Hormone Sensitive Resected Primary Breast Cancer in Postmenopausal WomenPhase 3NCT00171704

A Study to Evaluate the Effect of Letrozole and Tamoxifen on Bone and Lipids in Postmenopausal Women With Breast Cancer

A Phase 3 study testing Letrozole and Tamoxifen in people with Hormone Sensitive Resected Primary Breast Cancer in Postmenopausal Women, run by Novartis Pharmaceuticals at 13 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Estrogen is known to be a regulator of bone and lipid metabolism. Letrozole is a potent inhibitor of estrogen synthesis. This study evaluated the effects of letrozole and tamoxifen on bone and lipid metabolism in postmenopausal women with resected, receptor positive early breast cancer. Read more about this study

Who is it for?: Ages 50 years and older, women only
Conditions the study is for: Hormone Sensitive Resected Primary Breast Cancer in Postmenopausal Women
What is being tested?: Letrozole and Tamoxifen
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 263 participants
Where: 13 sitesin 2 countries
Study dates: Apr 2005to Mar 2011
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 50 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

Female
Post-menopausal hormone status defined as:
Patients with menostasis (amenorrhea) > 12 months or history of oophorectomy.
Patients ≥ 55 years with history of hysterectomy or having continued/renewed menstruation on cyclic hormone treatment.
Patients of 50-54 years: Menopausal status was determined on the basis of follicle-stimulating hormone (FSH)/luteinizing hormone (LH) values.
Histologically confirmed resected breast cancer and eligible for adjuvant endocrine therapy. As a minimum, patients had to have receptor-positive tumors, which were defined either as estrogen receptor (ER) and/or progesterone receptor (PgR) ≥ 10 fmol/mg cytosol protein; or ≥ 10% of the tumor cells positive by immunocytochemical evaluation.

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Adequate bone marrow function (white blood cell count [WBC] > 3.0 x 109 /L, platelets ≥ 100.0 x 109 /L, and hemoglobin > 10 g/dL).
Documented evidence of adequate renal function (creatinine < 180 µmol/L) and hepatic function (bilirubin < 30 µmol/L, alanine aminotransferase (ALT) < 1.5 x upper normal limit of the laboratory).
Life expectancy of at least 24 months at the time of enrollment.
Written voluntary informed consent prior to initiation of any study procedure.
Willingness to undergo all scheduled tests and examinations for evaluation of bone density and bone metabolism, and lipid profiles in addition to the standard assessments for monitoring their breast cancer status.

Who cannot join

Patients with distant metastases as defined by the criteria of the Danish Breast Cancer Co-operative Group (DBCCOG).
Pre-existing bone disease (e.g. osteomalacia, osteogenesis imperfecta, Paget's disease).
Patients receiving bisphosphonates for more than 3 months before randomization.
Chronic treatment with drugs known to interfere with bone metabolism, e.g.
Anti-convulsants within the past year.
Corticosteroids at doses greater than the equivalent of 5 mg/day prednisone for more than two weeks in the past 6 months (prior to randomization).

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Any previous treatment with sodium fluoride at daily doses ≥ 5 mg/day for a period exceeding 1 month.
Anabolic steroids in the past 12 months.
Long term use of coumarin derivatives and heparin at the time of randomization.
Metabolic diseases known to interfere with bone metabolism (e.g., Hyperparathyroidism, hypoparathyroidism, uncontrolled thyroid disease, Cushing's disease, vitamin D deficiency, malabsorption syndrome, etc.).
Treatment with lipid-lowering agents within the 3 months prior to randomization (this exclusion criterion did not apply to patients randomized in the United Kingdom).
Patients receiving other anti-cancer treatment.
Previous neoadjuvant / adjuvant chemotherapy and /or previous adjuvant endocrine therapy (e.g., anti-estrogens, AIs).
History of previous or concomitant malignancy within the past 5 years other than adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix. Patients who had a previous other malignancy must have been disease free for five years. Patients with endometrial cancer and/or invasive breast cancer at any time in their medical history were excluded. Patients with invasive bilateral breast cancer were excluded. Patients with vaginal discharge/ vaginal bleeding with evidence of malignancy were excluded.
Any other non-malignant systemic diseases (cardiovascular, renal, hepatic, lung embolism, etc.) which would prevent prolonged follow-up.

Trial locations and contacts

13 sites in 2 countries.

Country

City, postcode or hospital

13 sites in 2 countries

Denmark12 sites

Novartis Investigative Site
Aalborg
Novartis Investigative Site
Aarhus
Novartis Investigative Site
Copenhagen
Novartis Investigative Site
Esbjerg
Novartis Investigative Site
Herlev
Novartis Investigative Site
Herning
Novartis Investigative Site
Hillerød
Novartis Investigative Site
Kløvervænget
Novartis Investigative Site
Roskilde
Novartis Investigative Site
Sønderborg
Novartis Investigative Site
Vejle
Novartis Investigative Site
Viborg

Other trials in Denmark

United Kingdom1 site

Novartis Investigative Site
Sheffield

Other trials in United Kingdom

About this study

Estrogen is known to be a regulator of bone and lipid metabolism. Letrozole is a potent inhibitor of estrogen synthesis.

This study evaluated the effects of letrozole and tamoxifen on bone and lipid metabolism in postmenopausal women with resected, receptor positive early breast cancer.

Conditions: Hormone Sensitive Resected Primary Breast Cancer in Postmenopausal Women
Being tested: Letrozole, Tamoxifen
Keywords: Breast Cancer, Letrozole, Bone Mineral Density, Bone Markers, Serum lipid, Postmenopausal
Medical subject headings: Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LetrozoleDrug
2.5 mg tablets and supplied in bottles with 6-monthly supplies.
TamoxifenDrug
20 mg tablets in bottles as 6-monthly supplies (supplied to Novartis as Tamofen from Schering Oy, Subsidiary of Schering AG, Pansiontie 47, FIN-2010 Turku, Finland)

Study groups in NCT00171704
Study group	Role	What they receive
Letrozole	Experimental	2.5 mg once daily (q.d.)orally for 5 years Receives: Drug: Letrozole
Tam-Let	Experimental	20 mg Tamoxifen once daily (q.d.) orally for 2 years followed by Letrozole 2.5 mg q.d. orally for 3 years. Receives: Drug: Letrozole; Drug: Tamoxifen

What is being measured

The primary outcome is the main question the study is designed to answer.

Percent Change From Baseline of Bone Mineral Density of the Lumbar Spine (L2-l4)
Lumbar spine (L2-L4) BMD measurements by dual energy X-ray absorptiometry (DXA) were performed after surgery and within 2 weeks prior to randomization and repeated every 6 months for the first 2 years and annually thereafter until 5 years after enrollment. The primary scanning site was the lumbar spine (L2 to L4) and the secondary scanning site was the total hip. All DXA scans were evaluated by a central reader.
Measured: Baseline, 24 months

Secondary outcomes (7)

Percent Change From Baseline of Bone Mineral Density of the Lumbar Spine
Lumbar spine (L2-L4)BMD measurements by dual energy X-ray absorptiometry (DXA) were performed after surgery and within 2 weeks prior to randomization and repeated every 6 months for the first 2 years and annually thereafter until 5 years after enrollment. The primary scanning site was the lumbar spine (L2 to L4) and the secondary scanning site was the total hip. All DXA scans were evaluated by a central reader.
Measured: Baseline, 60 months
Percent Change From Baseline of Bone Mineral Density (BMD) of Total Hip
Total hip BMD measurements by dual energy X-ray absorptiometry (DXA) were performed after surgery and within 2 weeks prior to randomization and repeated every 6 months for the first 2 years and annually thereafter until 5 years after enrollment. All DXA scans were evaluated by a central reader.
Measured: Baseline, 60 months
Median Percent Change From Baseline of Serum Markers of Bone Turnover
Bone turnover markers (fasting serum procollagen-I extension peptide [P1NP], C-telopeptide [CTX], skeletal bone-specific alkaline phosphatase [BSAP, N-telopeptide [NTX]) were measured at baseline/screening and at each visit thereafter. A central laboratory was used to analyze the samples. The analysis of bone markers was based on analysis of variance of the regression slopes calculated for each individual patient and each bone marker over time. In the following summary, only the median treatment group percent change from baseline (and range) at 5 years is presented for each bone marker.
Measured: Baseline, 60 months
Percentage Change From Baseline in Serum Lipids at 5 Years
Serum lipid profile (fasting serum cholesterol [total, HDL and calculated LDL], triglycerides, and lipoprotein [a]) were measured at baseline/screening and at each visit thereafter. A central laboratory was used to analyze the samples. The analysis of serum lipids was on the treatment group median percent change from baseline (and range) at 5 years.
Measured: Baseline, 60 months
Number of Participants With Clinically Relevant Changes From Baseline in Cholesterol
Serum lipid profile (fasting serum cholesterol [total, HDL and calculated LDL], triglycerides, and lipoprotein [a]) were measured at baseline/screening and at each visit thereafter. A central laboratory was used to analyze the samples. Numbers are not additive, as patients could be included in multiple rows.
Measured: Baseline, 60 months
Time to Disease Recurrence or Death
Disease-free survival was defined as the interval between randomization and earliest confirmed event of loco-regional recurrence, distant metastases, invasive contralateral breast cancer, or death from any cause.
Measured: 60 months
Time to Overall Survival Events
Overall survival was measured from date of randomization to date of death.
Measured: 60 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2005Mar 2011

First posted15 Sep 2005 (estimated)
Study startApr 2005
Primary completionMar 2011
Study completionMar 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Hormone Sensitive Resected Primary Breast Cancer in Postmenopausal WomenStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 263 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00171704
Sponsor's protocol ID: CFEM345D2407
Status last verified: May 2012
First submitted: 13 Sep 2005
Last updated: 3 Mar 2017
Results posted: Yes, on ClinicalTrials.gov

Study at a glance

From the registry record, last updated by the sponsor on 3 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Study to Evaluate the Effect of Letrozole and Tamoxifen on Bone and Lipids in Postmenopausal Women With Breast Cancer
ClinicalTrials.gov ID: NCT00171704
Acronym / sponsor ID: CFEM345D2407
Conditions: Hormone Sensitive Resected Primary Breast Cancer in Postmenopausal Women
Keywords: Breast Cancer, Letrozole, Bone Mineral Density, Bone Markers, Serum lipid, Postmenopausal
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 263 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Collaborators: Danish Breast Cancer Cooperative Group, University of Sheffield
Study start: Apr 2005
Primary completion: Mar 2011 (actual)
Study completion: Mar 2011 (actual)
First posted: 15 Sep 2005 (estimated)
Results: Posted 4 Jun 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Estrogen is known to be a regulator of bone and lipid metabolism. Letrozole is a potent inhibitor of estrogen synthesis.

This study evaluated the effects of letrozole and tamoxifen on bone and lipid metabolism in postmenopausal women with resected, receptor positive early breast cancer.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Letrozole	Experimental	Drug: Letrozole2.5 mg once daily (q.d.)orally for 5 years
Tam-Let	Experimental	Drug: Letrozole, Drug: Tamoxifen20 mg Tamoxifen once daily (q.d.) orally for 2 years followed by Letrozole 2.5 mg q.d. orally for 3 years.

Who may qualify

Ages: 50 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

Female
Post-menopausal hormone status defined as:
Patients with menostasis (amenorrhea) > 12 months or history of oophorectomy.
Patients ≥ 55 years with history of hysterectomy or having continued/renewed menstruation on cyclic hormone treatment.
Patients of 50-54 years: Menopausal status was determined on the basis of follicle-stimulating hormone (FSH)/luteinizing hormone (LH) values.

Key exclusion criteria (15 listed)

Patients with distant metastases as defined by the criteria of the Danish Breast Cancer Co-operative Group (DBCCOG).
Pre-existing bone disease (e.g. osteomalacia, osteogenesis imperfecta, Paget's disease).
Patients receiving bisphosphonates for more than 3 months before randomization.
Chronic treatment with drugs known to interfere with bone metabolism, e.g.
Anti-convulsants within the past year.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Letrozole2.5 mg tablets and supplied in bottles with 6-monthly supplies.	Drug	Letrozole, Tam-Let
Tamoxifen20 mg tablets in bottles as 6-monthly supplies (supplied to Novartis as Tamofen from Schering Oy, Subsidiary of Schering AG, Pansiontie 47, FIN-2010 Turku, Finland)	Drug	Tam-Let

Primary outcome

Percent Change From Baseline of Bone Mineral Density of the Lumbar Spine (L2-l4)
Time frame: Baseline, 24 months
Lumbar spine (L2-L4) BMD measurements by dual energy X-ray absorptiometry (DXA) were performed after surgery and within 2 weeks prior to randomization and repeated every 6 months for the first 2 years and annually thereafter until 5 years after enrollment. The primary scanning site was the lumbar spine (L2 to L4) and the secondary scanning site was the total hip. All DXA scans were evaluated by a central reader.

7 secondary outcomes

Percent Change From Baseline of Bone Mineral Density of the Lumbar Spine
Time frame: Baseline, 60 months
Percent Change From Baseline of Bone Mineral Density (BMD) of Total Hip
Time frame: Baseline, 60 months
Median Percent Change From Baseline of Serum Markers of Bone Turnover
Time frame: Baseline, 60 months
Percentage Change From Baseline in Serum Lipids at 5 Years
Time frame: Baseline, 60 months
Number of Participants With Clinically Relevant Changes From Baseline in Cholesterol
Time frame: Baseline, 60 months
Time to Disease Recurrence or Death
Time frame: 60 months
Time to Overall Survival Events
Time frame: 60 Months

Results and safety

Results posted to the registry on 4 Jun 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Letrozole	133	89
Tam-Let	130	81

Primary outcome: Percent Change From Baseline of Bone Mineral Density of the Lumbar Spine (L2-l4)

Time frame: Baseline, 24 months. Median (Full Range). Unit: Percent Change

Measure	Letrozole n = 63	Tam-Let n = 68
Value	-4.63 (-14.21 to 4.32)	0.37 (-6.98 to 15.21)

Population analysed: The safety population consisted of only patients who took randomized therapy for at least one day. The number of patients in each treatment arm who had completed 2 years of the study and had centrally assessed measurements of lumbar spine or total hip BMD.

7 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Letrozole	50 of 133 (37.6%)	113 of 133 (85%)	Not reported
Tam-Let	41 of 130 (31.5%)	110 of 130 (84.6%)	Not reported

Limitations and caveats (from the sponsor): The study was designed to investigate the effects of letrozole compared with tamoxifen for 2 years on BMD spine (L2-L4). The study was too small to investigate the comparative efficacy of treatments on disease-free survival or on overall survival.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis study chair

Novartis

13 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Letrozole and Tamoxifen in people with Hormone Sensitive Resected Primary Breast Cancer in Postmenopausal Women, run by Novartis Pharmaceuticals at 13 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Denmark, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Jun 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline of Bone Mineral Density of the Lumbar Spine (L2-l4) (time frame: Baseline, 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00171704.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2017.