Overview

This trial is active, not recruiting.

Condition breast cancer
Treatments anastrozole, exemestane, letrozole, tamoxifen citrate
Phase phase 3
Sponsor Gruppo Italiano Mammella (GIM)
Start date March 2007
End date March 2016
Trial size 3600 participants
Trial identifier NCT00541086, CDR0000570041, EU-20764, EUDRACT-2006-004018-42, GIM-3-FATA

Summary

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking use of estrogen by the tumor cells. Anastrozole, letrozole, and exemestane may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known whether giving tamoxifen followed by anastrozole, letrozole, or exemestane is more effective than giving anastrozole, letrozole, or exemestane alone in treating breast cancer.

PURPOSE: This randomized phase III trial is studying giving tamoxifen followed by either anastrozole, letrozole, or exemestane to see how well it works compared to anastrozole, letrozole, or exemestane alone in treating postmenopausal women with hormone-responsive invasive breast cancer that has been completely removed by surgery.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model factorial assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Up-front adjuvant anastrozole for 5 years
anastrozole
1 mg per day, orally
(Experimental)
Up-front adjuvant exemestane for 5 years
exemestane
25 mg per day, orally
(Experimental)
Up-front adjuvant letrozole for 5 years
letrozole
2.5 mg per day, orally
(Active Comparator)
Switch adjuvant treatment with tamoxifen for 2 years followed by anastrozole for 3 years
anastrozole
1 mg per day, orally
tamoxifen citrate
20 mg per day, orally
(Active Comparator)
Switch adjuvant treatment with tamoxifen for 2 years followed by exemestane for 3 years
exemestane
25 mg per day, orally
tamoxifen citrate
20 mg per day, orally
(Active Comparator)
Switch adjuvant treatment with tamoxifen for 2 years followed by letrozolefor 3 years
letrozole
2.5 mg per day, orally
tamoxifen citrate
20 mg per day, orally

Primary Outcomes

Measure
Disease-free survival
time frame: 5 years

Secondary Outcomes

Measure
Overall Survival
time frame: 5 years
Distant metastasis-free survival
time frame: 5 years
Cumulative incidence of contralateral breast cancer as first event
time frame: 5 years
Breast cancer-free survival
time frame: 5 years
Cumulative incidence and type of second non-breast invasive cancer
time frame: 5 years
Effects on lipid profile
time frame: 5 years
Toxicity as assessed by NCI CTCAE v3.0
time frame: 5 years

Eligibility Criteria

Female participants at least 18 years old.

DISEASE CHARACTERISTICS: - Histologically confirmed invasive breast cancer completely removed by surgery - Any T, any N - No recurrent or metastatic disease - Estrogen or progesterone receptor-positive disease in primary tumor, as defined by 1 of the following: - At least 10% of tumor cells positive by immunohistochemistry - At least 10 fmol/mg cytosol protein by ligand binding assay - Patients with HER-2/neu positive tumors are eligible provided they receive trastuzumab (Herceptin®) according to the registered schedule PATIENT CHARACTERISTICS: - Female - Postmenopausal, defined by ≥ 1 of the following: - Age ≥ 60 years - Age 45-59 and satisfying 1 or more of the following criteria: - Amenorrhea for ≥ 12 months AND intact uterus - Amenorrhea (secondary to hysterectomy, hormone replacement therapy (HRT), or chemotherapy) for < 12 months AND follicle-stimulating hormone within the postmenopausal range - Underwent prior bilateral oophorectomy at any age >18 years - No concurrent illness that contraindicates adjuvant endocrine treatment - No other invasive breast cancer or invasive malignancy within the past 10 years, except adequately cone-biopsied squamous cell or basal cell skin cancer or carcinoma in situ of the cervix - No concurrent disease that would place the patient at unusual risk PRIOR CONCURRENT THERAPY: - See Disease Characteristics - Adjuvant or neoadjuvant chemotherapy must be completed prior to study entry - At least 1 month since prior and no concurrent HRT - More than 30 days since prior systemic investigational drugs - No prior tamoxifen as part of any breast cancer prevention study - Prior or concurrent locoregional radiotherapy allowed - No other concurrent experimental drugs - No concurrent bisphosphonates, unless indicated as treatment for osteoporosis

Additional Information

Official title A Phase III Study Comparing Anastrozole, Letrozole and Exemestane, Upfront (for 5 Years) or Sequentially (for 3 Years After 2 Years of Tamoxifen), as Adjuvant Treatment of Postmenopausal Patients With Endocrine-responsive Breast Cancer
Description OBJECTIVES: - To compare sequential tamoxifen for 2 years followed by anastrozole, letrozole, or exemestane for 3 years vs anastrozole, letrozole, or exemestane for 5 years in terms of disease-free survival in postmenopausal women with nonrecurrent, nonmetastatic invasive endocrine-responsive breast cancer. - To compare disease-free survival in patients treated with anastrozole vs letrozole vs exemestane. OUTLINE: This is a multicenter study. Patients are stratified according to hormone receptor status (estrogen receptor [ER]-positive and progesterone [PgR] receptor-positive disease vs ER-positive and PgR-negative disease vs ER-negative and PgR-positive disease vs ER- or PgR-positive disease or ER or PgR status unknown), HER-2/neu status (positive [3+ by IHC or positive by fluorescence in situ hybridization ( FISH)] vs negative vs unknown), prior chemotherapy (none vs adjuvant vs neoadjuvant vs both adjuvant and neoadjuvant), and nodal status (pN0 vs pN1 vs pN2 vs pN3). Patients are randomized to 1 of 6 treatment arms. - Arm I: Patients receive oral anastrozole once daily for 5 years. - Arm II: Patients receive oral exemestane once daily for 5 years. - Arm III: Patients receive oral letrozole once daily for 5 years. - Arm IV: Patients receive oral tamoxifen citrate once daily for 2 years followed by oral anastrazole once daily for 3 years. - Arm V: Patients receive oral tamoxifen citrate once daily for 2 years followed by oral exemestane once daily for 3 years. - Arm VI: Patients receive oral tamoxifen citrate once daily for 2 years followed by oral letrozole once daily for 3 years. Treatment in all arms continues in the absence of disease recurrence or unacceptable toxicity. After completion of study therapy, patients are followed periodically.
Trial information was received from ClinicalTrials.gov and was last updated in January 2015.
Information provided to ClinicalTrials.gov by Gruppo Italiano Mammella (GIM).