August 6, 2003
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August 7, 2003
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July 14, 2015
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April 5, 2016
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January 2, 2024
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November 3, 2003
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March 11, 2011 (Final data collection date for primary outcome measure)
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Disease-free Survival [ Time Frame: 5-year estimate reported at a median follow-up of 72 months ] Estimated percentage of patients alive and disease-free at 5 years from randomization, where disease-free survival is defined as the time from randomization to the first appearance of one of the following: invasive breast cancer recurrence at local, regional, or distant site, invasive contralateral breast cancer, second (non-breast) invasive cancer, or death without cancer event; or censored at date of last follow up.
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Not Provided
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- Breast Cancer-free Interval [ Time Frame: 5-year estimate reported at a median follow-up of 72 months ]
Estimated percentage of patients alive and disease-free at 5 years from randomization, where breast cancer-free interval is defined as the time from randomization to the invasive breast cancer recurrence at local, regional, or distant site, or invasive contralateral breast cancer; or censored at date of last follow up.
- Distant Recurrence-free Interval [ Time Frame: 5-year estimates reported at a median follow-up of 72 months ]
Estimated percentage of patients alive and disease-free at 5 years from randomization, where distant recurrence-free interval is defined as the time from randomization to breast cancer recurrence at a distant site; or censored at date of last follow-up
- Overall Survival [ Time Frame: 8-year estimates, reported at a median follow-up of 9 years ]
Estimated percentage of patients alive at 8 years from randomization, where overall survival is defined as the time from randomization to death from any cause; or censored at date last known alive.
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Not Provided
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Not Provided
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Not Provided
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Triptorelin With Either Exemestane or Tamoxifen in Treating Premenopausal Women With Hormone-Responsive Breast Cancer
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A Phase III Trial Evaluating The Role Of Exemestane Plus GnRH Analogue As Adjuvant Therapy For Premenopausal Women With Endocrine Responsive Breast Cancer
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RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using triptorelin, exemestane, and tamoxifen may fight breast cancer by blocking the use of estrogen. It is not yet known whether giving triptorelin together with exemestane is more effective than triptorelin and tamoxifen in treating hormone-responsive breast cancer.
PURPOSE: This randomized phase III trial is studying triptorelin and exemestane to see how well they work compared to triptorelin and tamoxifen in treating premenopausal women with hormone-responsive breast cancer.
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OBJECTIVES:
- Compare the disease-free survival, breast cancer-free interval, distant recurrence-free interval and overall survival of premenopausal women with endocrine-responsive breast cancer when treated with triptorelin and exemestane vs triptorelin and tamoxifen.
- Compare the quality of life, including late side effects of early menopause, of patients treated with these regimens.
OUTLINE: This is a randomized, international, multicenter study. Patients are stratified according to planned use of concurrent adjuvant chemotherapy (yes vs no), and number of positive lymph nodes (0 vs 1 or more). Treatment duration is 5 years. Patients are followed every 3 months for 1 year, every 6 months for 5 years, and then annually thereafter. Quality of life is assessed at baseline, every 6 months for 2 years, and annually for 3 years.
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Interventional
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Phase 3
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Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment
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Breast Cancer
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- Drug: exemestane
Other Name: Aromasin
- Drug: tamoxifen
Other Name: Nolvadex
- Drug: triptorelin
Other Names:
- GnRH analogue
- Trelstar Depot
- Decapeptyl Depot
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- Active Comparator: T+OFS
Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus tamoxifen 20mg orally daily for 5 years. Tamoxifen (T) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.
Interventions:
- Drug: tamoxifen
- Drug: triptorelin
- Experimental: E+OFS
Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus exemestane 25mg orally daily for 5 years. Exemestane (E) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.
Interventions:
- Drug: exemestane
- Drug: triptorelin
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- Francis P, Fleming G, Nasi ML, et al.: Tailored treatment investigations for premenopausal women with endocrine responsive (ER+ and/or PGR+) breast cancer: the SOFT, TEXT, and PERCHE trials. [Abstract] The Breast 12 (Suppl 1): A-P104, S44, 2003.
- Regan MM, Pagani O, Walley B, Torrisi R, Perez EA, Francis P, Fleming GF, Price KN, Thurlimann B, Maibach R, Castiglione-Gertsch M, Coates AS, Goldhirsch A, Gelber RD; SOFT/TEXT/PERCHE Steering Committee and the International Breast Cancer Study Group. Premenopausal endocrine-responsive early breast cancer: who receives chemotherapy? Ann Oncol. 2008 Jul;19(7):1231-1241. doi: 10.1093/annonc/mdn037. Epub 2008 Mar 5.
- Rabaglio M, Ruepp B; Soft/Text/Perche Steering Committee. Death due to liver failure during endocrine therapy for premenopausal breast cancer. Acta Oncol. 2010 Aug;49(6):874-6. doi: 10.3109/0284186X.2010.484813. No abstract available.
- Regan MM, Pagani O, Fleming GF, Walley BA, Price KN, Rabaglio M, Maibach R, Ruepp B, Coates AS, Goldhirsch A, Colleoni M, Gelber RD, Francis PA; International Breast Cancer Study; GroupSOFT and TEXT Investigators. Adjuvant treatment of premenopausal women with endocrine-responsive early breast cancer: design of the TEXT and SOFT trials. Breast. 2013 Dec;22(6):1094-100. doi: 10.1016/j.breast.2013.08.009. Epub 2013 Oct 2.
- Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Lang I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE Jr, Pinotti G, Puglisi F, Crivellari D, Ruhstaller T, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Bernhard J, Luo W, Ribi K, Viale G, Coates AS, Gelber RD, Goldhirsch A, Francis PA; TEXT and SOFT Investigators; International Breast Cancer Study Group. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014 Jul 10;371(2):107-18. doi: 10.1056/NEJMoa1404037. Epub 2014 Jun 1.
- Pagani O, Walley BA, Fleming GF, Colleoni M, Lang I, Gomez HL, Tondini C, Burstein HJ, Goetz MP, Ciruelos EM, Stearns V, Bonnefoi HR, Martino S, Geyer CE Jr, Chini C, Puglisi F, Spazzapan S, Ruhstaller T, Winer EP, Ruepp B, Loi S, Coates AS, Gelber RD, Goldhirsch A, Regan MM, Francis PA; SOFT and TEXT Investigators and the International Breast Cancer Study Group (a division of ETOP IBCSG Partners Foundation). Adjuvant Exemestane With Ovarian Suppression in Premenopausal Breast Cancer: Long-Term Follow-Up of the Combined TEXT and SOFT Trials. J Clin Oncol. 2023 Mar 1;41(7):1376-1382. doi: 10.1200/JCO.22.01064. Epub 2022 Dec 15.
- Pagani O, Francis PA, Fleming GF, Walley BA, Viale G, Colleoni M, Lang I, Gomez HL, Tondini C, Pinotti G, Di Leo A, Coates AS, Goldhirsch A, Gelber RD, Regan MM; SOFT and TEXT Investigators and International Breast Cancer Study Group. Absolute Improvements in Freedom From Distant Recurrence to Tailor Adjuvant Endocrine Therapies for Premenopausal Women: Results From TEXT and SOFT. J Clin Oncol. 2020 Apr 20;38(12):1293-1303. doi: 10.1200/JCO.18.01967. Epub 2019 Oct 16.
- Francis PA, Pagani O, Fleming GF, Walley BA, Colleoni M, Lang I, Gomez HL, Tondini C, Ciruelos E, Burstein HJ, Bonnefoi HR, Bellet M, Martino S, Geyer CE Jr, Goetz MP, Stearns V, Pinotti G, Puglisi F, Spazzapan S, Climent MA, Pavesi L, Ruhstaller T, Davidson NE, Coleman R, Debled M, Buchholz S, Ingle JN, Winer EP, Maibach R, Rabaglio-Poretti M, Ruepp B, Di Leo A, Coates AS, Gelber RD, Goldhirsch A, Regan MM; SOFT and TEXT Investigators and the International Breast Cancer Study Group. Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer. N Engl J Med. 2018 Jul 12;379(2):122-137. doi: 10.1056/NEJMoa1803164. Epub 2018 Jun 4.
- Regan MM, Walley BA, Francis PA, Fleming GF, Lang I, Gomez HL, Colleoni M, Tondini C, Pinotti G, Salim M, Spazzapan S, Parmar V, Ruhstaller T, Abdi EA, Gelber RD, Coates AS, Goldhirsch A, Pagani O. Concurrent and sequential initiation of ovarian function suppression with chemotherapy in premenopausal women with endocrine-responsive early breast cancer: an exploratory analysis of TEXT and SOFT. Ann Oncol. 2017 Sep 1;28(9):2225-2232. doi: 10.1093/annonc/mdx285.
- Johansson H, Gray KP, Pagani O, Regan MM, Viale G, Aristarco V, Macis D, Puccio A, Roux S, Maibach R, Colleoni M, Rabaglio M, Price KN, Coates AS, Gelber RD, Goldhirsch A, Kammler R, Bonanni B, Walley BA; the TEXT principal investigators. Impact of CYP19A1 and ESR1 variants on early-onset side effects during combined endocrine therapy in the TEXT trial. Breast Cancer Res. 2016 Nov 8;18(1):110. doi: 10.1186/s13058-016-0771-8.
- Regan MM, Francis PA, Pagani O, Fleming GF, Walley BA, Viale G, Colleoni M, Lang I, Gomez HL, Tondini C, Pinotti G, Price KN, Coates AS, Goldhirsch A, Gelber RD. Absolute Benefit of Adjuvant Endocrine Therapies for Premenopausal Women With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer: TEXT and SOFT Trials. J Clin Oncol. 2016 Jul 1;34(19):2221-31. doi: 10.1200/JCO.2015.64.3171. Epub 2016 Apr 4.
