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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gruppo Italiano Mammella (GIM)
ClinicalTrials.gov Identifier:
NCT00541086
First received: October 5, 2007
Last updated: January 20, 2015
Last verified: January 2015
  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
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
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:


Further study details as provided by Gruppo Italiano Mammella (GIM):

Primary Outcome Measures:
  • Disease-free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Distant metastasis-free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Cumulative incidence of contralateral breast cancer as first event [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Breast cancer-free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Cumulative incidence and type of second non-breast invasive cancer [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Effects on lipid profile [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 3600
Study Start Date: March 2007
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A - anastrozole
Up-front adjuvant anastrozole for 5 years
Drug: anastrozole
1 mg per day, orally
Experimental: B - exemestane
Up-front adjuvant exemestane for 5 years
Drug: exemestane
25 mg per day, orally
Experimental: C - letrozole
Up-front adjuvant letrozole for 5 years
Drug: letrozole
2.5 mg per day, orally
Active Comparator: D - tamoxifen followed by anastrozole
Switch adjuvant treatment with tamoxifen for 2 years followed by anastrozole for 3 years
Drug: anastrozole
1 mg per day, orally
Drug: tamoxifen citrate
20 mg per day, orally
Active Comparator: E - tamoxifen followed by exemestane
Switch adjuvant treatment with tamoxifen for 2 years followed by exemestane for 3 years
Drug: exemestane
25 mg per day, orally
Drug: tamoxifen citrate
20 mg per day, orally
Active Comparator: F - tamoxifen followed by letrozole
Switch adjuvant treatment with tamoxifen for 2 years followed by letrozolefor 3 years
Drug: letrozole
2.5 mg per day, orally
Drug: tamoxifen citrate
20 mg per day, orally

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
Italy
Federico II University Medical School
Naples, Italy, 80131
Istituto Nazionale per lo Studio e la Cura dei Tumori
Naples, Italy, 80131
Seconda Universita di Napoli
Naples, Italy, 80138
Arcispedale S. Maria Nuova
Reggio Emilia, Italy, 42100
Istituti Fisioterapici Ospitalieri - Roma
Rome, Italy, 00128
Sponsors and Collaborators
Gruppo Italiano Mammella (GIM)
Investigators
Study Chair: Sabino De Placido, MD Federico II University
  More Information

Additional Information:
No publications provided

Responsible Party: Gruppo Italiano Mammella (GIM)
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: January 20, 2015
Health Authority: Italy: Ethics Committee

Keywords provided by Gruppo Italiano Mammella (GIM):
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
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Anastrozole
Exemestane
Letrozole
Tamoxifen
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Aromatase Inhibitors
Bone Density Conservation Agents
Enzyme Inhibitors
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Selective Estrogen Receptor Modulators
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015