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Trial registered on ANZCTR


Registration number
ACTRN12607000137493
Ethics application status
Approved
Date submitted
29/01/2007
Date registered
21/02/2007
Date last updated
11/11/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
ANZ 0501 / LATER adjuvant Aromotase inhibitor Therapy for postmenopausal women with Endocrine Responsive breast cancer (LATER)
Scientific title
Randomised trial of letrozole plus usual care versus usual care without letrozole to prevent new breast cancer events in postmenopausal women who have completed a minimum of 4 years of adjuvant endocrine therapy for early hormone responsive breast cancer more than 1 year previous and who are disease free at trial entry.
Secondary ID [1] 253232 0
ANZ 0501 LATER
Universal Trial Number (UTN)
Trial acronym
LATER
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Endocrine Responsive Breast Cancer 1630 0
Condition category
Condition code
Cancer 1738 1738 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients are randomised to the following arm: Letrozole 2.5mg orally daily for 5 years
Intervention code [1] 1576 0
Treatment: Drugs
Comparator / control treatment
Usual care
Control group
Active

Outcomes
Primary outcome [1] 2418 0
New breast cancer events (in local, regional or distant sites, new breast cancer in the contralateral breast)
Timepoint [1] 2418 0
Patients are assessed by the clinician for new breast cancer events and survival status 6 monthly in the first year and annually thereafter until year 10 on study.
Primary outcome [2] 2419 0
All cause mortality (death from any cause)
Timepoint [2] 2419 0
Patients are assessed by the clinician for new breast cancer events and survival status 6 monthly in the first year and annually thereafter until year 10 on study.
Secondary outcome [1] 4191 0
• Cause specific mortality
Timepoint [1] 4191 0
Patients are assessed by the clinician for survival status 6 monthly in the first year and annually thereafter until year 10 on study.
Secondary outcome [2] 4192 0
• Side effects of therapy
Timepoint [2] 4192 0
Patients are assessed by the clinician for survival status 6 monthly in the first year and annually thereafter until year 10 on study. Side effects of therapy will be documented at one month on study via phone follow-up with the patient. The clinician will also assess the patient for side effects 6 monthly in the first year and annually thereafter until year 10 on study.

Eligibility
Key inclusion criteria
Patients must be postmenopausal, which is defined as meeting one or more of the
following criteria:
prior bilateral oophorectomy aged 60 years or more; if the patient has any clinical evidence of ovarian
function, FSH levels must be assessed and be in the postmenopausal range.
aged under 60 years:
a) with a uterus and amenorrhoea for at least 12 months prior to trial
entry (see Note 2)
b) with amenorrhoea for less than 12 months prior to trial entry and an
follicle stimulating hormone (FSH) level in the postmenopausal range
c) without a uterus and an FSH level in the postmenopausal range
Note 1: Patients who have taken hormone replacement therapy (HRT) must have ceased HRT at least 8 weeks prior to
randomisation and be free of per vagina bleeding for this time. FSH levels must be assessed
after the completion of this 8 week interval.
Note 2: Women aged under 60 years who have developed amenorrhoea after undergoing
endometrial ablation or been rendered amenorrhoeic by adjuvant chemotherapy are not eligible
unless FSH is in the postmenopausal range.
Patients must have had previous completely resected hormone responsive (oestrogen receptor (ER) and/or
Progesterone receptor (PgR) positive) invasive breast cancer determined by immunohistochemistry.
Patients must have completed a minimum of 4 years of adjuvant endocrine therapy
(Selective oestrogen receptor modulator (SERM) / Aromatase Inhibitor (AI) / Other - including ovarian function suppression, combination or sequential
Adjuvant endocrine therapy (AET), blinded trial AET) at least 12 months previously. It is anticipated that women who have completed AET much longer than 1 year ago will be entered onto the trial; the only limiting factor being that women are in good health and suitable for prolonged follow-up.
Patients who have had bilateral breast cancer are eligible provided that they have had at
least one hormone responsive tumour. All treatment for hormone non-responsive
tumours must have been completed and these tumours must have been diagnosed at
least 5 years ago.
Currently free of breast cancer.
Adequate bone marrow function, renal function and hepatic function within 6 months
prior to randomisation. Additional investigations including chest x-ray, computed tomography scan (CT), magnetic imaging scan (MRI) or positron emission tomograpy (PET)
scan should be carried out as medically indicated to rule out metastatic disease.
Bilateral mammogram performed within 12 months prior to randomisation unless the
initial surgery was a total mastectomy in which case a unilateral mammogram may be
performed. A mammogram is not required if the patient has had a bilateral mastectomy.
Bone health must be evaluated prior to randomisation and be deemed clinically as
adequate. A Bone Mineral Density Scan (DXA Scan) of hip, femoral neck, or lumbar
spine must be performed within 12 months prior to randomisation and the T-score must be greater than or equal to minus 4.0. (Note: Spinal x-rays to assess for low trauma vertebral fractures are also
strongly recommended).
Note: If a woman with osteoporosis (T-score between minus 2.5 and minus 4.0) and/or with low trauma
vertebral fractures wishes to join the trial she must receive appropriate care for osteoporosis
under the direction of her general practitioner or treating clinician.
Must be geographically accessible for follow-up.
Life expectancy of at least 10 years.
Ability to fully understand, sign and date the written informed consent document, and
agree to the collection and use of breast cancer tumour specimens where available as
specified in the protocol and Participant Information Sheet and Consent Form.
Minimum age
45 Years
Maximum age
Not stated
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Premenopausal patients.
Patients previously diagnosed with only hormone non-responsive early breast cancer.
Patients with any local recurrence or distant metastases of breast cancer. Any
suspicious manifestation requires appropriate investigation to exclude metastases.
Patients with non-malignant systemic diseases which would prevent prolonged followup,
or in the opinion of the investigator, would place the woman at unusual risk or
confound assessment for breast cancer events and the results of the trial.
Any previous non-breast cancer within the last 5 years, except adequately treated nonmelanoma
skin cancer, curatively treated in situ cancer of the cervix, or other solid
tumours curatively treated more than 5 years ago with no evidence of recurrence.
Intention to continue or commence systemic oestrogen and/or progesterone based
Hormone Replacement Therapy (HRT).
Osteoporotic with a T-score less than or equal to minus 4.0 within 12 months prior to randomisation.
Patients with diagnosed hypercholesterolaemia, unless currently being treated with
cholesterol lowering drugs and/or therapeutic lifestyle changes under the care of their
medical practitioner.
History of allergic reactions attributed to compounds of similar chemical or biologic
composition to Letrozole.
Any co-existing medical or psychiatric condition that would limit compliance with trial
requirements.
Treatment with non-approved or experimental drug on a different clinical trial during the
three months before randomisation.
Prior treatment on a designated trial for breast cancer if permission has not been
obtained from the sponsors of the original trial for the patient to participate in LATER.

