductal carcinoma in situ (synchronous or metachronous)



• Estrogen receptor (ER)-positive and/or progesterone receptor-positive tumor
  • Patients with a tumor considered to be borderline hormone receptor-positive that was treated with tamoxifen citrate and/or AI are allowed

Prior/Concurrent Therapy:

• See Disease Characteristics
• No other investigational agent within the past 30 days
• No other concurrent anticancer therapy
• No concurrent participation in any other hormonal therapy or placebo-controlled supportive therapy clinical trial
• No other concurrent hormonal therapy, including any of the following:
  • Hormonal agent for management of osteoporosis (e.g., raloxifene)
  • Selective estrogen receptor modulators (e.g., raloxifene)
  • Sex hormonal therapy (e.g., estrogen- or progesterone-replacement therapy, including low-dose estrogen in the form of vaginal cream) or oral contraceptives
  • Luteinizing hormone-releasing hormone agonists/antagonists (e.g., goserelin)
  • Estradiol acetate
    • Conjugated estrogen ring or estradiol hemihydrate vaginal tab allowed
  • Other aromatase inhibitors
• Concurrent bisphosphonates allowed provided dose is as recommended for bone protection, not anticancer therapy

Patient Characteristics:

• Female
• Postmenopausal as defined by any of the following criteria:
  • Age ≥ 56 years with no spontaneous menses for ≥ 12 months prior to study entry
  • Age ≤ 55 years with no spontaneous menses for ≥ 12 months prior to study entry (e.g., spontaneous or secondary to hysterectomy) AND a documented estradiol level in the postmenopausal range
  • Prior documented bilateral oophorectomy
• ECOG performance status 0 or 1
• Cholesterol ≤ grade 1 (with or without cholesterol-lowering therapy) meeting 1 of the following criteria:
  • Criteria must be met within the past year if patient has any of the following:
    • History of hypercholesterolemia controlled with cholesterol-lowering therapy and/or therapeutic lifestyle changes
    • History of ≥ 1 of the following risk factors for cardiovascular events:
      • Diabetes
      • Hypertension
      • Obesity
      • Tobacco use
      • Hypertriglyceridemia
      • Documented coronary artery disease
      • Family history of premature coronary heart disease
  • Criteria must be met within the past 2 years for all other patients
• Not pregnant or nursing
• Negative pregnancy test
• No history of nontraumatic osteoporotic fracture of the wrist, hip, or spine
• No other malignancies unless disease-free for ≥ 5 years and, in the opinion of the investigator, at low risk for recurrence
• No other prior malignancy within the past 5 years except for the following:
  • Carcinoma in situ of the cervix
  • Colon carcinoma in situ
  • Melanoma in situ
  • Basal cell or squamous cell carcinoma of the skin

Expected Enrollment

A total of 3,840 patients will be accrued for this study.

Outcomes

Disease-free survival

Overall survival
Breast cancer-free interval (time to recurrence or contralateral second primary breast cancer)
Distant recurrence
Incidence of osteoporotic-related fractures (e.g., Colles', hip, and spine)
Incidence of arterial thrombotic events (CTCAE v. 3.0 grades 3, 4, or 5 cardiac ischemia/infarction, CNS cerebrovascular ischemia, peripheral arterial ischemia, and visceral arterial ischemia [nonmyocardial])

Outline

This is a double-blind, multicenter, placebo-controlled, randomized study. Patients are stratified according to pathologic nodal status (negative vs positive), adjuvant tamoxifen citrate therapy (yes vs no), and lowest bone mineral density T score for lumbosacral spine, total hip, or femoral neck (> -2.0 vs ≤ -2.0 standard deviation). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral letrozole once daily.



• Arm II: Patients receive oral placebo once daily.

In both arms, treatment continues for up to 5 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed annually.

Mamounas EP, Lembersky B, Jeong JH, et al.: NSABP B-42: a clinical trial to determine the efficacy of five years of letrozole compared with placebo in patients completing five years of hormonal therapy consisting of an aromatase inhibitor (AI) or tamoxifen followed by an AI in prolonging disease-free survival in postmenopausal women with hormone receptor-positive breast cancer. Clin Breast Cancer 7 (5): 416-21, 2006.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

National Surgical Adjuvant Breast and Bowel Project

Terry Mamounas, MD, MPH, FACS, Protocol chair		Ph: 330-438-6281 Email: tmamounas@aultman.com

