ANZCTR - Registration

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12607000137493

Ethics application status

Approved

Date submitted

29/01/2007

Date registered

21/02/2007

Date last updated

17/09/2023

Date data sharing statement initially provided

20/02/2023

Date results information initially provided

20/02/2023

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]

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

Condition category

Condition code

Cancer

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]

Treatment: Drugs

Comparator / control treatment

Usual care

Control group

Active

Outcomes

Primary outcome [1]

New breast cancer events (in local, regional or distant sites, new breast cancer in the contralateral breast)

Timepoint [1]

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]

All cause mortality (death from any cause)

Timepoint [2]

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]

• Cause specific mortality

Timepoint [1]

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]

• Side effects of therapy

Timepoint [2]

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

Sex

Females

Can healthy volunteers participate?

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

1/03/2007

Actual

16/05/2007

Date of last participant enrolment

Anticipated

Actual

14/03/2012

Date of last data collection

Anticipated

Actual

28/10/2015

Sample size

Target

1700

Accrual to date

Final

360

Recruitment in Australia

Recruitment state(s)

NSW,VIC,SA,WA,TAS

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

Novartis Pharmaceuticals Australia Pty Ltd

Address [1]

Novartis Pharmaceuticals Australia Pty Ltd
54 Waterloo Road
NORTH RYDE NSW 2113

Country [1]

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]

None

Name [1]

N/A

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Newcastle Mater Misericordiae Hospital (Hunter New England Human Research Ethics Committee)

Ethics committee address [1]

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

08/12/2006

Ethics approval number [1]

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

Prof John F Forbes

Address

ANZBCTG
PO Box 283
The Junction NSW 2291

Country

Australia

Phone

+61 2 4985 0113

Fax

[email protected]

Contact person for public queries

Name

Ms Corinna Beckmore

Address

ANZBCTG
PO Box 283
The Junction NSW 2291

Country

Australia

Phone

+61 2 4925 5235

Fax

[email protected]

Contact person for scientific queries

Name

Prof John F Forbes

Address

ANZBCTG
PO Box 283
The Junction NSW 2291

Country

Australia

Phone

+61 2 4925 3068

Fax

+ 61 2 4985 0141

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

Anonymised Individual Patient Data (IPD) collected during the trial. The specific IPD to be shared (e.g. all data, published data, data of primary outcomes) will be as per the submitted research proposal and as assessed as appropriate by BCT.

When will data be available (start and end dates)?

Data will be made available for request after publication of the main/final study results; no end date.

Note that there may be additional circumstances preventing BCT from sharing requested data as outlined in the BCT Data Sharing Guidelines.

Available to whom?

Researchers who submit a research proposal and BCT Data Request Application, which is assessed by BCT to have appropriate scientific value. Refer to the BCT Data Sharing Guidelines

Available for what types of analyses?

To achieve the aims in the approved proposal.

How or where can data be obtained?

Subject to approval by Breast Cancer Trials [email protected] (refer to BCT Data Sharing Guidelines).

What supporting documents are/will be available?

Doc. No.	Type	Link	Other Details	Attachment
18388	Other	https://researchdata.edu.au/health/view/2538183	BCT Data Sharing Guidelines	81831-(Uploaded-18-08-2023-12-42-36)-Study-related document.pdf
20366	Study protocol	https://doi.org/10.58080/at5z-y012
20367	Data dictionary	https://doi.org/10.58080/at5z-y012

Results publications and other study-related documents

Documents added manually

Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Study results article	Yes		Zdenkowski N, Forbes JF, Boyle FM, Kannourakis G, ... [More Details]	81831-(Uploaded-17-02-2023-10-05-02)-Journal results publication.pdf

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Observation versus late reintroduction of letrozole as adjuvant endocrine therapy for hormone receptorpositive breast cancer (ANZ0501 LATER): An open-label randomised, controlled trial.	2016	https://dx.doi.org/10.1093/annonc/mdw055

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically