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Trial registered on ANZCTR


Registration number
ACTRN12608000243314
Ethics application status
Approved
Date submitted
29/04/2008
Date registered
12/05/2008
Date last updated
15/01/2019
Date data sharing statement initially provided
15/01/2019
Date results information initially provided
15/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
IBCSG 35-07 / BIG 1-07 : Study of Letrozole Extension (SOLE). Letrozole in Preventing the Return of Cancer in Postmenopausal Women Who Have Received 4-6 Years of Hormone Therapy for Hormone Receptor-Positive, Lymph Node-Positive, Early-Stage Breast Cancer.
Scientific title
Postmenopausal women with hormone-receptor positive, node positive early breast cancer will have treatment with continuous letrozole compared with treatment with intermittent letrozole after 4 to 6 years of prior adjuvant endocrine treatment to see which is better at preventing the return of cancer.
Secondary ID [1] 554 0
NCT00553410 (ClinicalTrials.gov)
Secondary ID [2] 555 0
EUDRACT-2007-001370-88 (European Commission - European Clinical Trials Database)
Universal Trial Number (UTN)
Trial acronym
SOLE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Endocrine Responsive Breast Cancer 3084 0
Condition category
Condition code
Cancer 3241 3241 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study is designed to compare the following treament arms: A) Continuous oral letrozole 2.5mg daily for 5 years, and B) Intermittent oral letrozole 2.5mg daily for the first 9 months of years 1 through 4, followed by 12 months in year 5.
Intervention code [1] 2826 0
Treatment: Drugs
Comparator / control treatment
Continuous oral letrozole 2.5mg given daily for 5 years
Control group
Active

Outcomes
Primary outcome [1] 4124 0
Disease-free survival (DFS). DFS is defined as the time from randomisation to local, regional, or distant relapse, contralateral breast cancer, appearance of a second (non-breast) malignancy, or death from any cause, whichever occurs first.
Timepoint [1] 4124 0
Two interim and one final analyses are planned. The target number of events for the final analysis is 647, and interim analyses are planned after 40% and 70% information (259 and 453 events observed respectively).
Secondary outcome [1] 6941 0
Overall survival (OS). OS is defined as the time from randomisation to death from any cause.
Timepoint [1] 6941 0
The target number of events for the final analysis is 647, and interim analyses are planned after 40% and 70% information (259 and 453 events observed respectively).
Secondary outcome [2] 6942 0
Distant disease-free survival (DDFS). 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.
Timepoint [2] 6942 0
Two interim and one final analyses are planned. The target number of events for the final analysis is 647, and interim analyses are planned after 40% and 70% information (259 and 453 events observed respectively).
Secondary outcome [3] 6943 0
Breast Cancer Free Interval (BCFI). 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. Second (non-breast) malignancies are ignored and deaths without cancer event are censored at the time of death as a competing event.
Timepoint [3] 6943 0
Two interim and one final analyses are planned. The target number of events for the final analysis is 647, and interim analyses are planned after 40% and 70% information (259 and 453 events observed respectively).
Secondary outcome [4] 6944 0
Sites of first DFS failure
Timepoint [4] 6944 0
Two interim and one final analyses are planned. The target number of events for the final analysis is 647, and interim analyses are planned after 40% and 70% information (259 and 453 events observed respectively).
Secondary outcome [5] 6945 0
Second (non-breast) malignancies
Timepoint [5] 6945 0
Two interim and one final analyses are planned. The target number of events for the final analysis is 647, and interim analyses are planned after 40% and 70% information (259 and 453 events observed respectively).
Secondary outcome [6] 6946 0
Deaths without prior cancer event
Timepoint [6] 6946 0
Two interim and one final analyses are planned. The target number of events for the final analysis is 647, and interim analyses are planned after 40% and 70% information (259 and 453 events observed respectively).
Secondary outcome [7] 6947 0
Incidence of targeted adverse events
Timepoint [7] 6947 0
Two interim and one final analyses are planned. The target number of events for the final analysis is 647, and interim analyses are planned after 40% and 70% information (259 and 453 events observed respectively).

