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Trial registered on ANZCTR


Registration number
ACTRN12605000416695
Ethics application status
Approved
Date submitted
12/09/2005
Date registered
16/09/2005
Date last updated
6/07/2021
Date data sharing statement initially provided
14/01/2019
Date results information initially provided
14/01/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
IBCSG 24-02 / BIG 2-02: Suppression of Ovarian Function Trial
Scientific title
IBCSG 24-02 / BIG 2-02: Suppression of Ovarian Function Trial. A phase III trial evaluating the role of ovarian function suppression and the role of Exemestane as adjuvant therapies for premenopausal women with endocrine responsive breast cancer.
Secondary ID [1] 166 0
ClinicalTrials.gov: NCT00066690
Universal Trial Number (UTN)
Trial acronym
SOFT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Adjuvant Breast Cancer 525 0
Condition category
Condition code
Cancer 605 605 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
IBCSG 24-02 / BIG 2-02 (SOFT) is being conducted internationally by the International Breast Cancer Study Group (IBCSG). The study is coordinated in Australia and New Zealand by Breast Cancer Trials (formerly the Australia and New Zealand Breast Cancer Trials Group). This study will evaluate the worth of ovarian function suppression (achieved by long-term use of GnRH analogue (triptorelin), surgical oophorectomy or ovarian irradiation) plus tamoxifen compared with tamoxifen alone for premenopausal women with steroid hormone receptor positive early invasive breast cancer who either receive no adjuvant chemotherapy or remain premenopausal following adjuvant and/or neoadjuvant chemotherapy. In addition, the worth of exemestane will be evaluated for this premenopausal patient population by comparing ovarian function suppression plus exemestane with tamoxifen alone and by comparing ovarian function suppression plus exemestane with ovarian function suppression plus tamoxifen. IBCSG 24-02 / BIG 2-02 (SOFT) is an international, multicentre, randomised phase III clinical trial of 3000 premenopausal women who have had histologically or cytologically confirmed, receptor-positive primary breast cancer. Women will be randomised in a 3-arm design to receive one of the following: a. Tamoxifen b. Ovarian Function Suppression + tamoxifen c. Ovarian Function Suppression + exemestane Patients are stratified according to institution, prior chemotherapy, number of positive nodes and the intended initial method of ovarian function suppression if assigned by randomization. All treatment will be for 5 years.
Intervention code [1] 487 0
Treatment: Drugs
Comparator / control treatment
Tamoxifen 20mg, orally, daily for five years
Control group
Active

Outcomes
Primary outcome [1] 702 0
Disease-free survival
Timepoint [1] 702 0
Disease free survival will be assessed annually starting when 200 events have been observed in the three treatment arms for a total of 5 analyses over 6.9 years.
Secondary outcome [1] 1442 0
To compare overall survival.
Timepoint [1] 1442 0
Overall survival will be assessed every 3 months in Year 1, every 6 months during years 2-6 and yearly thereafter until death
Secondary outcome [2] 1443 0
Systemic disease-free survival
Timepoint [2] 1443 0
Systemic disease survival will be assessed every 3 months in Year 1, every 6 months during years 2-6 and yearly thereafter until death
Secondary outcome [3] 1444 0
Quality of life
Timepoint [3] 1444 0
Quality of Life will be assessed at baseline, and at months 6, 12, 18, 24, 36, 48, 60 and 72
Secondary outcome [4] 1445 0
Sites of first treatment failure
Timepoint [4] 1445 0
Sites of first treatment failure will be assessed every 3 months in Year 1, every 6 months during years 2-6 and yearly thereafter until death
Secondary outcome [5] 1446 0
Late side effects of early menopause
Timepoint [5] 1446 0
Late side effects of early menopause will be assessed every 3 months in Year 1, every 6 months during years 2-6 and yearly thereafter until death
Secondary outcome [6] 1447 0
Incidence of second (non-breast) malignancies
Timepoint [6] 1447 0
Incidence of second (non-breast) malignancies will be assessed every 3 months in Year 1, every 6 months during years 2-6 and yearly thereafter until time of onset or until death
Secondary outcome [7] 1448 0
Causes of death without cancer event between the treatment arms.
Timepoint [7] 1448 0
Causes of death without cancer event between the treatment arms will be assessed every 3 months in Year 1, every 6 months during years 2-6 and yearly thereafter intil time of onset or until death

Eligibility
Key inclusion criteria
Pre-menopausal women with histologically proven, hormone receptor positive, completely resected breast cancer which is confined to the breast and axillary nodes without metastases; axillary node dissection or a negative axillary sentinel node biopsy; geographically accessible for follow up; written informed consent provided.
Minimum age
18 Years
Maximum age
Not stated
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Post-menopausal women; distant metastatic disease; locally advanced inoperable breast cancer; supraclavicular node involvement; enlarged internal mammary nodes; bilateral invasive breast cancer; positive final margins; clinically detectable residual axillary disease; history of prior ipsilateral or contralateral invasive breast cancer; previous or concomitant malignancy; other non-malignant systemic diseases that would prevent prolonged follow-up; bilateral oophorectomy or ovarian irradiation or are planning oophorectomy within 5 years of entry; pregnant or lactating at randomization; desire a pregnancy within 5 years or plan to use additional hormone therapy during next 5 years (including hormonal contraception); neoadjuvant or adjuvant endocrine therapy for more than 6 months after breast cancer diagnosis; tamoxifen or other SERM or HRT within 1 year prior to breast cancer diagnosis; patients who have received GnRH analogues as part of their breast cancer treatment prior to 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)
The ANZ BCTG Statistical Centre at the NHMRC Clinical Trials Centre, University of Sydney will provide a central randomisation service by fax for all Australian and New Zealand institutions. At the time of study entry all participants will be allocated a treatment code via a web-based randomization system and study drug will be supplied in accordance with the treatment code.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated stratified blocks.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
22/11/2004
Actual
17/03/2005
Date of last participant enrolment
Anticipated
Actual
18/02/2010
Date of last data collection
Anticipated
31/12/2023
Actual
Sample size
Target
3000
Accrual to date
Final
3066
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,WA,VIC
Recruitment outside Australia
Country [1] 8304 0
New Zealand
State/province [1] 8304 0

Funding & Sponsors
Funding source category [1] 661 0
Self funded/Unfunded
Name [1] 661 0
Breast Cancer Trials
Country [1] 661 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Breast Cancer Trials
Address
PO Box 283
The Junction NSW 2291
Country
Australia
Secondary sponsor category [1] 551 0
Other Collaborative groups
Name [1] 551 0
International Breast Cancer Study Group
Address [1] 551 0
IBCSG Coordinating Center
Effingerstrasse 40
3008 Bern
SWITZERLAND
Country [1] 551 0
Switzerland