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 fax
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Minimisation. Before randomisation, patients will be stratified according to institution, nodal status, type of prior adjuvant endocrine therapy.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Delete this as there are no other design features.
Phase
Phase 3
Type of endpoint(s)
Safety/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,SA,WA,TAS

Funding & Sponsors
Funding source category [1] 1888 0
Self funded/Unfunded
Name [1] 1888 0
Novartis Pharmaceuticals Australia Pty Ltd
Address [1] 1888 0
Novartis Pharmaceuticals Australia Pty Ltd
54 Waterloo Road
NORTH RYDE NSW 2113
Country [1] 1888 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australia and New Zealand Breast Cancer Trials Group
Address
PO Box 155
Hunter Region Mail Centre NSW 2310
Country
Australia
Secondary sponsor category [1] 1707 0
None
Name [1] 1707 0
N/A
Address [1] 1707 0
Country [1] 1707 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 3513 0
Newcastle Mater Misericordiae Hospital (Hunter New England Human Research Ethics Committee)
Ethics committee address [1] 3513 0
Ethics committee country [1] 3513 0
Australia
Date submitted for ethics approval [1] 3513 0
Approval date [1] 3513 0
08/12/2006
Ethics approval number [1] 3513 0
06/11/22/3.03

Summary
Brief summary
The major concern for women on long term follow up after breast cancer has been treated, is fear of the reoccurrence of disease. This study will test a new strategy to prevent disease reocurrence and death due to breast cancer. The purpose of the study is to find out whether later re-treatment of participants with adjuvant letrozole therapy can prevent or delay new breast cancers from reoccurring in postmenopausal women previously treated with adjuvant endocrine therapy
Trial website
www.anzbctg.org
Trial related presentations / publications
N/A
Public notes

Contacts
Principal investigator
Name 27510 0
Prof John F Forbes
Address 27510 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 27510 0
Australia
Phone 27510 0
+61 2 4985 0113
Fax 27510 0
Email 27510 0
enquiries@anzbctg.org
Contact person for public queries
Name 10765 0
Ms Corinna Beckmore
Address 10765 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 10765 0
Australia
Phone 10765 0
+61 2 4925 5235
Fax 10765 0
Email 10765 0
enquiries@anzbctg.org
Contact person for scientific queries
Name 1693 0
Prof John F Forbes
Address 1693 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 1693 0
Australia
Phone 1693 0
+61 2 4925 3068
Fax 1693 0
+ 61 2 4985 0141
Email 1693 0
enquiries@anzbctg.org

No information has been provided regarding IPD availability
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