Eligibility
Key inclusion criteria
Patients must be postmenopausal. Have had operable, non-inflammatory breast cancer at diagnosis. Must be clinically disease-free at randomisation. Have had ER and/or PgR positive tumours after primary surgery and before commencement of prior endocrine therapy. Following primary surgery, patients must have had evidence of lymph node involvement either in the axillary or internal mammary nodes, but not supraclavicular nodes. Must have had proper local treatment including surgery with/without radiotherapy for primary breast cancer with no known clinical residual loco-regional disease. Patients must have clinically adequate hepatic function. Patients must have completed 4 to 6 years of prior adjuvant endocrine therapy with selective estrogen receptor modulators (SERM(s)), aromatase inhibitors(AI(s)), or a sequential combination of both (neoadjuvant endocrine therapy should not be included). Patients must have stopped prior endocrine SERM/AI therapy, and must be randomised within 12 months of the last dose of prior endocrine SERM/AI therapy. 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. Pathology material from the primary tumour must be available for submission for central review. Written Informed Consent, and written consent to pathology material submission. Must be accessible for follow-up.
Minimum age
No limit
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Evidence of recurrent disease or distant metastatic disease at any time prior to randomisation. Patients who have had bilateral breast cancer. Bone fracture due to osteoporosis at any time during the 4-6 years of prior SERM/AI therapy. 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. Other non-malignant systemic diseases (cardiovascular, renal, lung, etc.) that would prevent prolonged follow-up. Psychiatric, addictive, or any disorder which compromises compliance with protocol rquirements. Concurrent hormone replacement therapy, bisphosphonates (except for treatment of bone loss), or any investigational agent at randomisation.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated stratified blocks. Patients will be stratified according to the institution of recruitment and prior adjuvant endocrine therapy (AI(s) & SERM(s)): AI alone, SERM alone, both SERM and AI.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,QLD,WA,TAS
Recruitment postcode(s) [1] 663 0
2031
Recruitment postcode(s) [2] 661 0
2139
Recruitment postcode(s) [3] 660 0
2298
Recruitment postcode(s) [4] 664 0
2348
Recruitment postcode(s) [5] 659 0
2350
Recruitment postcode(s) [6] 662 0
2444
Recruitment postcode(s) [7] 665 0
2485
Recruitment postcode(s) [8] 671 0
3002
Recruitment postcode(s) [9] 668 0
3084
Recruitment postcode(s) [10] 669 0
3128
Recruitment postcode(s) [11] 670 0
3135
Recruitment postcode(s) [12] 672 0
6000
Recruitment postcode(s) [13] 673 0
6008
Recruitment postcode(s) [14] 674 0
6099
Recruitment postcode(s) [15] 667 0
7000
Recruitment postcode(s) [16] 666 0
7250
Recruitment outside Australia
Country [1] 952 0
New Zealand
State/province [1] 952 0
Christchurch
Country [2] 953 0
New Zealand
State/province [2] 953 0
Waikato

Funding & Sponsors
Funding source category [1] 3336 0
Self funded/Unfunded
Name [1] 3336 0
IBCSG (International Breast Cancer Study Group)
Address [1] 3336 0
IBCSG Coordinating Center
Effingerstrasse 40
CH- 3008 BERN
Country [1] 3336 0
Switzerland
Funding source category [2] 3337 0
Self funded/Unfunded
Name [2] 3337 0
BIG (Breast International Group)
Address [2] 3337 0
c/o Institut Jules Bordet
121 Blvd de Waterloo, 7th floor
B-1000 Brussels
Country [2] 3337 0
Belgium
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharma AG
Address
Lichtstrasse 35
4056 Basel
Country
Switzerland
Secondary sponsor category [1] 2982 0
None
Name [1] 2982 0
Address [1] 2982 0
Country [1] 2982 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5350 0
Hunter New England Health Service
Ethics committee address [1] 5350 0
Ethics committee country [1] 5350 0
Australia
Date submitted for ethics approval [1] 5350 0
28/04/2008
Approval date [1] 5350 0
26/08/2008
Ethics approval number [1] 5350 0
Ethics committee name [2] 5351 0
Royal Hobart Hospital
Ethics committee address [2] 5351 0
Ethics committee country [2] 5351 0
Australia
Date submitted for ethics approval [2] 5351 0
14/04/2008
Approval date [2] 5351 0
Ethics approval number [2] 5351 0
Ethics committee name [3] 5352 0
Launceston General Hospital
Ethics committee address [3] 5352 0
Ethics committee country [3] 5352 0
Date submitted for ethics approval [3] 5352 0
01/05/2008
Approval date [3] 5352 0
Ethics approval number [3] 5352 0
Ethics committee name [4] 5353 0
Austin Health
Ethics committee address [4] 5353 0
Ethics committee country [4] 5353 0
Australia
Date submitted for ethics approval [4] 5353 0
01/08/2008
Approval date [4] 5353 0
Ethics approval number [4] 5353 0
Ethics committee name [5] 5354 0
Box Hill Hospital
Ethics committee address [5] 5354 0
Ethics committee country [5] 5354 0
Australia
Date submitted for ethics approval [5] 5354 0
02/06/2008
Approval date [5] 5354 0
Ethics approval number [5] 5354 0
Ethics committee name [6] 5355 0
Maroondah Hospital
Ethics committee address [6] 5355 0
Ethics committee country [6] 5355 0
Australia
Date submitted for ethics approval [6] 5355 0
02/06/2008
Approval date [6] 5355 0
Ethics approval number [6] 5355 0
Ethics committee name [7] 5356 0
Peter MacCallum Cancer Institute
Ethics committee address [7] 5356 0
Ethics committee country [7] 5356 0
Australia
Date submitted for ethics approval [7] 5356 0
01/05/2008
Approval date [7] 5356 0
Ethics approval number [7] 5356 0
Ethics committee name [8] 5357 0
Royal Perth Hospital
Ethics committee address [8] 5357 0
Ethics committee country [8] 5357 0
Australia
Date submitted for ethics approval [8] 5357 0
02/06/2008
Approval date [8] 5357 0
Ethics approval number [8] 5357 0
Ethics committee name [9] 5358 0
St John of God Hospital, Subiaco
Ethics committee address [9] 5358 0
Ethics committee country [9] 5358 0
Australia
Date submitted for ethics approval [9] 5358 0
30/06/2008
Approval date [9] 5358 0
Ethics approval number [9] 5358 0
Ethics committee name [10] 5359 0
Royal Perth Hospital
Ethics committee address [10] 5359 0
Ethics committee country [10] 5359 0
Australia
Date submitted for ethics approval [10] 5359 0
02/06/2008
Approval date [10] 5359 0
Ethics approval number [10] 5359 0
Ethics committee name [11] 5360 0
Christchurch Hospital
Ethics committee address [11] 5360 0
Ethics committee country [11] 5360 0
New Zealand
Date submitted for ethics approval [11] 5360 0
05/08/2008
Approval date [11] 5360 0
Ethics approval number [11] 5360 0
Ethics committee name [12] 5361 0
Waikato Hospital
Ethics committee address [12] 5361 0
Ethics committee country [12] 5361 0
New Zealand
Date submitted for ethics approval [12] 5361 0
05/08/2008
Approval date [12] 5361 0
Ethics approval number [12] 5361 0

Summary
Brief summary
This study aims to determine whether intermittent treatment with the drug letrozole is more effective than continuous letrozole treatment in preventing the return of cancer in postmenopausal women with endocrine responsive breast cancer who have undergone 4 to 6 years of prior endocrine therapy.

Who is it for?
You may be eligible join this study if you are a postmenopausal woman who has had operable, non-inflammatory breast cancer but are now clinically disease-free. You must have completed 4 to 6 years of prior endocrine therapy with selective estrogen receptor modulators (SERM(s)), aromatase inhibitors (AI(s)), or a combination of both.

Trial details
Participants in this trial will be randomly (by chance) allocated to one of two groups. One group will take one 2.5mg letrozole tablet per day for 5 years. Participants in the other group will take letrozole 2.5mg tablets intermittently, i.e. once daily for the first 9 months of years 1 through 4, followed by 12 months in year 5.

Participants will be regularly assessed over the duration of the trial to determine whether continuous or intermittent letrozole treatment is more effective in preventing the return of cancer and prolonging survival.
Trial website
www.breastcancertrials.org.au
Trial related presentations / publications
Badger HD, Hunter LM, Chirgwin J, Forbes JF, Lindsay DF, Laycock I, Dempsey A. Strategies for Participant Recruitment: The SOLE Initiative. COSA 2010; Poster 222.