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 1800 0
The Alfred Hospital
Ethics committee address [1] 1800 0
Ethics committee country [1] 1800 0
Australia
Date submitted for ethics approval [1] 1800 0
Approval date [1] 1800 0
Ethics approval number [1] 1800 0
Ethics committee name [2] 1801 0
Austin Health
Ethics committee address [2] 1801 0
Ethics committee country [2] 1801 0
Australia
Date submitted for ethics approval [2] 1801 0
Approval date [2] 1801 0
Ethics approval number [2] 1801 0
Ethics committee name [3] 1802 0
Ballarat Oncology and Haematology Services
Ethics committee address [3] 1802 0
Ethics committee country [3] 1802 0
Australia
Date submitted for ethics approval [3] 1802 0
Approval date [3] 1802 0
Ethics approval number [3] 1802 0
Ethics committee name [4] 1803 0
Box Hill Hospital
Ethics committee address [4] 1803 0
Ethics committee country [4] 1803 0
Australia
Date submitted for ethics approval [4] 1803 0
Approval date [4] 1803 0
Ethics approval number [4] 1803 0
Ethics committee name [5] 1804 0
Concord Hospital
Ethics committee address [5] 1804 0
Ethics committee country [5] 1804 0
Australia
Date submitted for ethics approval [5] 1804 0
Approval date [5] 1804 0
Ethics approval number [5] 1804 0
Ethics committee name [6] 1805 0
Frankston Hospital (Rosebud Hospital Satellite Site)
Ethics committee address [6] 1805 0
Ethics committee country [6] 1805 0
Australia
Date submitted for ethics approval [6] 1805 0
Approval date [6] 1805 0
Ethics approval number [6] 1805 0
Ethics committee name [7] 1806 0
Geelong Hospital
Ethics committee address [7] 1806 0
Ethics committee country [7] 1806 0
Australia
Date submitted for ethics approval [7] 1806 0
Approval date [7] 1806 0
Ethics approval number [7] 1806 0
Ethics committee name [8] 1807 0
Liverpool Hospital
Ethics committee address [8] 1807 0
Ethics committee country [8] 1807 0
Australia
Date submitted for ethics approval [8] 1807 0
Approval date [8] 1807 0
Ethics approval number [8] 1807 0
Ethics committee name [9] 1808 0
Macarthur Cancer Therapy Centre
Ethics committee address [9] 1808 0
Ethics committee country [9] 1808 0
Australia
Date submitted for ethics approval [9] 1808 0
Approval date [9] 1808 0
Ethics approval number [9] 1808 0
Ethics committee name [10] 1809 0
Maroondah Hospital
Ethics committee address [10] 1809 0
Ethics committee country [10] 1809 0
Australia
Date submitted for ethics approval [10] 1809 0
Approval date [10] 1809 0
Ethics approval number [10] 1809 0
Ethics committee name [11] 1810 0
Mater Hospital, Sydney
Ethics committee address [11] 1810 0
Ethics committee country [11] 1810 0
Australia
Date submitted for ethics approval [11] 1810 0
Approval date [11] 1810 0
Ethics approval number [11] 1810 0
Ethics committee name [12] 1811 0
St Vincents and Mercy Private
Ethics committee address [12] 1811 0
Ethics committee country [12] 1811 0
Australia
Date submitted for ethics approval [12] 1811 0
Approval date [12] 1811 0
Ethics approval number [12] 1811 0
Ethics committee name [13] 1812 0
Monash Medical Centre
Ethics committee address [13] 1812 0
Ethics committee country [13] 1812 0
Australia
Date submitted for ethics approval [13] 1812 0
Approval date [13] 1812 0
Ethics approval number [13] 1812 0
Ethics committee name [14] 1813 0
Mount Hospital
Ethics committee address [14] 1813 0
Ethics committee country [14] 1813 0
Australia
Date submitted for ethics approval [14] 1813 0
Approval date [14] 1813 0
Ethics approval number [14] 1813 0
Ethics committee name [15] 1814 0
Newcastle Mater Misericordiae Hospital
Ethics committee address [15] 1814 0
Ethics committee country [15] 1814 0
Australia
Date submitted for ethics approval [15] 1814 0
Approval date [15] 1814 0
Ethics approval number [15] 1814 0
Ethics committee name [16] 1815 0
Peter MacCallum Cancer Centre
Ethics committee address [16] 1815 0
Ethics committee country [16] 1815 0
Australia
Date submitted for ethics approval [16] 1815 0
Approval date [16] 1815 0
01/11/2004
Ethics approval number [16] 1815 0
Ethics committee name [17] 1816 0
Prince of Wales Hospital
Ethics committee address [17] 1816 0
Ethics committee country [17] 1816 0
Australia
Date submitted for ethics approval [17] 1816 0
Approval date [17] 1816 0
Ethics approval number [17] 1816 0
Ethics committee name [18] 1817 0
Riverina Cancer Care Centre
Ethics committee address [18] 1817 0
Ethics committee country [18] 1817 0
Australia
Date submitted for ethics approval [18] 1817 0
Approval date [18] 1817 0
Ethics approval number [18] 1817 0
Ethics committee name [19] 1818 0
Royal Adelaide Hospital
Ethics committee address [19] 1818 0
Ethics committee country [19] 1818 0
Australia
Date submitted for ethics approval [19] 1818 0
Approval date [19] 1818 0
Ethics approval number [19] 1818 0
Ethics committee name [20] 1819 0
Royal Brisbane and Womens Hospital
Ethics committee address [20] 1819 0
Ethics committee country [20] 1819 0
Australia
Date submitted for ethics approval [20] 1819 0
Approval date [20] 1819 0
Ethics approval number [20] 1819 0
Ethics committee name [21] 1820 0
Royal Hobart Hospital
Ethics committee address [21] 1820 0
Ethics committee country [21] 1820 0
Australia
Date submitted for ethics approval [21] 1820 0
Approval date [21] 1820 0
Ethics approval number [21] 1820 0
Ethics committee name [22] 1821 0
Royal North Shore Hospital
Ethics committee address [22] 1821 0
Ethics committee country [22] 1821 0
Australia
Date submitted for ethics approval [22] 1821 0
Approval date [22] 1821 0
Ethics approval number [22] 1821 0
Ethics committee name [23] 1822 0
Royal Prince Alfred Hospital
Ethics committee address [23] 1822 0
Ethics committee country [23] 1822 0
Australia
Date submitted for ethics approval [23] 1822 0
Approval date [23] 1822 0
Ethics approval number [23] 1822 0
Ethics committee name [24] 1823 0
St George Hospital
Ethics committee address [24] 1823 0
Ethics committee country [24] 1823 0
Australia
Date submitted for ethics approval [24] 1823 0
Approval date [24] 1823 0
Ethics approval number [24] 1823 0
Ethics committee name [25] 1824 0
St John of God, Bunbury
Ethics committee address [25] 1824 0
Ethics committee country [25] 1824 0
Australia
Date submitted for ethics approval [25] 1824 0
Approval date [25] 1824 0
Ethics approval number [25] 1824 0
Ethics committee name [26] 1825 0
St John of God, Subiaco
Ethics committee address [26] 1825 0
Ethics committee country [26] 1825 0
Australia
Date submitted for ethics approval [26] 1825 0
Approval date [26] 1825 0
Ethics approval number [26] 1825 0
Ethics committee name [27] 1826 0
St Vincents Hospital, Sydney
Ethics committee address [27] 1826 0
Ethics committee country [27] 1826 0
Australia
Date submitted for ethics approval [27] 1826 0
Approval date [27] 1826 0
Ethics approval number [27] 1826 0

