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Summary

for females ages 18–120 (full criteria)
at San Francisco, California and other locations
study started
estimated completion:

Description

Summary

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known whether letrozole is more effective than a placebo in treating patients with hormone receptor-positive breast cancer.

PURPOSE: This randomized phase III trial is studying letrozole to see how well it works compared with a placebo in treating postmenopausal women who have received hormone therapy for hormone receptor-positive breast cancer.

Official Title

A Clinical Trial to Determine the Efficacy of Five Years of Letrozole Compared to 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

Details

OBJECTIVES:

Primary

  • Determine whether or not prolonged adjuvant hormonal therapy comprising letrozole vs placebo will improve disease-free survival 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.
  • Compare the disease-free survival of patients treated with these regimens.

Secondary

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

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.

  • Group I: Patients receive oral placebo once daily.
  • Group II: Patients receive oral letrozole 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.

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

Keywords

Breast Cancer stage I breast cancer stage II breast cancer stage IIIA breast cancer Breast Neoplasms Hormones Letrozole

Eligibility

For females ages 18–120

Eligibility Criteria

  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (0 = fully active, able to carry on all pre-disease performance without restriction; 1 = restricted in physically strenuous activity but ambulatory).
  • Patients must be postmenopausal at the time of randomization. (Note: Premenopausal or perimenopausal women requiring therapy with luteinizing hormone-releasing hormone[LHRH] analogs to suppress ovarian function are not eligible.) For study purposes,postmenopausal is defined as: age 56 or older with no spontaneous menses for at least 12 months prior to study entry, or age 55 or younger with no spontaneous menses for at least 12 months prior to study entry (e.g., spontaneous or secondary to hysterectomy)AND with a documented estradiol level in the postmenopausal range according to local institutional/laboratory standards, or a prior documented bilateral oophorectomy.
  • The patient must have remained disease-free from the time of initial breast cancer diagnosis until the time of randomization.
  • The patient must have had histologically-confirmed invasive carcinoma of the breast by diagnostic core needle biopsy or by final pathologic evaluation of the surgical specimen.
  • Patients who received neoadjuvant chemotherapy must have been clinical Stage I, II, or IIIA. For patients who received adjuvant chemotherapy, the primary tumor must have been T1-3 on pathologic evaluation and ipsilateral nodes must have been pN0, pN1(pN1mi, pN1a, pN1b, pN1c), pN2a, pN3a, or pN3b.
  • The primary tumor must have been estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive. (Patients who had a tumor that was considered to be borderline for hormone receptor positivity and who were treated with tamoxifen and/or an aromatases inhibitor (AI) are eligible for this study.)
  • Patients must have undergone either a lumpectomy with axillary nodal staging followed by breast radiotherapy or a total mastectomy with axillary nodal staging. (Acceptable axillary nodal staging procedures include sentinel node biopsy alone, if sentinel nodes were negative on hematoxylin and eosin (H&E) staining.)
  • The duration of the patient's hormonal therapy following breast cancer diagnosis must have been 57-63 months from the first dose regardless of the number of missed doses.Hormonal therapy must have consisted of an AI or a combination of up to 3 years of tamoxifen followed by an AI. Tamoxifen may not have been given during years 4 and 5 of the 5 years of adjuvant hormonal therapy. (Note: Patients must discontinue their adjuvant AI therapy at the time of randomization.)
  • Optional Letrozole Registration Program for patients who have not yet completed 5 years of hormonal therapy. (Note: As of September 5, 2008, the optional NSABP B-42 Registration Program closed to patient enrollment. Accrual and data collection for the NSABP B-42 randomized treatment trial continues as planned.) In order to have a predominantly letrozole-treated population for B-42 study entry, patients who have had a minimum of 2 years of hormonal therapy and who are currently on tamoxifen (for up to 3 years) or an AI may be offered letrozole at no cost until they complete 5 total years of initial adjuvant hormonal therapy.
  • B-42 randomization must be within 6 months following completion of 5 years (57-63 months) of initial adjuvant hormonal therapy.
  • At the time of randomization, the patient must have had the following: history and physical exam within 3 months demonstrating no findings suggestive of recurrent breast cancer; bilateral mammogram within 1 year (unilateral if patient had a mastectomy);mammogram not required if patient had a prophylactic contralateral mastectomy; bone mineral density (BMD) testing within 1 year; and fasting lipid profile (total cholesterol, LDL-C, HDL-C, and triglycerides) with a total cholesterol value less than or equal to grade 1 (according to CTCAE v3.0), with or without cholesterol-lowering therapy.
  • within 1 year if the patient has a history of hypercholesterolemia controlled with cholesterol-lowering therapy and/or therapeutic lifestyle changes or if the patient has a history of one or more of the following risk factors for future cardiovascular events: diabetes, hypertension, obesity, tobacco use,hypertriglyceridemia, documented coronary artery disease, or family history of premature coronary heart disease.
  • within 2 years for all other patients.

Ineligibility Criteria

  • Patients with one or more of the following conditions will be ineligible for this study:
  • History of non-traumatic osteoporotic fracture of wrist, hip, or spine.
  • Diagnosis of bilateral breast cancer including ductal carcinoma in situ(DCIS)[(synchronous or metachronous].
  • Other malignancies unless the patient is considered to be disease-free for 5 or more years prior to randomization, and is deemed by their physician to be at low risk for recurrence. Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: carcinoma in situ of the cervix, colon carcinoma in situ,melanoma in situ, and basal cell and squamous cell carcinoma of the skin.
  • Sex hormonal therapy, e.g., estrogen- or progesterone-replacement therapy or oral contraceptives. These patients are eligible only if this therapy is discontinued prior to randomization.
  • Therapy with any hormonal agent such as raloxifene for management of osteoporosis.Patients are eligible only if these medications are discontinued prior to study entry.
  • Administration of any investigational agent within 30 days before study entry.

Locations

  • San Francisco General Hospital Medical Center
    San Francisco, California, 94110, United States
  • Kaiser Permanente Medical Center - San Francisco Geary Campus
    San Francisco, California, 94115, United States
  • California Pacific Medical Center - California Campus
    San Francisco, California, 94118, United States
  • Cancer Care Associates
    Fresno, California, 93720, United States
  • Kaiser Permanente Medical Center - South San Francisco
    South San Francisco, California, 94080, United States
  • Alta Bates Summit Medical Center - Summit Campus
    Oakland, California, 94609, United States
  • Bay Area Breast Surgeons, Incorporated
    Oakland, California, 94609, United States
  • CCOP - Bay Area Tumor Institute
    Oakland, California, 94609, United States
  • Larry G Strieff MD Medical Corporation
    Oakland, California, 94609, United States
  • Tom K Lee, Incorporated
    Oakland, California, 94609, United States
  • Alta Bates Summit Comprehensive Cancer Center
    Berkeley, California, 94704, United States
  • Marin Cancer Institute at Marin General Hospital
    Greenbrae, California, 94904, United States
  • Sutter Health - Western Division Cancer Research Group
    Greenbrae, California, 94904, United States
  • Highland General Hospital
    Oakland, California, 94602, United States
  • Kaiser Permanente Medical Center - Richmond
    Richmond, California, 94801, United States
  • Peninsula Medical Center
    Burlingame, California, 94010, United States
  • Kaiser Permanente Medical Center - Oakland
    Oakland, California, 94611, United States
  • Doctors Medical Center - San Pablo Campus
    San Pablo, California, 94806, United States
  • Kaiser Foundation Hospital - San Rafael
    San Rafael, California, 94903, United States
  • East Bay Radiation Oncology Center
    Castro Valley, California, 94546, United States
  • Eden Medical Center
    Castro Valley, California, 94546, United States
  • Valley Medical Oncology Consultants - Castro Valley
    Castro Valley, California, 94546, United States
  • Kaiser Permanente Medical Center - Hayward
    Hayward, California, 94545, United States
  • Contra Costa Regional Medical Center
    Martinez, California, 94553-3156, United States
  • Kaiser Permanente Medical Center - Redwood City
    Redwood City, California, 94063, United States
  • Kaiser Permanente Medical Center - Walnut Creek
    Walnut Creek, California, 94596, United States
  • John Muir/Mt. Diablo Comprehensive Cancer Center
    Walnut Creek, California, 94598, United States
  • Cancer Care Center at John Muir Health - Concord Campus
    Concord, California, 94524-4110, United States
  • Stanford Cancer Center
    Stanford, California, 94305-5824, United States
  • Kaiser Permanente Medical Center - Vallejo
    Vallejo, California, 94589, United States
  • Sutter Solano Medical Center
    Vallejo, California, 94589, United States
  • Kaiser Permanente - Fremont
    Fremont, California, 94538, United States
  • Valley Medical Oncology
    Fremont, California, 94538, United States
  • Valley Care Medical Center
    Pleasanton, California, 94588, United States
  • Valley Medical Oncology Consultants - Pleasanton
    Pleasanton, California, 94588, United States
  • El Camino Hospital Cancer Center
    Mountain View, California, 94040, United States
  • Kaiser Permanente Medical Center - Santa Clara Kiely Campus
    Santa Clara, California, 95051, United States
  • North Bay Cancer Center
    Fairfield, California, 94533, United States
  • Kaiser Permanente Medical Center - Santa Teresa
    San Jose, California, 95119, United States
  • Kaiser Permanente Medical Center - Santa Rosa
    Santa Rosa, California, 95403, United States
  • Kaiser Permanente Medical Facility - Stockton
    Stockton, California, 95210, United States
  • South Sacramento Kaiser-Permanente Medical Center
    Sacramento, California, 95823, United States
  • Sutter Cancer Center
    Sacramento, California, 95816, United States
  • Kaiser Permanente Medical Center - Sacramento
    Sacramento, California, 95825, United States
  • Salinas Valley Memorial Hospital
    Salinas, California, 93901, United States
  • Kaiser Permanente Medical Center - Roseville
    Roseville, California, 95661, United States
  • Sutter Cancer Center at Roseville Medical Center
    Roseville, California, 95661, United States
  • North Valley Breast Clinic
    Redding, California, 96001, United States
  • Providence Saint Joseph Medical Center - Burbank
    Burbank, California, 91505, United States
  • Glendale Memorial Hospital Comprehensive Cancer Center
    Glendale, California, 91204, United States
  • City of Hope Comprehensive Cancer Center
    Duarte, California, 91010-3000, United States
  • Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center
    Pomona, California, 91767, United States
  • USC/Norris Comprehensive Cancer Center and Hospital
    Los Angeles, California, 90089-9181, United States
  • Jonsson Comprehensive Cancer Center at UCLA
    Los Angeles, California, 90095-1781, United States
  • Breastlink Medical Group, Incorporated at Long Beach Memorial Medical Center
    Long Beach, California, 90806, United States
  • Virginia K. Crosson Cancer Center at St. Jude Medical Center
    Fullerton, California, 92835, United States
  • Pacific Shores Medical Group - Long Beach
    Long Beach, California, 90813, United States
  • Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
    Orange, California, 92868, United States
  • St. Joseph Hospital Regional Cancer Center - Orange
    Orange, California, 92868, United States
  • Loma Linda University Cancer Institute at Loma Linda University Medical Center
    Loma Linda, California, 92354, United States
  • University Medical Center of Southern Nevada
    Las Vegas, Nevada, 89102, United States
  • CCOP - Nevada Cancer Research Foundation
    Las Vegas, Nevada, 89106, United States
  • Desert Regional Medical Center Comprehensive Cancer Center
    Palm Springs, California, 92262, United States
  • Lucy Curci Cancer Center at Eisenhower Memorial Hospital and Medical Center
    Rancho Mirage, California, 92270, United States

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
NSABP Foundation Inc
ID
NCT00382070
Phase
Phase 3
Study Type
Interventional
Last Updated
May 4, 2017