August 6, 2003
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August 7, 2003
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July 14, 2015
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September 22, 2016
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January 2, 2024
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December 17, 2003
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May 2014 (Final data collection date for primary outcome measure)
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Disease-free Survival [ Time Frame: 5-year estimates, reported at a median follow-up of 67 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 estimates, reported at a median follow-up of 67 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 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 67 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 invasive breast cancer recurrence at distant site, or invasive contralateral breast cancer; or censored at date of last follow up.
- Overall Survival [ Time Frame: 8-year estimates, reported at a median follow-up of 8 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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Suppression of Ovarian Function With Either Tamoxifen or Exemestane Compared With Tamoxifen Alone in Treating Premenopausal Women With Hormone-Responsive Breast Cancer
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A Phase III Trial Evaluating the Role of Ovarian Function Suppression and the Role of Exemestane as Adjuvant Therapies for Premenopausal Women With Endocrine Responsive Breast Cancer
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RATIONALE: Estrogen can stimulate the growth of breast tumor cells. Ovarian function suppression combined with hormone therapy using tamoxifen or exemestane may fight breast cancer by reducing the production of estrogen. It is not yet known whether suppression of ovarian function plus either tamoxifen or exemestane is more effective than tamoxifen alone in preventing the recurrence of hormone-responsive breast cancer.
PURPOSE: This randomized phase III trial studies ovarian suppression with either tamoxifen or exemestane to see how well they work compared to tamoxifen alone in treating premenopausal women who have undergone surgery for 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 tamoxifen + ovarian function suppression (by triptorelin, oophorectomy, or ovarian irradiation) or exemestane + ovarian function suppression vs. tamoxifen alone. The primary comparison is ovarian function suppression with either tamoxifen or exemestane vs. tamoxifen alone.
- Compare the quality of life, including late side effects of early menopause, of patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, prior adjuvant/neoadjuvant chemotherapy (yes vs no), and number of positive axillary and/or internal mammary lymph nodes (0 vs 1 or more) and intended initial method of ovarian function suppression (triptorelin vs oophorectomy vs ovarian irradiation). 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 then annually for 4 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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- Estrogen Receptor Positive Breast Cancer
- Progesterone Receptor Positive Tumor
- Recurrent Breast Carcinoma
- Stage IA Breast Cancer
- Stage IB Breast Cancer
- Stage IIA Breast Cancer
- Stage IIB Breast Cancer
- Stage IIIA Breast Cancer
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- Drug: Exemestane
Exemestane 25mg orally daily for 5 years plus ovarian function suppression
- Other: Laboratory Biomarker Analysis
Correlative studies
- Procedure: Oophorectomy
Undergo bilateral surgical oophorectomy
Other Names:
- Female Castration
- Ovariectomy
- Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
- Radiation: Radiation Therapy
Undergo ovarian irradiation
Other Names:
- Cancer Radiotherapy
- Irradiate
- Irradiated
