Suppression of Ovarian Function Trial
| ISRCTN | ISRCTN73368402 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN73368402 |
| ClinicalTrials.gov (NCT) | NCT00066690 |
| Clinical Trials Information System (CTIS) | 2004-000166-13 |
| Protocol serial number | 1305 |
| Sponsor | European Institute of Oncology (IEO) (Italy) |
| Funders | Cancer Research UK (CRUK) (UK) (ref: C2232/A4595), International Breast Cancer Study Group (IBCSG) (UK) |
- Submission date
- 12/05/2010
- Registration date
- 12/05/2010
- Last edited
- 20/05/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Mr Mark Webster-Smith
Scientific
Scientific
Clinical Trials & Statistics Unit (ICR-CTSU)
Section of Clinical Trials
Brookes Lawley Building
15 Cotswold Road
Sutton
SM2 5NG
United Kingdom
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Multicentre randomized interventional treatment trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | A multicentre randomised interventional trial on the benefits of ovarian function suppression in pre-menopausal women with oestrogen receptor positive breast cancer |
| Study acronym | SOFT |
| Study objectives | Chemotherapy (CT), tamoxifen, and ovarian function suppression (OFS) are individually effective adjuvant treatment modalities in women under 50 with oestrogen receptor (ER) positive (tumours expressing the oestrogen receptor) breast cancer. Chemotherapy plus 5 years tamoxifen (a widely used treatment which blocks the action of oestrogen on the tumour) is more effective than chemotherapy alone, however it is unclear whether any additional benefit is derived from ovarian function suppression as no trial has addressed this question to date. This trial aims to focus the OFS question on the subset of women who biologically would be most likely to benefit. These are women with oestrogen receptor positive breast cancer who remain pre-menopausal following either surgery alone or after completion of chemotherapy. The majority of pre-menopausal women with breast cancer are at least 40, and more than 80% will develop amenorrhoea following 6 cycles of cyclophosphamide, methotrexate and fluorouracil 5FU (CMF) chemotherapy. By contrast, less than half of pre-menopausal women under the age of 40 develop amenorrhoea with CMF. The prognosis of women who develop amenorrhoea tends to be better than those who continue to menstruate. Consequently the women in this trial will generally be younger than the median age for pre-menopausal breast cancer and will most likely be under 40. |
| Ethics approval(s) | South West Multi-centre Research Ethics Committee, 04/08/2004, ref: 04/Q1605/20 |
| Health condition(s) or problem(s) studied | Topic: National Cancer Research Network; Subtopic: Breast Cancer; Disease: Breast |
| Intervention | 1. Tamoxifen for 5 years 2. OFS** plus tamoxifen for 5 years 3. OFS** plus exemestane for 5 years (** OFS = ovarian function suppression (triptorelin for 5 years OR surgical oophorectomy OR ovarian irradiation)) Radiotherapy: Radiation therapy to the conserved breast is required. Radiation therapy to the chest wall following mastectomy is optional (if given, it may also include nodal fields). Radiation therapy may be given either after all chemotherapy or integrated into chemotherapy. Follow up length: 120 months Study entry: registration and one or more randomisations |
| Intervention type | Drug |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Tamoxifen, exemestane, triptorelin |
| Primary outcome measure(s) | To compare ovarian function suppression (OFS: GnRH analogue or oophorectomy) |
| Key secondary outcome measure(s) | 1. Overall survival 2. Systemic disease-free survival 3. Quality of life 4. Sites of first treatment failure |
| Completion date | 21/02/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Female |
| Target sample size at registration | 3000 |
| Total final enrolment | 3066 |
| Key inclusion criteria | 1. Pre-menopausal women (estradiol [E2] levels in the pre-menopausal range) either after chemotherapy or without chemotherapy 2. Randomisation within an 8-month evaluation period after end of CT, or within 12 weeks after definitive surgery for patients with no CT. Patients with temporary chemotherapy-induced amenorrhoea who regain pre-menopausal status within 6 months of the final chemotherapy dose are eligible. 3. Histologically proven, resected breast cancer. Pathology material available for submission for central review. 4. Hormone receptor (HR) positive tumour. HR must be determined using immunohistochemistry (IHC): ER and/or progesterone receptor (PgR) greater than or equal to 10% 5. Tumour confined to the breast and axillary nodes without detected metastases elsewhere with the exception of tumour detected in the internal mammary chain nodes by sentinel node procedure 6. Proper surgery (total mastectomy or breast conserving procedure plus radiation) for primary disease with no known clinical residual disease 7. Axillary lymph node dissection or negative axillary sent |
| Key exclusion criteria | 1. Post-menopausal 2. Distant metastatic disease 3. Locally advanced inoperable breast cancer 4. Bilateral invasive breast cancer 5. Positive final margins 6. Clinically detectable residual axillary disease 7. History of previous ipsilateral or contralateral invasive breast cancer 8. Previous or concomitant malignancy except adequately treated basal/squamous cell carcinoma of the skin, in-situ carcinoma of the cervix or bladder, contralateral or ipsilateral in-situ breast cancer 9. Other non-malignant systemic diseases that would prevent prolonged follow-up 10. Patients who have had a bilateral oophorectomy or ovarian irradiation or are planning oophorectomy within 5 years 11. History of noncompliance to medical regimens or considered potentially unreliable 12. Patients who are pregnant or lactating at randomisation or who desire a pregnancy within 5 years. Patients planning to use additional hormone therapy (including contraceptives) during the next 5 years 13. Previous endocrine therapy (neoadjuvant/adjuvant) |
| Date of first enrolment | 17/12/2003 |
| Date of final enrolment | 30/04/2010 |
Locations
Countries of recruitment
- United Kingdom
- England
- Australia
- Belgium
- Canada
- Egypt
- Germany
- Hungary
- India
- Italy
- New Zealand
- Peru
- Slovenia
- South Africa
- Sweden
- Switzerland
- United States of America
Study participating centre
Clinical Trials & Statistics Unit (ICR-CTSU)
Sutton
SM2 5NG
United Kingdom
SM2 5NG
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/09/2017 | 28/02/2019 | Yes | No |
| Results article | results | 01/07/2015 | 28/02/2019 | Yes | No |
| Results article | results | 01/07/2016 | 28/02/2019 | Yes | No |
| Results article | results | 10/07/2014 | 28/02/2019 | Yes | No |
| Results article | results | 10/05/2016 | 28/02/2019 | Yes | No |
| Results article | results | 12/07/2018 | 28/02/2019 | Yes | No |
| Results article | results | 29/01/2015 | 28/02/2019 | Yes | No |
| Protocol article | protocol | 01/12/2013 | 28/02/2019 | Yes | No |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Plain English results | No | Yes | |||
| Study website | Study website | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
20/05/2024: Total final enrolment added. The overall study end date was changed from 30/04/2010 to 21/02/2024.
28/02/2019: Publication references added.
19/10/2018: Cancer Research UK lay results summary link added to Results (plain English)
08/04/2016: No publications found, verifying study status with principal investigator.
