Letrozole After Tamoxifen in Treating Women With Breast Cancer

Phase 3

Completed

• Conditions: Breast Cancer
• Interventions: Drug: letrozole; Other: placebo

• Registration Number: NCT00003140
• Lead Sponsor: NCIC Clinical Trials Group

Brief Summary

RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by reducing the production of estrogen.

PURPOSE: This randomized phase III trial is studying letrozole to see how well it works in treating women with breast cancer who have received tamoxifen for at least 5 years.

Detailed Description

OBJECTIVES:

Primary

* Compare the disease-free survival and overall survival of postmenopausal women with primary breast cancer who have completed at least five years of adjuvant aromatase inhibitor as initial therapy or after tamoxifen treated with letrozole or placebo.

Secondary

* Compare the incidence of contralateral breast cancer in patients treated with these regimens.

* Evaluate the long-term clinical and laboratory safety of letrozole, in terms of lipid profile, cardiovascular morbidity and mortality, incidence of bone fractures, change in bone density, and common toxic effects, in this patient population.

* Compare the quality of life of patients treated with these regimens. Re-randomization

Primary

* Compare disease-free survival of patients who, after receiving at least 4.5 years of letrozole, are re-randomized to receive an additional 5 years of letrozole vs placebo.

Secondary

* Determine whether common genetic polymorphisms for genes encoding proteins involved in pharmacokinetic and/or pharmacodynamic pathways for letrozole contribute to individual variation in toxicity and efficacy of letrozole therapy.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to receptor status (positive vs unknown), lymph node status (negative vs positive vs unknown), prior adjuvant chemotherapy (yes vs no), interval between last dose of aromatase inhibitor therapy and randomization (\< 6 months vs 6 months-2 years), and duration of prior tamoxifen use (0 years vs \< 2 years vs 2-4.5 years vs \> 4.5 years). 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 5 years in the absence of disease progression or unacceptable toxicity. Patients in arm II may then be offered oral letrozole once daily for up to 5 years.

Quality of life is assessed at baseline, at 6 months, and then annually for 4.5 years.

* Double-blind, re-randomization:

Patients who complete ≥ 4.5 years of letrozole (arm I) and who did not experience recurrent disease or new primary breast cancer, including ductal carcinoma in situ, may participate in the double-blind, placebo-controlled, re-randomization portion of the study. Patients are stratified according to lymph node status at enrollment (negative vs positive vs unknown), prior adjuvant chemotherapy (yes vs no), and interval between last dose of letrozole and re-randomization (\<6 months vs 6 months to 2 years). Common genetic single nucleotide polymorphisms for genes encoding proteins involved in pharmacokinetic and/or pharmacodynamic pathways for letrozole are analyzed in order to determine if these single nucleotide polymorphisms contribute to individual variation in toxicity and efficacy of letrozole therapy.

Quality of life is assessed as during the first randomization.

Patients are followed annually.

PROJECTED ACCRUAL: A total of 4,700 patients will be accrued for this study.

Study Timeline

• Study Start: 1998-08-24
• Study First Submitted: 1999-11-01
• Study First Submitted QC: 2003-01-26
• Study First Posted: 2003-01-27
• Primary Completion: 2003-08-22
• Study Completion: 2003-10
• Status Verified: 2012-03
• Last Update Submitted: 2020-09-15
• Last Update Posted: 2020-09-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 5187

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I	letrozole	Patients receive oral letrozole once daily.
Arm II	placebo	Patients receive oral placebo once daily.

Primary Outcome Measures

Name	Time	Method
Disease-free survival	5 years

Trial Locations

Locations (57)

Lethbridge Cancer Centre; 🇨🇦 Lethbridge, Alberta, Canada

BCCA - Cancer Centre for the Southern Interior; 🇨🇦 Kelowna, British Columbia, Canada

NRGH - Nanaimo Cancer Clinic; 🇨🇦 Nanaimo, British Columbia, Canada

Penticton Regional Hospital; 🇨🇦 Penticton, British Columbia, Canada

BCCA - Fraser Valley Cancer Centre; 🇨🇦 Surrey, British Columbia, Canada

BCCA - Vancouver Cancer Centre; 🇨🇦 Vancouver, British Columbia, Canada

BCCA - Vancouver Island Cancer Centre; 🇨🇦 Victoria, British Columbia, Canada

CancerCare Manitoba; 🇨🇦 Winnipeg, Manitoba, Canada

The Moncton Hospital; 🇨🇦 Moncton, New Brunswick, Canada

The Vitalite Health Network - Dr. Leon Richard; 🇨🇦 Moncton, New Brunswick, Canada

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