SOLE: Study Of Letrozole Extension in post-menopausal women with breast cancer

ISRCTN	ISRCTN43286545
DOI	https://doi.org/10.1186/ISRCTN43286545
ClinicalTrials.gov (NCT)	NCT00553410
Clinical Trials Information System (CTIS)	2007-001370-88
Protocol serial number	IBCSG 35-07/BIG 1-07
Sponsor	European Institute of Oncology (IEO) (Italy)
Funder	International Breast Cancer Study Group (UK) - funding for UK arm of trial

Submission date: 02/09/2009
Registration date: 03/11/2009
Last edited: 27/07/2022

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

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-letrozole-after-hormone-therapy-early-breast-cancer-postmenopausal-women

Contact information

Prof Alastair Thompson
Scientific

Professor of Surgical Oncology
University of Dundee
Ninewells Hospital & Medical School
Dundee
DD1 9SY
United Kingdom

Phone	+44 (0)1382 633936
Email	a.m.thompson@dundee.ac.uk

Study information

Primary study design	Interventional
Study design	Randomised controlled phase III trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	A phase III trial evaluating the role of continuous letrozole versus intermittent letrozole following 4 to 6 years of prior adjuvant endocrine therapy for post-menopausal women with hormone-receptor positive, node positive early stage breast cancer
Study acronym	SOLE
Study objectives	In 2006, the standard duration of adjuvant endocrine therapy for breast cancer (either selective estrogen receptor modulators [SERMs] or aromatase inhibitor [AI]) is five years. Patients who receive extended adjuvant letrozole for five years following approximately five years of tamoxifen obtain further benefit compared with the five years of tamoxifen alone. Similarly, benefit has been demonstrated for switching from tamoxifen to an AI after 2 to 3 years of tamoxifen to complete five years of endocrine therapy, as well as initiating therapy with AI following surgery and administering the AI for five years. Questions remain about the optimal duration and best schedule of AIs in the extended adjuvant setting. This trial tests the hypothesis that introducing 3-month treatment-free intervals during the course of five years of extended adjuvant letrozole will improve disease-free survival. This hypothesis is based on the theoretical principle that letrozole withdrawal for 3 months will permit some estrogenic stimulation which makes residual resistant disease susceptible to letrozole reintroduction.
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Breast cancer
Intervention	Arm A - Continuous letrozole 2.5 mg daily for 5 years Arm B - Intermittent letrozole 2.5 mg daily for first 9 months of years 1 through 4, followed by 12 months in year 5
Intervention type	Drug
Phase	Phase III
Drug / device / biological / vaccine name(s)	Letrozole
Primary outcome measure(s)	Disease-free survival (DFS) is defined as the time from randomisation to local (including invasive recurrence restricted to the breast after breast conserving treatment), regional or distant relapse, contralateral breast cancer, appearance of a second (non-breast) malignancy, or death from any cause, whichever occurs first. Appearance of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) either in the ipsilateral or in the contralateral breast will not be considered as an event for DFS. Event driven analyses - final analysis requires 647 events, interim analysis at 259 and 453 events.
Key secondary outcome measure(s)	1. Overall survival (OS) is defined as the time from randomisation to death from any cause 2. Distant disease-free survival (DDFS) is defined as the time from randomisation to any recurrent or metastatic disease in distant sites (i.e., other than the local mastectomy scar/chest wall/skin, the ipsilateral breast in case of breast conservation, or the ipsilateral axilla and internal mammary lymph nodes), second (non-breast) malignancy, or death from any cause, whichever occurs first 3. Breast cancer free interval (BCFI) is defined as the time from randomisation to local (including recurrence restricted to the breast after breast conserving treatment), regional, or distant relapse, or contralateral breast cancer. In calculating BCFI, second (non-breast) malignancies are ignored and deaths without cancer event are censored at the time of death as a competing event. Appearance of DCIS or LCIS either in the ipsilateral or in the contralateral breast is not considered a BCFI event, but should be recorded on the Follow-up Form (E) 4. Sites of first DFS failure 5. Second (non-breast) malignancies 6. Deaths without prior cancer event 7. Adverse events Event driven analyses - final analysis requires 647 events, interim analysis at 259 and 453 events.
Completion date	31/12/2018

