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

NCT00541086 | Unknown Phase 3 DMC

• 4 other identifiers: CDR0000570041GIM-3-FATAEUDRACT-2006-004018-42EU-20764
• Study Type: interventional
• Target: 3,697
• Locations: 1 country
• Sites: 5

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.

Conditions

Breast Cancer

Keywords

stage IA breast cancer; stage IB breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; estrogen receptor-positive breast cancer; progesterone receptor-positive breast cancer

Outcome Measures

Primary Outcomes (1)

• Disease-free survival

  5 years

Secondary Outcomes (7)

• Overall Survival

  5 years

• Distant metastasis-free survival

  5 years

• Cumulative incidence of contralateral breast cancer as first event

  5 years

• Breast cancer-free survival

  5 years

• Cumulative incidence and type of second non-breast invasive cancer

  5 years

Study Arms (6)

A - anastrozole

EXPERIMENTAL

Up-front adjuvant anastrozole for 5 years

Drug: anastrozole

B - exemestane

EXPERIMENTAL

Up-front adjuvant exemestane for 5 years

Drug: exemestane

C - letrozole

EXPERIMENTAL

Up-front adjuvant letrozole for 5 years

Drug: letrozole

D - tamoxifen followed by anastrozole

ACTIVE COMPARATOR

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

Drug: anastrozole; Drug: tamoxifen citrate

E - tamoxifen followed by exemestane

ACTIVE COMPARATOR

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

Drug: exemestane; Drug: tamoxifen citrate

F - tamoxifen followed by letrozole

ACTIVE COMPARATOR

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

Drug: letrozole; Drug: tamoxifen citrate

Interventions

anastrozole DRUG

1 mg per day, orally

A - anastrozole; D - tamoxifen followed by anastrozole

exemestane DRUG

25 mg per day, orally

B - exemestane; E - tamoxifen followed by exemestane

letrozole DRUG

2.5 mg per day, orally

C - letrozole; F - tamoxifen followed by letrozole

tamoxifen citrate DRUG

20 mg per day, orally

D - tamoxifen followed by anastrozole; E - tamoxifen followed by exemestane; F - tamoxifen followed by letrozole

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Gruppo Italiano Mammella (GIM): lead

Study Sites (5)

Federico II University Medical School

Naples, 80131, Italy

Location

Istituto Nazionale per lo Studio e la Cura dei Tumori

Naples, 80131, Italy

Location

Seconda Universita di Napoli

Naples, 80138, Italy

Location

Arcispedale S. Maria Nuova

Reggio Emilia, 42100, Italy

Location

Istituti Fisioterapici Ospitalieri - Roma

Rome, 00128, Italy

Location

Related Publications (1)

• 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.

  PMID: 29482983 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Anastrozole; exemestane; Letrozole; Tamoxifen

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Sabino De Placido, MD

  Federico II University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2007
• First Posted: October 8, 2007
• Study Start: March 1, 2007
• Primary Completion: July 1, 2020
• Study Completion: July 1, 2020
• Last Updated: February 7, 2020

Record last verified: 2020-02

Locations

IT (5)