- Bernhard J, Luo W, Ribi K, Colleoni M, Burstein HJ, Tondini C, Pinotti G, Spazzapan S, Ruhstaller T, Puglisi F, Pavesi L, Parmar V, Regan MM, Pagani O, Fleming GF, Francis PA, Price KN, Coates AS, Gelber RD, Goldhirsch A, Walley BA. Patient-reported outcomes with adjuvant exemestane versus tamoxifen in premenopausal women with early breast cancer undergoing ovarian suppression (TEXT and SOFT): a combined analysis of two phase 3 randomised trials. Lancet Oncol. 2015 Jul;16(7):848-58. doi: 10.1016/S1470-2045(15)00049-2. Epub 2015 Jun 16.
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Active, not recruiting
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2672
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Not Provided
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December 2025
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March 11, 2011 (Final data collection date for primary outcome measure)
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DISEASE CHARACTERISTICS:
- Histologically confirmed breast cancer
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Completely resected disease
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Tumor confined to the breast and axillary nodes
- Tumor detected in internal mammary chain nodes by sentinel node procedure and is not enlarged is allowed
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Axillary lymph node dissection or a negative axillary sentinel node biopsy required
- Patients with negative or microscopically positive axillary sentinel nodes are eligible
- Positive sentinel nodes must have either axillary dissection or radiation of axillary nodes
- No distant metastases
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No locally advanced inoperable breast cancer, including any of the following:
- Inflammatory breast cancer
- Supraclavicular node involvement
- Enlarged internal mammary nodes (unless pathologically negative)
- Bilateral synchronous invasive breast cancer allowed if disease meets all other eligibility criteria
- No prior ipsilateral or contralateral invasive breast cancer
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Hormone receptor status:
PATIENT CHARACTERISTICS:
Age
Sex
Menopausal status
Performance status
Life expectancy
Hematopoietic
Hepatic
- No systemic hepatic disease that would preclude prolonged follow-up
Renal
- No systemic renal disease that would preclude prolonged follow-up
Cardiovascular
- No systemic cardiovascular disease that would preclude prolonged follow-up
- No prior thrombosis (e.g., deep vein thrombosis) and/or embolism unless patient is medically suitable
Pulmonary
- No systemic pulmonary disease that would preclude prolonged follow-up
Other
- Not pregnant or nursing
- Fertile patients must use effective nonhormonal contraception
- No history of noncompliance to medical regimens
- No other nonmalignant systemic disease that would preclude prolonged follow-up
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No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, nonbreast carcinoma in situ, contralateral or ipsilateral carcinoma in situ of the breast, or other nonrecurrent invasive nonbreast malignancy, including any of the following:
- Stage I papillary thyroid cancer
- Stage IA carcinoma of the cervix
- Stage IA or B endometrioid endometrial cancer
- Borderline or stage I ovarian cancer
- No psychiatric, addictive, or other disorder that would preclude study compliance
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Prior or concurrent neoadjuvant or adjuvant trastuzumab allowed
Chemotherapy
- No prior neoadjuvant or adjuvant chemotherapy
Endocrine therapy
- No prior tamoxifen, other selective estrogen-receptor modulators (SERMs) (e.g., raloxifene), or hormone replacement therapy for more than 1 year before breast cancer diagnosis
- No prior neoadjuvant or adjuvant endocrine therapy since diagnosis of breast cancer
- No concurrent oral or transdermal hormonal therapy
- No other concurrent estrogen, progesterone, or androgens
- No other concurrent aromatase inhibitors
- No concurrent oral or other hormonal contraceptives (i.e., implants or depot injections)
Radiotherapy
- See Disease Characteristics
- No prior ovarian radiotherapy
Surgery
- See Disease Characteristics
- No prior bilateral oophorectomy
Other
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Sexes Eligible for Study: |
Female |
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18 Years to 65 Years (Adult, Older Adult)
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No
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Contact information is only displayed when the study is recruiting subjects
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Australia, Belgium, Brazil, Canada, Egypt, Germany, Hungary, India, Italy, New Zealand, Peru, Slovenia, South Africa, Sweden, Switzerland, United Kingdom, United States
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NCT00066703
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IBCSG 25-02 / BIG 3-02 IBCSG 25-02 BIG 3-02 ( Other Identifier: Breast International Group ) NABCI IBCSG 25-02 EU-20347 2004-000168-28 ( EudraCT Number ) CDR0000316458 ( Registry Identifier: CT.gov )
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Yes
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Not Provided
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Not Provided
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ETOP IBCSG Partners Foundation
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Not Provided
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ETOP IBCSG Partners Foundation
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Same as current
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- National Cancer Institute (NCI)
- Breast International Group
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Study Chair: |
Olivia Pagani, MD |
Oncology Institute of Southern Switzerland |
Study Chair: |
Barbara Walley, MD, FRCPC |
Tom Baker Cancer Centre |
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ETOP IBCSG Partners Foundation
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December 2023
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