Eligibility

Participant type(s)	Patient
Age group	Other
Sex	Female
Target sample size at registration	4800
Total final enrolment	4884
Key inclusion criteria	1. Patients must be post-menopausal; definitive confirmation of post-menopausal status is required 2. Patients must be accessible for follow-up 3. At diagnosis, patients must have had operable, non-inflammatory breast cancer 4. Patients must be clinically disease-free at randomisation 5. Patients must have had steroid hormone receptor positive tumours (oestrogen receptor [ER] and/or progesterone receptor [PgR]), determined by immunohistochemistry, after primary surgery and before commencement of prior endocrine therapy 6. Following primary surgery, eligible patients must have had evidence of lymph node involvement either in the axillary or internal mammary nodes, but not supraclavicular nodes 7. There must have been no evidence of recurrent disease or distant metastatic disease at any time prior to randomisation 8. Patients must have had proper local treatment including surgery with or without radiotherapy for primary breast cancer with no known clinical residual loco-regional disease 9. Patients must have clinically adequate hepatic function 10. Patients must have completed 4 to 6 years of prior adjuvant endocrine therapy with SERMs, AI or a sequential combination of both. When calculating 4 - 6 years, neoadjuvant endocrine therapy should not be included. 11. Patients must have stopped prior endocrine SERM/AI therapy, and must be randomized within 12 months (1 year) of the last dose of prior endocrine SERM/AI therapy 12. Patients may have received any type of prior adjuvant therapy, including but not limited to neoadjuvant chemotherapy, neoadjuvant endocrine therapy, adjuvant chemotherapy, trastuzumab, ovarian ablation, GnRH analogues, lapatinib 13. Patients must have stopped hormone replacement therapy (HRT), bisphosphonates (except for treatment of bone loss), or any investigational agent at randomisation 14. Pathology material from the primary tumour must be available for submission for central review as part of the quality control measures for this protocol 15. Written informed consent (IC) must be signed and dated by the patient and the investigator prior to randomisation 16. Written consent to pathology material submission, indicating the patient has been informed of and agrees to tissue material use, transfer and handling, must be signed and dated by the patient and the investigator prior to randomisation 17. Females, no defined age limits
Key exclusion criteria	1. Patients who have had bilateral breast cancer 2. Patients who have had a bone fracture due to osteoporosis at any time during the 4-6 years of prior endocrine SERM/AI therapy 3. Patients who have had any previous or concomitant malignancy EXCEPT adequately treated: basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, contra- or ipsilateral in situ breast carcinoma 4. Patients who have had any other non-malignant systemic diseases (cardiovascular, renal, lung, etc.) that would prevent prolonged follow-up 5. Patients with psychiatric, addictive, or any disorder which compromises compliance with protocol requirements
Date of first enrolment	01/11/2007
Date of final enrolment	08/10/2012

Locations

Countries of recruitment

United Kingdom
Scotland
Australia
Belgium
Chile
Denmark
Germany
Hungary
Italy
New Zealand
Peru
South Africa
Sweden
Switzerland

Study participating centre

University of Dundee

Dundee
DD1 9SY
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
IPD sharing plan	The data sharing plans for the study are currently unknown and will be made available at a later date

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/01/2018	10/09/2019	Yes	No
Basic results			10/09/2019	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Plain English results			27/07/2022	No	Yes

Editorial Notes

27/07/2022: Cancer Research UK plain English results summary link and total final enrolment added.
10/09/2019: ClinicalTrials.gov number and EudraCT number added. Publication reference added. Added ClinicalTrials.gov link to basic results (scientific).
22/07/2019: IPD sharing statement added.
19/07/2019: The following changes were made to the trial record:
1. The overall trial end date was changed from 01/11/2021 to 31/12/2018.
2. The recruitment end date and intention to publish date were added.