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 - Full Text View

Sponsor:	Gruppo Italiano Mammella (GIM)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00541086

Purpose

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.

Condition	Intervention	Phase
Breast Cancer	Drug: anastrozole Drug: exemestane Drug: letrozole Drug: tamoxifen citrate Procedure: adjuvant therapy	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Tamoxifen Tamoxifen citrate Exemestane Letrozole Anastrozole

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Disease-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall Survival [ Designated as safety issue: No ]
Distant metastasis-free survival [ Designated as safety issue: No ]
Cumulative incidence of contralateral breast cancer as first event [ Designated as safety issue: No ]
Breast cancer-free survival [ Designated as safety issue: No ]
Cumulative incidence and type of second non-breast invasive cancer [ Designated as safety issue: No ]
Effects on lipid profile [ Designated as safety issue: No ]
Toxicity as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]

Estimated Enrollment:	10000
Study Start Date:	March 2007
Estimated Primary Completion Date:	March 2016 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00541086

Locations

Italy
Federico II University Medical School	Recruiting
Naples, Italy, 80131
Contact: Sabino De Placido, MD 39-081-746-3660 deplacid@unina.it
Istituto Nazionale per lo Studio e la Cura dei Tumori	Recruiting
Naples, Italy, 80131
Contact: Francesco Perrone, MD 39-81-590-3571
Seconda Universita di Napoli	Recruiting
Naples, Italy, 80138
Contact: Ciro Gallo 39-81-566-6021
Arcispedale S. Maria Nuova	Recruiting
Reggio Emilia, Italy, 42100
Contact: Corrado Boni, MD 39-522-296-546 boni.corrado@asmn.re.it
Istituti Fisioterapici Ospitalieri - Roma	Recruiting
Rome, Italy, 00128
Contact: Francesco Cognetti, MD 39-06-5266-6919 cognetti@ifo.it

Sponsors and Collaborators

Gruppo Italiano Mammella (GIM)

Investigators

Study Chair:

Sabino De Placido, MD

Federico II University

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

ClinicalTrials.gov Identifier:	NCT00541086 History of Changes
Other Study ID Numbers:	CDR0000570041, GIM-3-FATA, EUDRACT-2006-004018-42, EU-20764
Study First Received:	October 5, 2007
Last Updated:	November 10, 2010
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Adjuvants, Immunologic
Tamoxifen
Anastrozole
Exemestane
Letrozole
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Bone Density Conservation Agents
Estrogen Antagonists
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012