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Trial registered on ANZCTR


Registration number
ACTRN12609000532202
Ethics application status
Approved
Date submitted
16/06/2009
Date registered
2/07/2009
Date last updated
29/01/2020
Date data sharing statement initially provided
14/01/2019
Date results information initially provided
14/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Tamoxifen and Exemestane Trial Bone Substudy - A substudy to Amendment 2 of the IBCSG 25-02 / BIG 3-02: Tamoxifen and Exemestane Trial (ACTRN12605000418673) hereby referred to as TEXT-2, which evaluates the effects of exemestane plus Gonadotropin-releasing hormone (GnRH) analogue as adjuvant therapy for premenopausal women with endocrine responsive breast cancer
Scientific title
IBCSG 25-02 / BIG 3-02: Tamoxifen and Exemestane Trial (TEXT) - A phase III trial evaluating the role of exemestane plus Gonadotropin-releasing hormone (GnRH)analogue as adjuvant therapy for premenopausal women with endocrine responsive breast cancer.

The TEXT-Bone Substudy evaluates serial bone markers for bone remodelling, serial growth factors, and bone mineral density for patients randomized to TEXT-2.
Secondary ID [1] 273540 0
IBCSG 25-02/BIG 3-02 TEXT-Bone
Universal Trial Number (UTN)
Trial acronym
TEXT-Bone
Linked study record
ACTRN12605000418673

Health condition
Health condition(s) or problem(s) studied:
Effects of adjuvant endocrine therapies on bone mineral density in pre-menopausal breast cancer patients. 236967 0
Condition category
Condition code
Cancer 237314 237314 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Prior to registration in the TEXT-Bone Substudy, patients must be randomised to the TEXT-2 parent trial (Protocol Amendment 2 of IBCSG 25-02 / BIG 3-02 Tamoxifen and Exemestane Trial - TEXT). TEXT-2 re-starts recruitment.

The TEXT trial will evaluate the worth of ovarian function suppression (achieved by long-term use of Gonadotropin-releasing hormone (GnRH) analogue (Triptorelin) 3.75mg by intramuscular injection every 28 days for 5 years from randomisation) plus exemestane 25mg orally daily until 5 years from date of randomisation (Exemestane should start after adjuvant chemotherapy has been completed or approximately six to eight weeks after the initiation of Gonadotropin-releasing hormone (GnRH) analogue (Triptorelin) whichever is later) compared with Gonadotropin-releasing hormone (GnRH) analogue (Triptorelin) 3.75mg by intramuscular injection every 28 days for 5 years from randomisation plus tamoxifen 20mg orally daily until 5 years from date of randomisation (Tamoxifen should start after adjuvant chemotherapy has been completed or approximatley six weeks to eight weeks after the initiation of Gonadotropin-releasing hormone (GnRH) analogue (Triptorelin), whichever is later) for premenopausal women with steroid hormone receptor positive early invasive breast cancer. Patients may either receive no chemotherapy or commence chemotherapy at the same time that Gonadotropin-releasing hormone (GnRH)analogue is initiated.

Women will be randomised in a 2-arm design to receive one of the following:

a. Ovarian Function Suppression (triptorelin) + Tamoxifen
b. Ovarian Function Suppression (triptorelin) + Exemestane


All treatment will be for 5 years.
Intervention code [1] 236739 0
Other interventions
Comparator / control treatment
Arm A - Tamoxifen as the control treatment: 20mg given orally daily until 5yrs from date of randomisation, unless relapse or intolerance should occur earlier. Triptorelin 3.75mg given by intramuscular injection every 28 days for 5 years from randomisation, unless relapse or intolerance should occur earlier or surgical oophorectomy or ovarian irradiation is subsequently performed.
Control group
Active

Outcomes
Primary outcome [1] 238129 0
Evaluate changes in bone mineral density (BMD) among pre-menopausal women randomized to TEXT-2 to receive either: A) triptorelin (GnRH analogue) for 5 years plus tamoxifen for 5 years; or B) triptorelin (GnRH analogue) for 5 years plus the steroidal aromatase inhibitor exemestane for 5 years.
Timepoint [1] 238129 0
Bone Mineral Density (BMD) measured by Dual energy X-ray absorptiometry (DEXA) in L1-L4 (postero-anterior, PA) region of the spine and hip is required as baseline, 12, 36, 60, and 72 month visits.
Secondary outcome [1] 242336 0
Evaluate serial serum markers for bone remodelling (C-telopeptide, osteocalcin, bone-specific alkaline phosphatase) and investigate their correlation with BMD.
Timepoint [1] 242336 0
Morning fasting blood samples for serum are required as baseline, 12, 36, 60, and 72 month visits.
Secondary outcome [2] 242356 0
Evaluate serial serum growth factors Insulin-like growth factor (IGF-1) and Insulin-like growth factor binding protein-3 (IGFBP-3) and investigate whether their time course correlates with bone mineral density (BMD).
Timepoint [2] 242356 0
Morning fasting blood samples for serum are required as baseline, 12, 36, 60, and 72 month visits.
Secondary outcome [3] 242357 0
Explore the role of serum Insulin-like growth factor (IGF-1) and Insulin-like growth factor binding protein-3 (IGFBP-3) FBP-3 as biomarkers of disease outcome (disease-free survival).
Timepoint [3] 242357 0
Morning fasting blood samples for serum are required as baseline, 12, 36, 60, and 72 month visits.