- Irradiation
- RADIATION
- Radiotherapeutics
- Radiotherapy
- RT
- Therapy, Radiation
- Drug: Tamoxifen
Tamoxifen 20mg orally daily for 5 years
Other Names:
- Apo-Tamox
- Clonoxifen
- Dignotamoxi
- Ebefen
- Emblon
- Estroxyn
- Fentamox
- Gen-Tamoxifen
- Genox
- ICI 46,474
- ICI-46474
- Jenoxifen
- Kessar
- Ledertam
- Lesporene
- Nolgen
- Noltam
- Nolvadex
- Nolvadex-D
- Nourytam
- Novo-Tamoxifen
- Novofen
- Noxitem
- Oestrifen
- Oncotam
- PMS-Tamoxifen
- Soltamox
- TAM
- Tamax
- Tamaxin
- Tamifen
- Tamizam
- Tamofen
- Tamoxasta
- TAMOXIFEN CITRATE
- Tamoxifeni Citras
- Zemide
- Drug: Triptorelin
3.75 mg by im injection q28 days for 5 years
Other Names:
- 6-D-Tryptophan-LH-RH
- 6-D-Tryptophanluteinizing Hormone-releasing Factor
- AY-25650
- CL-118,532
- Decapeptyl
- Detryptoreline
- GnRH analogue
- Trelstar Depot
- Decapeptyl Depot
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- Active Comparator: Tamoxifen
Tamoxifen 20mg orally daily for 5 years
Interventions:
- Other: Laboratory Biomarker Analysis
- Other: Quality-of-Life Assessment
- Drug: Tamoxifen
- Experimental: T+OFS
Tamoxifen 20mg orally daily for 5 years plus ovarian function suppression (OFS; triptorelin (GnRH analogue) 3.75 mg by im injection q28 days for 5 years; or surgical oophorectomy; or ovarian irradiation)
Interventions:
- Other: Laboratory Biomarker Analysis
- Procedure: Oophorectomy
- Other: Quality-of-Life Assessment
- Radiation: Radiation Therapy
- Drug: Tamoxifen
- Drug: Triptorelin
- Experimental: E+OFS
Exemestane 25mg orally daily for 5 years plus ovarian function suppression (OFS; triptorelin (GnRH analogue) 3.75 mg by im injection q28 days for 5 years; or surgical oophorectomy; or ovarian irradiation)
Interventions:
- Drug: Exemestane
- Other: Laboratory Biomarker Analysis
- Procedure: Oophorectomy
- Other: Quality-of-Life Assessment
- Radiation: Radiation Therapy
- Drug: Triptorelin
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- Francis PA, Regan MM, Fleming GF, Lang I, Ciruelos E, Bellet M, Bonnefoi HR, Climent MA, Da Prada GA, Burstein HJ, Martino S, Davidson NE, Geyer CE Jr, Walley BA, Coleman R, Kerbrat P, Buchholz S, Ingle JN, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Colleoni M, Viale G, Coates AS, Goldhirsch A, Gelber RD; SOFT Investigators; International Breast Cancer Study Group. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015 Jan 29;372(5):436-46. doi: 10.1056/NEJMoa1412379. Epub 2014 Dec 11.
- Francis PA, Fleming GF, Lang I, Ciruelos EM, Bonnefoi HR, Bellet M, Bernardo A, Climent MA, Martino S, Bermejo B, Burstein HJ, Davidson NE, Geyer CE Jr, Walley BA, Ingle JN, Coleman RE, Muller B, Le Du F, Loibl S, Winer EP, Ruepp B, Loi S, Colleoni M, Coates AS, Gelber RD, Goldhirsch A, Regan MM; SOFT Investigators and the International Breast Cancer Study Group (a division of ETOP IBCSG Partners Foundation). Adjuvant Endocrine Therapy in Premenopausal Breast Cancer: 12-Year Results From SOFT. J Clin Oncol. 2023 Mar 1;41(7):1370-1375. doi: 10.1200/JCO.22.01065. Epub 2022 Dec 9. Erratum In: J Clin Oncol. 2023 Sep 1;41(25):4187.
- 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.
- 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.
- Ribi K, Luo W, Bernhard J, Francis PA, Burstein HJ, Ciruelos E, Bellet M, Pavesi L, Lluch A, Visini M, Parmar V, Tondini C, Kerbrat P, Perello A, Neven P, Torres R, Lombardi D, Puglisi F, Karlsson P, Ruhstaller T, Colleoni M, Coates AS, Goldhirsch A, Price KN, Gelber RD, Regan MM, Fleming GF. Adjuvant Tamoxifen Plus Ovarian Function Suppression Versus Tamoxifen Alone in Premenopausal Women With Early Breast Cancer: Patient-Reported Outcomes in the Suppression of Ovarian Function Trial. J Clin Oncol. 2016 May 10;34(14):1601-10. doi: 10.1200/JCO.2015.64.8675. Epub 2016 Mar 28.
- 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.
- 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.
- 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.