U.S.A.
Alabama
	Huntsville
	Clearview Cancer Institute
		Clinical Trials Office - Clearview Cancer Institute	Ph:  256-705-4224
	Mobile
	Providence Cancer Center at Providence Hospital
		Paul Schwarzenberger, MD	Ph:  251-435-5892
Alaska
	Anchorage
	Providence Cancer Center
		Clinical Trials Office - Providence Cancer Center	Ph:  907-261-3109
	Fairbanks
	Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital
		Jacqueline Vuky	Ph:  907-458-5380 800-678-5458
Arkansas
	Little Rock
	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
		Clinical Trial Office - Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Ph:  501-686-8274
California
	Berkeley
	Alta Bates Summit Comprehensive Cancer Center
		Clinical Trials Office - Alta Bates Summit Comprehensive Cancer Center	Ph:  510-204-3428
	Burbank
	Providence Saint Joseph Medical Center - Burbank
		Clinical Trials Office - Providence Saint Joseph Medical Center - Burbank	Ph:  818-847-3220
	Burlingame
	Peninsula Medical Center
		David Irwin, MD	Ph:  510-204-2866
	Castro Valley
	East Bay Radiation Oncology Center
		James Feusner, MD	Ph:  510-428-3689
	Eden Medical Center
		James Feusner, MD	Ph:  510-428-3689
	Valley Medical Oncology Consultants - Castro Valley
		James Feusner, MD	Ph:  510-428-3689
	Duarte
	City of Hope Comprehensive Cancer Center
		Clinical Trials Office - City of Hope Comprehensive Cancer Center	Ph:  800-826-4673
			Email: becomingapatient@coh.org
	Fairfield
	North Bay Cancer Center
		Clinical Trials Office - North Bay Cancer Center	Ph:  707-429-6976
	Fremont
	Kaiser Permanente - Fremont
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Valley Medical Oncology
		James Feusner, MD	Ph:  510-428-3689
	Washington Township Hospital
		Byron Wilson, MD	Ph:  510-797-1111
	Fresno
	Cancer Care Associates
		Charles Kuzma	Ph:  559-326-1222 877-490-4222
	Glendale
	Glendale Memorial Hospital Comprehensive Cancer Center
		Clinical Trials Office - Glendale Memorial Hospital Comprehensive Cancer Center	Ph:  818-409-7653
	Greenbrae
	California Cancer Care, Incorporated - Greenbrae
		Peter Eisenberg, MD	Ph:  415-925-5000
	Marin Cancer Institute at Marin General Hospital
		David Irwin, MD	Ph:  510-204-2866
	Sutter Health - Western Division Cancer Research Group
		David Irwin, MD	Ph:  510-204-2866
	Hayward
	Kaiser Permanente Medical Center - Hayward
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	La Jolla
	Rebecca and John Moores UCSD Cancer Center
		Clinical Trials Office - Rebecca and John Moores UCSD Cancer Center	Ph:  858-822-5354
			Email: cancercto@ucsd.edu
	Scripps Cancer Center - San Diego
		Joan Kroener, MD	Ph:  858-587-4325
	Loma Linda
	Loma Linda University Cancer Institute at Loma Linda University Medical Center
		Clinical Trials Office - Loma Linda University Cancer Institute	Ph:  909-558-3375
	Long Beach
	Pacific Shores Medical Group - Long Beach
		N. Simon Tchekmedyian, MD, FACP	Ph:  562-590-0345
	Los Angeles
	Jonsson Comprehensive Cancer Center at UCLA
		Clinical Trials Office - Jonsson Comprehensive Cancer Center at UCLA	Ph:  888-798-0719
	USC/Norris Comprehensive Cancer Center and Hospital
		Clinical Trials Office - USC/Norris Comprehensive Cancer Center and Hospital	Ph:  323-865-0451
	Mountain View
	El Camino Hospital Cancer Center
		Clinical Trials Office - El Camino Hospital Cancer Center	Ph:  650-988-7623
	Oakland
	Alta Bates Summit Medical Center - Summit Campus
		Clinical Trials Office - Alta Bates Summit Medical Center - Summit Campus	Ph:  510-204-1414
	Bay Area Breast Surgeons, Incorporated
		James Feusner, MD	Ph:  510-428-3689
	CCOP - Bay Area Tumor Institute
		James Feusner, MD	Ph:  510-428-3689
	Highland General Hospital
		James Feusner, MD	Ph:  510-428-3689
	Kaiser Permanente Medical Center - Oakland
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Larry G Strieff MD Medical Corporation
		James Feusner, MD	Ph:  510-428-3689
	Tom K Lee, Incorporated
		James Feusner, MD	Ph:  510-428-3689
	Orange
	Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
		Clinical Trials Office - Chao Family Comprehensive Cancer Center	Ph:  877-UC-STUDY
			Email: ucstudy@uci.edu
	St. Joseph Hospital Regional Cancer Center - Orange
		David Margileth	Ph:  714-771-8999
	Palm Springs
	Desert Regional Medical Center Comprehensive Cancer Center
		Clinical Trials Office - Desert Regional Medical Center Comprehensive Cancer Center	Ph:  760-416-4730
	Pleasanton
	Valley Care Medical Center
		James Feusner, MD	Ph:  510-428-3689
	Valley Medical Oncology Consultants - Pleasanton
		James Feusner, MD	Ph:  510-428-3689
	Pomona
	Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center
		Clinical Trials Office - Robert and Beverly Lewis Family Cancer Care Center	Ph:  909-865-9555
	Rancho Mirage
	Lucy Curci Cancer Center at Eisenhower Memorial Hospital and Medical Center
		Murthy Andavolu	Ph:  760-674-3600
	Redding
	North Valley Breast Clinic
		Lily Lai, MD	Ph:  530-243-5551
	Redwood City
	Kaiser Permanente Medical Center - Redwood City
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Richmond
	Kaiser Permanente Medical Center - Richmond
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Roseville
	Kaiser Permanente Medical Center - Roseville
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Sacramento
	Kaiser Permanente Medical Center - Sacramento
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	South Sacramento Kaiser-Permanente Medical Center
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Sutter Cancer Center
		Clinical Trial Office - Sutter Cancer Center	Ph:  916-454-6595
	San Diego
	Kaiser Permanente Medical Office -Vandever Medical Office
		Jonathan Polikoff, MD	Ph:  619-528-2596
	San Francisco
	California Pacific Medical Center - California Campus
		David Irwin, MD	Ph:  510-204-2866
	Kaiser Permanente Medical Center - San Francisco Geary Campus
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	San Francisco General Hospital Medical Center
		Judith Luce, MD	Ph:  415-206-8000
	San Jose
	Kaiser Permanente Medical Center - Santa Teresa
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	San Pablo
	Doctors Medical Center - San Pablo Campus
		James Feusner, MD	Ph:  510-428-3689
	San Rafael
	Kaiser Foundation Hospital - San Rafael
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Sana Rosa
	CCOP - Santa Rosa Memorial Hospital
		Ian Anderson, MD	Ph:  707-521-3830
	Santa Clara
	Kaiser Permanente Medical Center - Santa Clara Kiely Campus
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Santa Rosa
	Kaiser Permanente Medical Center - Santa Rosa
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	South San Francisco
	Kaiser Permanente Medical Center - South San Francisco
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Stanford
	Stanford Cancer Center
		Clinical Trials Office - Stanford Cancer Center	Ph:  650-498-7061
			Email: cctoffice@stanford.edu
	Stockton
	Kaiser Permanente Medical Facility - Stockton
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Vallejo
	Kaiser Permanente Medical Center - Vallejo
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Sutter Solano Medical Center
		David Irwin, MD	Ph:  510-204-2866
	Walnut Creek
	Kaiser Permanente Medical Center - Walnut Creek
		Louis Fehrenbacher, MD	Ph:  707-651-2577
Colorado
	Aurora
	Aurora Presbyterian Hospital
		Eduardo Pajon, MD	Ph:  303-777-2663
	University of Colorado Cancer Center at UC Health Sciences Center
		Clinical Trials Office - University of Colorado Cancer Center	Ph:  720-848-0650
	Boulder
	Boulder Community Hospital
		Clinical Trials Office - Boulder Community Hospital	Ph:  303-938-5253
	Colorado Springs
	Memorial Hospital Cancer Center - Colorado Springs
		Clinical Trials Office - Memorial Hospital	Ph:  719-365-2406
	Penrose Cancer Center at Penrose Hospital
		Clinical Trials Office - Penrose Cancer Center	Ph:  719-776-5275
	Denver
	CCOP - Colorado Cancer Research Program
		Eduardo Pajon, MD	Ph:  303-777-2663
	Porter Adventist Hospital
		Eduardo Pajon, MD	Ph:  303-777-2663
	Presbyterian - St. Luke's Medical Center
		Clinical Trials Office - Presbyterian - St. Luke's Medical Center	Ph:  303-839-6000
	Rose Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	St. Anthony Central Hospital
		Eduardo Pajon, MD	Ph:  303-777-2663
	St. Joseph Hospital
		Eduardo Pajon, MD	Ph:  303-777-2663
	Englewood
	Swedish Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	Fort Collins
	Front Range Cancer Specialists
		Diana Medgyesy, MD	Ph:  970-212-7600
	Poudre Valley Hospital
		Clinical Trials Office - Poudre Valley Hospital	Ph:  970-495-8226
	Grand Junction
	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	Greeley
	North Colorado Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	Lone Tree
	Sky Ridge Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	Longmont
	Hope Cancer Care Center at Longmont United Hospital
		Eduardo Pajon, MD	Ph:  303-777-2663
	Loveland
	McKee Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	Pueblo
	St. Mary - Corwin Regional Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	Thornton
	North Suburban Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	Wheat Ridge