Study of Anastrozole, Letrozole, or Exemestane With or Without Tamoxifen in Treating Postmenopausal Women With Hormone-Responsive Breast Cancer That Has Been Completely Removed By Surgery

NCT ID: NCT00541086

Last Updated: 2020-02-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 3697 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31
• Study Completion Date: 2020-07-31

Brief 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.

Detailed 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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A - anastrozole

Up-front adjuvant anastrozole for 5 years

Group Type: EXPERIMENTAL

anastrozole

Intervention Type: DRUG

1 mg per day, orally

B - exemestane

Up-front adjuvant exemestane for 5 years

Group Type: EXPERIMENTAL

exemestane

Intervention Type: DRUG

25 mg per day, orally

C - letrozole

Up-front adjuvant letrozole for 5 years

Group Type: EXPERIMENTAL

letrozole

Intervention Type: DRUG

2.5 mg per day, orally

D - tamoxifen followed by anastrozole

Switch adjuvant treatment with tamoxifen for 2 years followed by anastrozole for 3 years

Group Type: ACTIVE_COMPARATOR

anastrozole

Intervention Type: DRUG

1 mg per day, orally

tamoxifen citrate

Intervention Type: DRUG

20 mg per day, orally

E - tamoxifen followed by exemestane

Switch adjuvant treatment with tamoxifen for 2 years followed by exemestane for 3 years

Group Type: ACTIVE_COMPARATOR

exemestane

Intervention Type: DRUG

25 mg per day, orally

tamoxifen citrate

Intervention Type: DRUG

20 mg per day, orally

F - tamoxifen followed by letrozole

Switch adjuvant treatment with tamoxifen for 2 years followed by letrozolefor 3 years

Group Type: ACTIVE_COMPARATOR

letrozole

Intervention Type: DRUG

2.5 mg per day, orally

tamoxifen citrate

Intervention Type: DRUG

20 mg per day, orally

Interventions

anastrozole

1 mg per day, orally

Intervention Type: DRUG

exemestane

25 mg per day, orally

Intervention Type: DRUG

letrozole

2.5 mg per day, orally

Intervention Type: DRUG

tamoxifen citrate

20 mg per day, orally

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Gruppo Italiano Mammella (GIM)

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sabino De Placido, MD

Role: STUDY_CHAIR

Federico II University

Locations

Federico II University Medical School

Naples, , Italy

Istituto Nazionale per lo Studio e la Cura dei Tumori

Naples, , Italy

Seconda Universita di Napoli

Naples, , Italy

Arcispedale S. Maria Nuova

Reggio Emilia, , Italy

Istituti Fisioterapici Ospitalieri - Roma

Rome, , Italy

Countries

Italy

References

De Placido S, Gallo C, De Laurentiis M, Bisagni G, Arpino G, Sarobba MG, Riccardi F, Russo A, Del Mastro L, Cogoni AA, Cognetti F, Gori S, Foglietta J, Frassoldati A, Amoroso D, Laudadio L, Moscetti L, Montemurro F, Verusio C, Bernardo A, Lorusso V, Gravina A, Moretti G, Lauria R, Lai A, Mocerino C, Rizzo S, Nuzzo F, Carlini P, Perrone F; GIM Investigators. Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial. Lancet Oncol. 2018 Apr;19(4):474-485. doi: 10.1016/S1470-2045(18)30116-5. Epub 2018 Feb 23.

Reference Type: DERIVED

PMID: 29482983 (View on PubMed)

Other Identifiers

GIM-3-FATA

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2006-004018-42

Identifier Type: -

Identifier Source: secondary_id

EU-20764

Identifier Type: -

Identifier Source: secondary_id

CDR0000570041

Identifier Type: -

Identifier Source: org_study_id