Forbes JF, Boyle F, Wilcken N, Lindsay DF, Leong E. Clinical Trials Open for Participant Entry. COSA 2010; Poster 242.

Colleoni M for the SOLE Collaborative and International Breast Cancer Study Groups. The SOLE Trial: International Breast Cancer Study Group (IBCSG 35-07) and Breast International Group (BIG 1-07) Study of Letrozole Extension. SABCS 2011;Poster OT2-02-01.

Colleoni M, Luo W, Karlsson P, Chirgwin JH, Aebi SP, Jerusalem GHM, Neven P, Hitre E, Graas M-P, Simoncini E, Kamby C, Thompson AM, Loibl S, Gavila J, Kuroi K, Gnant M, Rabaglio-Poretti, Regan MM, Coates AS, Goldhirsch A. SOLE (Study of Letrozole Extension): A phase III randomized clinical trial of continuous vs intermittent letrozole in postmenopausal women who have received 4-6 years of adjuvant endocrine therapy for lymph node-positive, early breast cancer (BC). Journal of Clinical Oncology 2017; 35, (suppl; abstr 503) [oral abstract][ASCO].
Public notes
Breast Cancer Trials formerly known as the Australia & New Zealand Breast Cancer Trials Group.

Contacts
Principal investigator
Name 28550 0
A/Prof Jacquie Chirgwin
Address 28550 0
Maroondah Breast Clinic
Maroondah Hospital
20 Grey Street
RINGWOOD EAST VIC 3135
Country 28550 0
Australia
Phone 28550 0
+61 (03) 9871-3582
Fax 28550 0
Email 28550 0
corinna.beckmore@bctrials.org.au
Contact person for public queries
Name 11707 0
Ms Corinna Beckmore
Address 11707 0
BCT
PO Box 283
The Junction NSW 2291
Country 11707 0
Australia
Phone 11707 0
+61 2 4925 5235
Fax 11707 0
+61 2 4925 3068
Email 11707 0
corinna.beckmore@bctrials.org.au
Contact person for scientific queries
Name 2635 0
A/Prof Jacquie Chirgwin
Address 2635 0
Maroondah Breast Clinic
Maroondah Hospital
20 Grey Street
RINGWOOD EAST VIC 3135
Country 2635 0
Australia
Phone 2635 0
+61 (03) 9871-3582
Fax 2635 0
Email 2635 0
corinna.beckmore@bctrials.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Journal publication details
Publication date and citation/details [1] 1066 0
Colleoni M, Luo W, Karlsson P, Chirgwin J, Aebi S, Jerusalem G, Neven P, Hitre E, Graas MP, Simoncini E, Kamby C, Thompson A, Loibl S, Gavilá J, Kuroi K, Marth C, Müller B, O'Reilly S, Di Lauro V, Gombos A, Ruhstaller T, Burstein H, Ribi K, Bernhard J, Viale G, Maibach R, Rabaglio-Poretti M, Gelber RD, Coates AS, Di Leo A, Regan MM, Goldhirsch A; SOLE Investigators. Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncology. 2018. 19(1):127-138. doi: 10.1016/S1470-2045(17)30715-5.
Attachments [1] 1066 0
Other publications
Have study results been made publicly available in another format?
Yes
Other publication details
Citation type [1] 1067 0
Presentation
Citation/DOI/link/details [1] 1067 0
Colleoni M, Luo W, Karlsson P, Chirgwin JH, Aebi SP, Jerusalem GHM, Neven P, Hitre E, Graas M-P, Simoncini E, Kamby C, Thompson AM, Loibl S, Gavila J, Kuroi K, Gnant M, Rabaglio-Poretti, Regan MM, Coates AS, Goldhirsch A. SOLE (Study of Letrozole Extension): A phase III randomized clinical trial of continuous vs intermittent letrozole in postmenopausal women who have received 4-6 years of adjuvant endocrine therapy for lymph node-positive, early breast cancer (BC). Journal of Clinical Oncology 2017; 35, (suppl; abstr 503) [oral abstract][ASCO].
Results – basic reporting
Results – plain English summary