Letrozole After Tamoxifen in Treating Women With Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): letrozole; placebo
Intervention type(s): Drug; Other
Intervention description(s): Given orally; Given orally
Other intervention name(s): Femara
Intervention MeSH terms: Letrozole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: stage I breast cancer; stage II breast cancer; stage IIIA breast cancer