UMIN-CTR Clinical Trial

Basic information
Public title	Phase III trial evaluating the role of continuous letrozole versus intermittent letrozole following 4 to 6 years of prior adjuvant endocrine therapy for postmenopausal women with hormone-receptor positive, node positive early stage breast cancer
Acronym	JBCRG(SOLE study)
Scientific Title	Phase III trial evaluating the role of continuous letrozole versus intermittent letrozole following 4 to 6 years of prior adjuvant endocrine therapy for postmenopausal women with hormone-receptor positive, node positive early stage breast cancer
Scientific Title:Acronym	JBCRG(SOLE study)
Region	Japan Asia(except Japan) North America South America Australia Europe Africa

Condition
Condition	Postmenopausal patients with breast cancer
Classification by specialty	Breast surgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To compare continuous letrozole for five years with intermittent letrozole over a five year period for postmenopausal women who are disease-free following 4-6 years of prior adjuvant endocrine therapy with SERM(s) and/or AI(s) for endocrine-responsive, node-positive, operable breast cancer.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Explanatory
Developmental phase	Phase III

Assessment
Primary outcomes	Disease-free survival (DFS): time from randomization 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.
Key secondary outcomes	Overall survival (OS), distant disease-free survival (DDFS), breast cancer free interval (BCFI), sites of first failure, second (non-breast) malignancies, deaths without prior cancer events, and adverse events.

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification	YES
Dynamic allocation	YES
Institution consideration
Blocking
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	A: Continuous letrozole 2.5 mg daily for 5 years
Interventions/Control_2	B: Intermittent letrozole 2.5 mg daily for the first 9 months of years 1 through 4, followed by 12 months in year 5
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	Not applicable
Age-upper limit	Not applicable
Gender	Female
Key inclusion criteria	1. Completely resected, non-inflammatory breast cancer 2. ER and/or PgR positive 3. postmenopausal 4. Axillary and/or internal mammary lymph nodes positive 5. Any (neo-)adjuvant treatment 6. 4 to 6 years of SERM or AI treatment Last dose of SERM/AI within 1 year prior to randomization 7. No evidence of recurrence at any time 8. No bilateral breast cancer 9. No bone fracture due to osteoporosis during SERM/AI treatment 10. Pathology material from primary tumor available 11. No previous or concomitant malignancy 12. Signed informed consent
Key exclusion criteria	1. Patients must have clinically adequate hepatic function. 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.
Target sample size	4800

Research contact person
Name of lead principal investigator	1st name Marco Middle name Last name Colleoni
Organization	IBCSG/European Institute of Oncology
Division name	Division of Medical Onclogy
Zip code	20141
Address	Via Ripamonti 435 20141 Milan,Italy
TEL	+39-2-5748-9439
Email	marco.colleoni@ieo.it

Public contact
Name of contact person	1st name Jun Middle name Last name Fukase
Organization	Japan Breast Cancer Research Group (JBCRG)
Division name	Administrative office
Zip code	103-0016
Address	9-4-3F, Nihonbashikoamicho, Chuo-ku, Tokyo 103-0016, Japan
TEL	+81-3-6264-8873
Homepage URL	http://www.jbcrg.jp/
Email	office@jbcrg.jp

Sponsor
Institute	International Breast Cancer Study Group
Institute
Department

Funding Source
Organization	International Breast Cancer Study Group IBCSG
Organization
Division
Category of Funding Organization	Outside Japan
Nationality of Funding Organization	Switzerland

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	International Breast Cancer Study Group IBCSG
Address	Effingerstrasse 40, 3008 Bern, Switzerland
Tel	+41 31 511 94 00
Email	ibcsgcc@ibcsg.org

Secondary IDs
Secondary IDs	YES
Study ID_1	NCT00553410
Org. issuing International ID_1	Clinical Trials.gov
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	熊本大学病院（熊本県）、都立駒込病院（東京都）、八尾市立病院（大阪府）、新潟県立がんセンター（新潟県）、大阪医療センター（大阪府）、広島大学病院（広島県）、四国がんセンター（愛媛県）、相原病院（大阪府）、北海道がんセンター（北海道）、筑波大学附属病院（茨城県）、九州がんセンター（福岡県）、相良病院（鹿児島県）、京都大学（京都府）、愛知県がんセンター（愛知県）、自治医科大学附属病院（栃木県）

Other administrative information
Date of disclosure of the study information	2010 Year 11 Month 01 Day

Related information
URL releasing protocol	https://clinicaltrials.gov/ProvidedDocs/10/NCT00553410/Prot_000.pdf
Publication of results	Published

Result
URL related to results and publications	http://dx.doi.org/10.1016/S1470-2045(17)30715-5
Number of participants that the trial has enrolled	4884
Results	From the current analysis, we conclude that extended treatment with intermittent letrozole did not improve disease-free survival versus treatment with continuous letrozole. The safety, quality-of-life, and efficacy results of the intermittent administration provide clinically relevant information about extended adjuvant endocrine therapy with letrozole and support the safety of this option for temporary treatment breaks in selected patients who might require them.
Results date posted	2021 Year 08 Month 24 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results	2017 Year 11 Month 17 Day
Baseline Characteristics	- Female - Must be postmenopausal by any of the following criteria: -Patients of any age who have had a bilateral oophorectomy (including radiation castration AND amenorrheic for > 3 months) - Patients 56 years old or older with any evidence of ovarian function must have biochemical evidence of definite postmenopausal status (defined as estradiol, luteinizing hormone [LH], and follicle-stimulating hormone [FSH] in the postmenopausal range) - Patients 55 years old or younger must have biochemical evidence of definite postmenopausal status (defined as estradiol, LH, and FSH in the postmenopausal range) - Patients who have received prior luteinizing-hormone releasing-hormone (LHRH) analogues within the last year are eligible if they have definite evidence of postmenopausal status as defined above - Clinically adequate hepatic function - No bone fracture due to osteoporosis at any time during the 4-6 years of prior therapy - No prior or current malignancy except adequately treated basal cell or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, or contra- or ipsilateral in situ breast carcinoma - No other nonmalignant systemic diseases (cardiovascular, renal, lung, etc.) that would prevent prolonged follow-up - No psychiatric, addictive, or any other disorder that compromises compliance with protocol requirements
Participant flow	- See Disease Characteristics - More than 12 months since prior and no other concurrent endocrine SERM/AI therapy - Any type of prior adjuvant therapy allowed including, but not limited to, any of the following: -Neoadjuvant chemotherapy -Neoadjuvant endocrine therapy -Adjuvant chemotherapy -Trastuzumab (Herceptin) -Ovarian ablation -Gonadotropin releasing hormone analogues -Lapatinib ditosylate -No concurrent hormone-replacement therapy, bisphosphonates (except for treatment of bone loss), or any other investigational agent
Adverse events	Please refer NCT00553410
Outcome measures	Primary: Disease-free Survival (DFS) Secondary: Overall Survival, Distant Recurrence-free Interval (DRFI), Breast Cancer-free Interval
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2007 Year 08 Month 01 Day
Date of IRB	2007 Year 08 Month 01 Day
Anticipated trial start date	2007 Year 08 Month 01 Day
Last follow-up date	2018 Year 12 Month 31 Day
Date of closure to data entry	2019 Year 02 Month 28 Day
Date trial data considered complete	2019 Year 03 Month 01 Day
Date analysis concluded	2019 Year 05 Month 01 Day

Other
Other related information

Management information
Registered date	2010 Year 10 Month 27 Day
Last modified on	2021 Year 11 Month 11 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000005337