Summary
Brief summary
Phase 3

This trial evaluates the role of suppressing ovarian function, and also the role of the drug exemestane as preventative therapies for premenopausal women with breast cancer that responds to hormones.

Who is it for?
You can join this study if you are a woman with early breast cancer that responds to hormones and you are still premenopausal even after treatment (with surgery or chemotherapy).

Trial details
Chemotherapy, hormone tablets, and turning off the ovaries all reduce the risk of breast cancer coming back in young women with early breast cancer that responds to hormone therapy. However it is unclear whether all 3 are necessary or what the best way to combine them is. This study will determine if turning off the ovaries for 5 years helps young women with early breast cancer

Participants will be randomly assigned to receive Tamoxifen alone (standard treatment for this group of patients), ovarian function suppression with Tamoxifen, or ovarian function suppression with Exemestane (a drug designed to reduce the amount of oestrogen in the body, so as to reduce cancer growth). Patients assigned to ovarian function suppression as part of their treatment will be able to choose the method of treatment (either by tablet, radiotherapy or surgery).
Trial website
www.breastcancertrials.org.au
Trial related presentations / publications
Public notes
Breast Cancer Trials formerly known as the Australia & New Zealand Breast Cancer Trials Group.

Contacts
Principal investigator
Name 35489 0
A/Prof Prue Francis
Address 35489 0
Medical Oncology Department
Peter MacCallum Cancer Centre
Locked Bag 1
A'Beckett Street
MELBOURNE VIC 8006
Country 35489 0
Australia
Phone 35489 0
+61 (03) 8559-7902
Fax 35489 0
Email 35489 0
Prue.Francis@petermac.org
Contact person for public queries
Name 9676 0
Ms Corinna Beckmore
Address 9676 0
BCT
PO Box 283
The Junction NSW 2291
Country 9676 0
Australia
Phone 9676 0
+61 2 4925 5235
Fax 9676 0
+61 4925 3068
Email 9676 0
corinna.beckmore@bctrials.org.au
Contact person for scientific queries
Name 604 0
A/Prof Prue Francis
Address 604 0
Medical Oncology Department
Peter MacCallum Cancer Centre
Locked Bag 1
A'Beckett Street
MELBOURNE VIC 8006
Country 604 0
Australia
Phone 604 0
+61 (03) 8559-7902
Fax 604 0
Email 604 0
Prue.Francis@petermac.org

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?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
Current Study Results
No documents have been uploaded by study researchers.

Update to Study Results
Documents added automatically
No additional documents have been identified.