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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ClinicalTrials.gov Identifier: NCT00541086 |
Recruitment Status : Unknown
Verified February 2020 by Gruppo Italiano Mammella (GIM).
Recruitment status was: Active, not recruiting
First Posted : October 8, 2007
Last Update Posted : February 7, 2020
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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 or disease | Intervention/treatment | Phase |
---|---|---|
Breast Cancer | Drug: anastrozole Drug: exemestane Drug: letrozole Drug: tamoxifen citrate | Phase 3 |
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.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 3697 participants |
Allocation: | Randomized |
Intervention Model: | Factorial Assignment |
Masking: | None (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 |
Actual Study Start Date : | March 2007 |
Estimated Primary Completion Date : | July 2020 |
Estimated Study Completion Date : | July 2020 |
Arm | Intervention/treatment |
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Experimental: A - anastrozole
Up-front adjuvant anastrozole for 5 years
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Drug: anastrozole
1 mg per day, orally |
Experimental: B - exemestane
Up-front adjuvant exemestane for 5 years
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Drug: exemestane
25 mg per day, orally |
Experimental: C - letrozole
Up-front adjuvant letrozole for 5 years
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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
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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 |
- Disease-free survival [ Time Frame: 5 years ]
- Overall Survival [ Time Frame: 5 years ]
- Distant metastasis-free survival [ Time Frame: 5 years ]
- Cumulative incidence of contralateral breast cancer as first event [ Time Frame: 5 years ]
- Breast cancer-free survival [ Time Frame: 5 years ]
- Cumulative incidence and type of second non-breast invasive cancer [ Time Frame: 5 years ]
- Effects on lipid profile [ Time Frame: 5 years ]
- Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: 5 years ]
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, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
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Histologically confirmed invasive breast cancer completely removed by surgery
- Any T, any N
- No recurrent or metastatic disease
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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
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Postmenopausal, defined by ≥ 1 of the following:
- Age ≥ 60 years
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00541086
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 |
Study Chair: | Sabino De Placido, MD | Federico II University |
Responsible Party: | Gruppo Italiano Mammella (GIM) |
ClinicalTrials.gov Identifier: | NCT00541086 |
Other Study ID Numbers: |
CDR0000570041 GIM-3-FATA EUDRACT-2006-004018-42 EU-20764 |
First Posted: | October 8, 2007 Key Record Dates |
Last Update Posted: | February 7, 2020 |
Last Verified: | February 2020 |
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 |
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Tamoxifen Letrozole Anastrozole Exemestane Molecular Mechanisms of Pharmacological Action Antineoplastic Agents |
Aromatase Inhibitors Steroid Synthesis Inhibitors Enzyme Inhibitors Estrogen Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antineoplastic Agents, Hormonal Selective Estrogen Receptor Modulators Estrogen Receptor Modulators Bone Density Conservation Agents |