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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

Primary Purpose

Breast Cancer

Status
Unknown status
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
anastrozole
exemestane
letrozole
tamoxifen citrate
Sponsored by
Gruppo Italiano Mammella (GIM)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Federico II University Medical School
  • Istituto Nazionale per lo Studio e la Cura dei Tumori
  • Seconda Universita di Napoli
  • Arcispedale S. Maria Nuova
  • Istituti Fisioterapici Ospitalieri - Roma

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Active Comparator

Active Comparator

Active Comparator

Arm Label

A - anastrozole

B - exemestane

C - letrozole

D - tamoxifen followed by anastrozole

E - tamoxifen followed by exemestane

F - tamoxifen followed by letrozole

Arm Description

Up-front adjuvant anastrozole for 5 years

Up-front adjuvant exemestane for 5 years

Up-front adjuvant letrozole for 5 years

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

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

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

Outcomes

Primary Outcome Measures

Disease-free survival

Secondary Outcome Measures

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

Full Information

First Posted
October 5, 2007
Last Updated
February 5, 2020
Sponsor
Gruppo Italiano Mammella (GIM)
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1. Study Identification

Unique Protocol Identification Number
NCT00541086
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Unknown status
Study Start Date
March 2007 (Actual)
Primary Completion Date
July 2020 (Anticipated)
Study Completion Date
July 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gruppo Italiano Mammella (GIM)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
3697 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A - anastrozole
Arm Type
Experimental
Arm Description
Up-front adjuvant anastrozole for 5 years
Arm Title
B - exemestane
Arm Type
Experimental
Arm Description
Up-front adjuvant exemestane for 5 years
Arm Title
C - letrozole
Arm Type
Experimental
Arm Description
Up-front adjuvant letrozole for 5 years
Arm Title
D - tamoxifen followed by anastrozole
Arm Type
Active Comparator
Arm Description
Switch adjuvant treatment with tamoxifen for 2 years followed by anastrozole for 3 years
Arm Title
E - tamoxifen followed by exemestane
Arm Type
Active Comparator
Arm Description
Switch adjuvant treatment with tamoxifen for 2 years followed by exemestane for 3 years
Arm Title
F - tamoxifen followed by letrozole
Arm Type
Active Comparator
Arm Description
Switch adjuvant treatment with tamoxifen for 2 years followed by letrozolefor 3 years
Intervention Type
Drug
Intervention Name(s)
anastrozole
Intervention Description
1 mg per day, orally
Intervention Type
Drug
Intervention Name(s)
exemestane
Intervention Description
25 mg per day, orally
Intervention Type
Drug
Intervention Name(s)
letrozole
Intervention Description
2.5 mg per day, orally
Intervention Type
Drug
Intervention Name(s)
tamoxifen citrate
Intervention Description
20 mg per day, orally
Primary Outcome Measure Information:
Title
Disease-free survival
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Overall Survival
Time Frame
5 years
Title
Distant metastasis-free survival
Time Frame
5 years
Title
Cumulative incidence of contralateral breast cancer as first event
Time Frame
5 years
Title
Breast cancer-free survival
Time Frame
5 years
Title
Cumulative incidence and type of second non-breast invasive cancer
Time Frame
5 years
Title
Effects on lipid profile
Time Frame
5 years
Title
Toxicity as assessed by NCI CTCAE v3.0
Time Frame
5 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sabino De Placido, MD
Organizational Affiliation
Federico II University
Official's Role
Study Chair
Facility Information:
Facility Name
Federico II University Medical School
City
Naples
ZIP/Postal Code
80131
Country
Italy
Facility Name
Istituto Nazionale per lo Studio e la Cura dei Tumori
City
Naples
ZIP/Postal Code
80131
Country
Italy
Facility Name
Seconda Universita di Napoli
City
Naples
ZIP/Postal Code
80138
Country
Italy
Facility Name
Arcispedale S. Maria Nuova
City
Reggio Emilia
ZIP/Postal Code
42100
Country
Italy
Facility Name
Istituti Fisioterapici Ospitalieri - Roma
City
Rome
ZIP/Postal Code
00128
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
29482983
Citation
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. Erratum In: Lancet Oncol. 2018 Apr;19(4):e184.
Results Reference
derived

Learn more about this trial

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

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