Eligibility
Key inclusion criteria
Patients must be eligible and enrolled in the TEXT-2 trial prior to enrollment in TEXT-Bone. Patients must have given informed consent for the TEXT-Bone substudy. the informed consent form must be signed and dated by the patient and her clinician.
Minimum age
No limit
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who have received bisphosphonate therapy (or other bone therapies such as Parathyroid hormone (PTH) or Strontium) within the previous 6 months or who are currently receiving therapy. Concomitant calcium and Vitamin D supplements are permitted and strongly recommended.
Patients who in the previous 6 months have had a bone fracture which in the investigator's judgement could be related to bone fragility.
Patients who have used a glucocorticoid (>5mg prednidone or equivalent) for more than one month in the previous 6 months.
Patients taking anticonvulsants within the previous 12 months.
Patients with clinical or biochemical malabsorption syndrome, or known vitamin D deficiency, active hyper- or hypoparathyroidism, or Paget's disease.
Uncontrolled thyroid disease, Cushing's disease or other pituitary diseases.
Any other bone disease (including osteomalacia, osteogenesis imperfecta).
Patients for whom serial BMD measuerment within the same institution is ompossible.

Study design
Purpose of the study
Educational / counselling / training
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The Statistical Centre at the National Health and Medical Research Council (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
Patients will be randomised to the parent TEXT-2 trial via computer generated stratified blocks. TEXT-2 patients opting to participate in the TEXT-Bone substudy will then be registered to participate in the trial.
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
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,QLD,SA,TAS,WA,VIC
Recruitment postcode(s) [1] 1792 0
2298
Recruitment postcode(s) [2] 1793 0
2170
Recruitment postcode(s) [3] 1794 0
2560
Recruitment postcode(s) [4] 1795 0
3135
Recruitment postcode(s) [5] 1796 0
3081
Recruitment postcode(s) [6] 1797 0
8006
Recruitment postcode(s) [7] 1798 0
4029
Recruitment outside Australia
Country [1] 8700 0
New Zealand
State/province [1] 8700 0

Funding & Sponsors
Funding source category [1] 237142 0
Other Collaborative groups
Name [1] 237142 0
Breast Cancer Trials
Address [1] 237142 0
PO Box 283
The Junction NSW 2291
Country [1] 237142 0
Australia
Funding source category [2] 237245 0
Other Collaborative groups
Name [2] 237245 0
International Breast Cancer Study Group (IBCSG)
Address [2] 237245 0
International Breast Cancer Study Group (IBCSG) Coordinating Centre
Effingerstrasse 40 CH-3008 BERN
Country [2] 237245 0
Switzerland
Primary sponsor type
Other Collaborative groups
Name
Breast Cancer Trials
Address
PO Box 283
The Junction NSW 2291
Country
Australia
Secondary sponsor category [1] 4631 0
Other Collaborative groups
Name [1] 4631 0
International Breast Cancer Study Group
Address [1] 4631 0
International Breast Cancer Study Group (IBCSG) Coordinating Centre
Effingerstrasse 40 CH-3008 BERN
Country [1] 4631 0
Switzerland

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 239252 0
Royal Brisbane and Women's Hospital
Ethics committee address [1] 239252 0
The Royal Brisbane & Women's Hospital Human Research Ethics Committee
Butterfield Street
HERSTON QLD 4029
Ethics committee country [1] 239252 0
Australia
Date submitted for ethics approval [1] 239252 0
Approval date [1] 239252 0
18/05/2009
Ethics approval number [1] 239252 0
2004/098

Summary
Brief summary
The purpose of this research is to compare the effect of the treatments (Tamoxifen and Exemestane) used in the main trial (TEXT-2) on bones. This will provide researchers and doctors with information as to whether these drugs are safe in terms of bone health and if there are increased or decreased risks of osteoporosis with the treatments.

Approximately 200 patient's will be enrolled in this sub-study worldwide. Every patient will be in the sub-study for an average period of six years. However, participation in the study could be shorter depending on the response to the treatment on the main study.
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 29726 0
A/Prof Prue Francis
Address 29726 0
Medical Oncology Department
Peter MacCallum Cancer Centre
Locked Bag 1
A'Beckett Street
MELBOURNE VIC 8006
Country 29726 0
Australia
Phone 29726 0
+61 (03) 8559-7902
Fax 29726 0
Email 29726 0
Prue.Francis@petermac.org
Contact person for public queries
Name 12973 0
Ms Corinna Beckmore
Address 12973 0
BCT
PO Box 283
The Junction NSW 2291
Country 12973 0
Australia
Phone 12973 0
+61 2 4925 5235
Fax 12973 0
+61 2 4925 3068
Email 12973 0
corinna.beckmore@bctrials.org.au
Contact person for scientific queries
Name 3901 0
A/Prof Prue Francis
Address 3901 0
Medical Oncology Department
Peter MacCallum Cancer Centre
Locked Bag 1
A'Beckett Street
MELBOURNE VIC 8006
Country 3901 0
Australia
Phone 3901 0
+61 (03) 8559-7902
Fax 3901 0
Email 3901 0
Prue.Francis@petermac.org

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The study is sponsored internationally by IBCSG and will be subject to their IPD sharing process.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary