A Double Blind Randomization to Letrozole or Placebo for Women Previously Diagnosed With Primary Breast Cancer Completing Five Years of Adjuvant Aromatase Inhibitor Either as Initial Therapy or After Tamoxifen (Including Those in The MA.17 Study)
Overview
- Phase
- Phase 3
- Intervention
- letrozole
- Conditions
- Breast Cancer
- Sponsor
- Canadian Cancer Trials Group
- Enrollment
- 1918
- Locations
- 43
- Primary Endpoint
- Disease-free Survival (DFS)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief 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 in women with breast cancer who have already received 5 years of aromatase inhibitor therapy.
PURPOSE: This randomized phase III trial is studying letrozole to see how well it works compared with a placebo in treating women with primary breast cancer who have received 5 years of aromatase inhibitor therapy.
Detailed Description
OBJECTIVES: Primary * To compare the disease-free survival of women with primary breast cancer treated with letrozole vs placebo after completing approximately 5 years (i.e., 4½ - 6 years) of aromatase inhibitor therapy (e.g., letrozole, anastrozole, or exemestane). Secondary * To compare the effect of these drugs on overall (all cause specific) mortality of these patients. * To compare the incidence of contralateral breast cancer in patients treated with these drugs. * To evaluate the long-term clinical and laboratory safety of aromatase inhibitor therapy, particularly cardiovascular morbidity and mortality (e.g., significant coronary artery disease, including myocardial infarction and angina requiring percutaneous transluminal coronary angioplasty or coronary artery bypass graft, fatal and nonfatal strokes, and all vascular deaths); incidence of all bone fractures (with particular emphasis on hip and wrist fractures as indicators of osteoporosis); changes in bone density; and common toxicities. * To compare overall quality of life (QOL) and menopausal-specific QOL of patients treated with these drugs. OUTLINE: This is a multicenter study. Patients are stratified according to lymph node status at diagnosis (negative vs positive vs unknown), prior adjuvant chemotherapy (yes vs no), interval between last dose of aromatase inhibitor therapy and study randomization (\< 6 months vs 6 months to 2 years), and duration of prior tamoxifen citrate use (0 vs \< 2 years vs 2 - 4½ years vs \> 4½ years). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. * Arm II: Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. Patients undergo bone mineral density measurement by DEXA scan at baseline (if not done within 12 months of study entry), at 24 and 48 months during study therapy, and at the completion of study therapy. Some patients also complete quality-of-life questionnaires at baseline and at 12, 24, 36, 48, and 60 months. After completion of study therapy, patients are followed annually.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Letrozole
Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy.
Intervention: letrozole
Placebo
Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy.
Intervention: placebo
Outcomes
Primary Outcomes
Disease-free Survival (DFS)
Time Frame: Unitil the end of study with a median follow up of 75 months
It is defined as the months from the day of randomization to the earliest date when a recurrence of the primary disease (recurrence in the breast, chest wall and nodal sites or the development of metastatic disease) or a contralateral breast cancer was observed. Subjects who died without recurrence of the primary disease or the development of the contralateral breast cancer were censored at their death date. If a patient has not recurred, developed a contralateral breast cancer, or died, disease-free survival was censored on the date of the last day the patient was known to be alive. Probability of disease free survival at 5 years is estimated and reported.
Secondary Outcomes
- Overall Survival (OS)(Until the end of study with a median follow-up of 75 months)
- Incidence of Contralateral Breast Cancer(10 years)
- Change From Baseline in Role Function- Physical Scale on SF(Short Form)-36 Health Survey(8 years)