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Active, not recruiting
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3066
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Not Provided
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December 2025
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May 2014 (Final data collection date for primary outcome measure)
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Inclusion Criteria:
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Premenopausal women (estradiol [E2] in the premenopausal range [according to institution parameters]) who meet the following criteria:
- Patients who did not receive chemotherapy should be randomized within 12 weeks after definitive surgery; such patients should have estradiol (E2) in the premenopausal range following surgery; the only patients who do not require testing of estradiol (E2) to confirm premenopausal status are those who have been menstruating regularly during the 6 months prior to randomization and have not used any form of hormonal contraception or any other hormonal treatments during the 6 months prior to randomization
- Patients who received prior adjuvant and/or neoadjuvant chemotherapy should be randomized after completing chemotherapy and within 8 months of the final dose of chemotherapy as soon as premenopausal status is confirmed; all such patients should have premenopausal status confirmed by an estradiol (E2) in the premenopausal range between 2 weeks and 8 months after completing chemotherapy
- Adjuvant trastuzumab (Herceptin ®) is allowable, and is not considered to be chemotherapy for eligibility timing determination
- Patients with temporary chemotherapy-induced amenorrhea who regain premenopausal status within eight months of the final dose of chemotherapy are eligible; (please note that some patients taking tamoxifen or aromatase inhibitors, even without evidence of menses, may have ovarian function recovery following chemotherapy and resume estradiol secretion); in patients wishing to participate in the study, with postmenopausal hormone levels shortly after chemotherapy, it is recommended to recheck their estradiol level at a later timepoint within 8 months of completing chemotherapy, even in the absence of return of menses
- Histologically proven, resected breast cancer; pathology material should be available for submission for central review as part of the quality control measures for this protocol
- Patients must have hormone receptor positive tumors; if there is more than one breast tumor, each tumor must be hormone receptor positive; hormone receptors must be determined using immunohistochemistry; estrogen receptor (ER) and/or progesterone receptor (PgR) must be greater than or equal to 10% of the tumor cells positive by immunohistochemical evaluation; biochemical determination alone is not acceptable
- The tumor must be confined to the breast and axillary nodes without detected metastases elsewhere, with the exception of tumor detected in internal mammary chain nodes by sentinel node procedure; patients who received neoadjuvant therapy must have had operable disease prior to neoadjuvant treatment to be eligible; patients who had a pathological evaluation with tru cut or core biopsy of invasive breast cancer prior to neoadjuvant therapy and were found to have no invasive tumor in the pathological specimen from definitive surgery are eligible; for these patients, pre-neoadjuvant tumor characteristics will be used for defining eligibility; in case of persistent disease, pathology findings from the definitive surgery should be used
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Patients must have had proper surgery for primary breast cancer with no known clinical residual loco-regional disease:
- A total mastectomy; radiotherapy is optional after mastectomy OR
- A breast-conserving procedure (lumpectomy, quadrantectomy or partial mastectomy with margins clear of invasive cancer and ductal breast carcinoma in situ [DCIS]); the local pathologist must document negative margins of resection in the pathology report; if all other margins are clear, a positive posterior (deep) margin is permitted, provided the surgeon documents that the excision was performed down to the pectoral fascia and all tumor has been removed; likewise, if all other margins are clear, a positive anterior (superficial; abutting skin) margin is permitted provided the surgeon documents that all tumor has been removed; radiation therapy to the conserved breast is required; patients may be randomized before, during or after completion of radiation therapy to the breast
- Either axillary lymph node dissection (pathological examination of at least 6 nodes recommended) or a negative axillary sentinel node biopsy (pN0[sn]) is required; patients with negative or microscopically axillary positive sentinel nodes (pN1mi: micrometastasis none > 2.0 mm) do not require further axillary therapy; those with positive sentinel nodes must have either an axillary dissection or radiation of axillary nodes
- For International Breast Cancer Study Groups (IBCSG) centers, patients must have completed baseline Quality of Life (QL) Forms prior to randomization; the only exceptions are cognitive or physical impairment that interferes with QL assessment or inability to read any of the languages available on IBCSG QL forms; for non-IBCSG centers, extent of participation in the QL study is to be determined at the activation of the trial for each cooperative group
- Written informed consent must be signed and dated by the patient and the investigator prior to randomization
- Patients must be accessible for follow-up
- Patients must be informed of and agree to data and tissue material transfer and handling, in accordance with national data protection guidelines
Exclusion Criteria:
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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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Canada, Switzerland, United States
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Australia, Brazil, Chile, Germany, Hungary, India, Italy, New Zealand, Peru, South Africa, Spain, Sweden, United Kingdom
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NCT00066690
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IBCSG 24-02 / BIG 2-02 NCI-2009-01086 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) CDR0000316456 BIG 2-02 2004-000166-13 IBCSG-24-02 ( Other Identifier: CTEP ) U24CA075362 ( U.S. NIH Grant/Contract )
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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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- Breast International Group
- Cancer and Leukemia Group B
- National Cancer Institute (NCI)
- NSABP Foundation Inc
- NCIC Clinical Trials Group
- North Central Cancer Treatment Group
- SWOG Cancer Research Network
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Principal Investigator: |
Gini Fleming |
ETOP IBCSG Partners Foundation |
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ETOP IBCSG Partners Foundation
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December 2023
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