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Trial · Interventional

CompletedPhase 3Results postedRegistry data

Suppression of Ovarian Function With Either Tamoxifen or Exemestane Compared With Tamoxifen Alone in Treating Premenopausal Women With Hormone-Responsive Breast Cancer

Short name SOFT

NCTNCT00066690 (opens ClinicalTrials.gov in a new tab)Other idIBCSG 24-02 / BIG 2-02Other idNCI-2009-01086Other idCDR0000316456Other idBIG 2-02

Overview

Status
Completed
Phase
Phase 3
Enrollment
3,066 participants (actual)
Sponsor
ETOP IBCSG Partners Foundation · Network
Design
Randomized · Open label (no masking)
Countries
3 countries

United States, Canada, Switzerland

Start
17 Dec 2003
Primary completion
May 2014
Completion
6 Nov 2024
First posted
7 Aug 2003 (estimated)
Last update posted
26 Aug 2026
Conditions
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

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20052010201520202025
  1. Ph 3

    SOFT

    NCT00066690

    17 Dec 2003 to 6 Nov 2024

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • ExemestaneDrug
  • Laboratory Biomarker AnalysisOther
  • OophorectomyProcedure
  • Quality-of-Life AssessmentOther
  • Radiation TherapyRadiation
  • TamoxifenDrug
  • TriptorelinDrug

Arms3

  • Active comparator

    Tamoxifen

    Tamoxifen 20mg orally daily for 5 years

  • 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)

  • 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)

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Disease-free Survival

    Time frame · 5-year estimates, reported at a median follow-up of 67 months.

    Registry description

    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.

Secondary outcomes(3)
  1. Breast Cancer-free Interval

    Time frame · 5-year estimates, reported at a median follow-up of 67 months.

    Registry description

    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.

  2. Distant Recurrence-free Interval

    Time frame · 5-year estimates, reported at a median follow-up of 67 months.

    Registry description

    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.

  3. Overall Survival

    Time frame · 8-year estimates, reported at a median follow-up of 8 years

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeNumber· 5-year estimates, reported at a median follow-up of 67 months.

Disease-free Survival

GroupValue (percentage of participants)
Tamoxifen84.7
T+OFS86.6
E+OFS89
Secondary and other outcome results(3)
Secondary outcomeNumber· 5-year estimates, reported at a median follow-up of 67 months.

Breast Cancer-free Interval

GroupValue (percentage of participants)
Tamoxifen86.4
T+OFS88.4
E+OFS90.9
Secondary outcomeNumber· 5-year estimates, reported at a median follow-up of 67 months.

Distant Recurrence-free Interval

GroupValue (percentage of participants)
Tamoxifen90.7
T+OFS91.3
E+OFS93.0
Secondary outcomeNumber· 8-year estimates, reported at a median follow-up of 8 years

Overall Survival

GroupValue (percentage of participants)
Tamoxifen91.5
T+OFS93.3
E+OFS92.1

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
TamoxifenTamoxifen 20mg orally daily for 5 years87 / 1007315 / 1007951 / 1007
T+OFSTamoxifen 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)68 / 1007375 / 1007982 / 1007
E+OFSExemestane 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)80 / 1001375 / 1001980 / 1001

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies3

Studies that cite this trial.

Studies with results

0 studies on this page

Indexing hint: Randomized controlled trial · 2017

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.

Regan et al. 2017Annals of oncology : official journal of the European Society for Medical Oncologycited by 52

PMID 28911092PMC5834112DOI 10.1093/annonc/mdx285PUB-28911092

Rights unknown
Source link

Indexing hint: Randomized controlled trial · 2015

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.

Bernhard et al. 2015The Lancet. Oncologycited by 138

PMID 26092816PMC4562429DOI 10.1016/s1470-2045(15)00049-2PUB-26092816

Rights unknown
Source link

Indexing hint: Randomized controlled trial · 2014

Adjuvant exemestane with ovarian suppression in premenopausal breast cancer.

Pagani et al. 2014The New England journal of medicinecited by 530

PMID 24881463PMC4175521DOI 10.1056/nejmoa1404037PUB-24881463

Rights unknown
Source link

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • ResultFrancis 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. PMID 25495490
  • ResultFrancis 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. PMID 36493334
  • DerivedO'Regan RM, Ren Y, Zhang Y, Fleming GF, Francis PA, Pagani O, Walley BA, Kammler R, Dell'Orto P, Viale G, Loi S, Colleoni M, Treuner K, Regan MM. Identifying premenopausal patients with early-stage hormone receptor-positive breast cancer at minimal risk of distant recurrence by breast cancer index. Breast. 2026 Apr;86:104714. doi: 10.1016/j.breast.2026.104714. Epub 2026 Jan 29. PMID 41637791
  • DerivedRibi K, Cole BF, Fleming GF, Walley BA, Francis PA, Abdi E, Burstein HJ, Cheng KL, Chia SKL, Dakhil SR, Davidson NE, Della-Fiorentina SA, Frith AE, Levine E, Lupichuk S, Pritchard K, Salim M, Stearns V, Stewart J, Valero V, van der Westhuizen A, Pagani O, Loi S, Colleoni M, Gelber RD, Goldhirsch A, Coates AS, Regan MM, Bernhard J. Prognostic value of patient-reported depression in women with hormone-responsive early breast cancer in TEXT and SOFT. Cancer. 2025 Oct 1;131(19):e70094. doi: 10.1002/cncr.70094. PMID 40986647
  • DerivedPagani 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. PMID 36521078
  • DerivedPagani 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. PMID 31618131
  • DerivedFrancis 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. PMID 29863451
  • DerivedRegan 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. PMID 27044936
  • DerivedRibi 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. PMID 27022111
  • DerivedRegan 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. PMID 24095609

Eligibility

Who could join, as posted.

Sex
Female
Age
from 18 Years up to 65 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * 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 * 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: * Patients who are postmenopausal (i.e., do not have an estradiol \[E2\] level in the premenopausal range) after surgery or after chemotherapy, whichever is later * Patients with distant metastatic disease * Patients with locally advanced inoperable breast cancer including inflammatory breast cancer or supraclavicular node involvement or with enlarged internal mammary nodes (unless pathologically negative) are not eligible; patients with involved internal mammary nodes detected by sentinel node biopsy that are not enlarged are eligible * Patients with positive final margins (referring to only DCIS and invasive cancer, not lobular breast carcinoma in situ \[LCIS\]), except as noted; DCIS at a margin is permitted if a complete mastectomy has been performed * Patients with clinically detectable residual axillary disease * Patients with a history of prior ipsilateral or contralateral invasive breast cancer; patients with synchronous bilateral invasive breast cancer (diagnosed histologically within 2 months) are eligible if the bilateral disease meets all other eligibility criteria * Patients with previous or concomitant invasive malignancy are not eligible; the exceptions are patients with the following (and only the following) malignancies (previous or concomitant) who are eligible if adequately treated: * Basal or squamous cell carcinoma of the skin * In situ non-breast carcinoma without invasion * Contra- or ipsilateral in situ breast carcinoma * Non-breast invasive malignancy diagnosed at least 5 years ago and without recurrence: * Stage I papillary thyroid cancer * Stage Ia carcinoma of the cervix * Stage Ia or b endometrioid endometrial cancer * Borderline or stage I ovarian cancer * Patients with other non-malignant systemic diseases (cardiovascular, renal, hepatic, lung, etc.) that would prevent prolonged follow-up; patients with previous thrombosis (e.g., deep vein thrombosis \[DVT\]) and/or embolism can be included only if medically suitable * Patients who have had a bilateral oophorectomy or ovarian irradiation; patients who will be recommended to undergo oophorectomy within 5 years (e.g., breast cancer susceptibility gene \[BRCA\]1/2 gene carriers) and therefore for whom randomization to a treatment arm without OFS is inappropriate * Patients with a history of noncompliance to medical regimens and patients who are considered potentially unreliable * Patients who are pregnant or lactating at the time of randomization or who desire a pregnancy within 5 years; patients planning to use additional hormonal therapy apart from the randomized treatment during the next five years including all types of hormonal contraception; a pregnancy test is recommended for women of child-bearing potential who are sexually active and not using reliable contraceptive methods * Patients who received endocrine therapy (including neoadjuvant and adjuvant) for more than 8 months after their breast cancer diagnosis; patients who are receiving endocrine therapy at randomization (and have received it for less than 8 months) may continue such therapy until protocol-specified tamoxifen/exemestane is initiated * Patients who were taking tamoxifen or other selective estrogen receptor modulator (SERM) (e.g. Raloxifene) or hormone replacement therapy (HRT) within one year prior to their breast cancer diagnosis; prior oral contraceptives are allowed * Patients who have received GnRH analogues as part of their breast cancer treatment prior to randomization * Patients with psychiatric, addictive, or any disorder that would prevent compliance with protocol requirements

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