Breast CancerPhase 3GIM4NCT01064635
Letrozole in Treating Breast Cancer in Postmenopausal Women With Stage I, II, or III Breast Cancer Previously Treated With Tamoxifen (GIM4)
A Phase 3 study testing Letrozole in people with Breast Cancer, run by IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy at 1 site in Italy.
Trial summary
RATIONALE: Estrogen can cause the growth of breast cancer cells. Letrozole may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known which regimen of letrozole is most effective in treating breast cancer in postmenopausal women who have received tamoxifen. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Letrozole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,056 participants
- Where
- 1 siteItaly
- Study dates
- Aug 2005to Aug 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent prior to beginning protocol specific procedures.
- Histologically proven breast cancer at the first diagnosis with tumor stage I-II-III. Patients with histologically documented (microscopic) infiltration of the skin (pT4) will also be eligible.
- Axillary Nodal status allowed: Nx, pNo, pN1, pN2, pN3.
- Postmenopausal status defined by one of the following:
- Age > 55 years with cessation of menses
- Age < 55 years but not spontaneous menses for at least 1 year
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- Age < 55 years and spontaneous menses within the past 1 year, but currently amenorrheic (e.g. spontaneous, or secondary to hysterectomy), AND with postmenopausal gonadotrophin levels (luteinizing hormone and follicle stimulating hormone levels >40 IU/L) or postmenopausal estradiol levels (<5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory involved.
- Bilateral oophorectomy
- Adjuvant TAM received for at least 2 years and not more than 3 years and 3 months. Patients treated with adjuvant chemotherapy, are required to have begun receiving TAM within 3 months after the completion of chemotherapy.
- Definitive surgical treatment must be either mastectomy or breast conserving surgery, with axillary lymph node dissection or sentinel node biopsy for operable breast cancer.
- ECOG/WHO performance Status 0-1. Patients must be accessible for treatment and follow-up.
- Concomitant treatment with biphosphonates are allowed and should be recorded during the trial.
Who cannot join
- Male patients.
- Any locally advanced (T4) or inflammatory breast cancer. However, patients with microscopic infiltration of the skin (pT4) will be eligible.
- Patients with distant metastases. Any suspicious manifestation requires appropriate investigation to exclude metastases.
- Histology other than adenocarcinoma.
- Patients with previous or concomitant (not breast cancer) malignancy within the past 5 years EXCEPT adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix. Patients who have had a previous other malignancy must have been disease free for 5 years.
- Patients with other non-malignant systemic diseases (cardiovascular, renal, hepatic, lung embolism, etc.) which would prevent prolonged follow-up.
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- Use of hormone Replacement Therapy within four weeks before randomization.
- Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational regimen within 30 days prior to study entry.
- Concurrent treatment with any other anti-cancer therapy.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Letrozole Adjuvant Therapy Duration (LEAD) Study: Standard Versus Long Treatment. A Phase III Trial in Post-Menopausal Women With Early Breast Cancer.
RATIONALE: Estrogen can cause the growth of breast cancer cells. Letrozole may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known which regimen of letrozole is most effective in treating breast cancer in postmenopausal women who have received tamoxifen.
PURPOSE: This randomized phase III trial is comparing different regimens of letrozole to see how well they work in treating postmenopausal women with stage I, stage II, or stage III breast cancer previously treated with tamoxifen.
Read the detailed description
OBJECTIVES:
Primary
- To compare the disease-free survival of previously treated, post-menopausal women with early-stage breast cancer treated with standard- (2-3 years of tamoxifen followed by 2-3 years of letrozole) versus long-treatment (2-3 years of tamoxifen followed by 5 years of letrozole) adjuvant letrozole.
Secondary
- To compare the overall survival of these patients.
- To compare the safety of these patients.
OUTLINE: Patients are randomized to 1 or 2 treatment arms.
- Arm I (standard treatment): Patients previously treated with tamoxifen for 2 years receive letrozole for an additional 3 years; patients previously treated with tamoxifen for 3 years receive letrozole for an additional 2 years; and patients previously treated with tamoxifen for 2-3 years receive letrozole , so the total duration of the endocrine treatment (i.e., tamoxifen followed by letrozole) is 5 years.
- Arm II (long treatment): Patients receive letrozole for an additional 5 years regardless of the duration of the previous tamoxifen treatment.
- Conditions
- Breast Cancer
- Being tested
- Letrozole
- Keywords
- stage IA breast cancer, stage IB breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Letrozole for 3-2 years | Active comparator | Patients pre-treated with TAM for 2-3 years will receive letrozole 2,5 mg/die for 3-2 years. Total duration of early adjuvant endocrine therapy: 5 years Receives: Drug: Letrozole |
| Letrozole for 5 year | Experimental | Patients pre-treated with TAM for 2-3 years will receive letrozole 2,5 mg/die for additional 5 years. Total duration of early adjuvant endocrine therapy: 7 years for patients pretreated with 2 years of TAM and 8 years for patients pre-treated with 3 years of TAM Receives: Drug: Letrozole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-free survival
Measured: 6 years after the last patient enters the study
Secondary outcomes (2)
Overall survival
Measured: 6 years after the last patient enters the study
Safety
Measured: 6 years after the last patient enters the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2010 (estimated)
- Study startAug 2005
- Primary completionAug 2015
- Study completionAug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- 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
- 2,056 participants (actual)
Sponsor and investigators
- Lead sponsor
- IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lucia Del Mastro,MD, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
- Investigators
- Lucia Del Mastro, MD, Principal investigator, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01064635
- Sponsor's protocol ID
- CDR0000665188
- Other IDs
- GIM-4-LEAD, 2005-001212-44, EU-21003, 2005
- Acronym
- GIM4
- Status last verified
- May 2024
- First submitted
- 5 Feb 2010
- Last updated
- 8 May 2024
- Results posted
- No
Publications
Del Mastro L, Mansutti M, Bisagni G, Ponzone R, Durando A, Amaducci L, Campadelli E, Cognetti F, Frassoldati A, Michelotti A, Mura S, Urracci Y, Sanna G, Gori S, De Placido S, Garrone O, Fabi A, Barone C, Tamberi S, Bighin C, Puglisi F, Moretti G, Arpino G, Ballestrero A, Poggio F, Lambertini M, Montemurro F, Bruzzi P; Gruppo Italiano Mammella investigators. Extended therapy with letrozole as adjuvant treatment of postmenopausal patients with early-stage breast cancer: a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Oct;22(10):1458-1467. doi: 10.1016/S1470-2045(21)00352-1. Epub 2021 Sep 17.
PubMed 34543613
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Letrozole Adjuvant Therapy Duration (LEAD) Study: Standard Versus Long Treatment. A Phase III Trial in Post-Menopausal Women With Early Breast Cancer.
- ClinicalTrials.gov ID
- NCT01064635
- Acronym / sponsor ID
- GIM4 / CDR0000665188
- Conditions
- Breast Cancer
- Keywords
- stage IA breast cancer, stage IB breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 2,056 participants (actual)
- Lead sponsor
- IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, ItalyUniversity, hospital or other
- Study start
- Aug 2005
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2026 (estimated)
- First posted
- 8 Feb 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Estrogen can cause the growth of breast cancer cells. Letrozole may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known which regimen of letrozole is most effective in treating breast cancer in postmenopausal women who have received tamoxifen.
PURPOSE: This randomized phase III trial is comparing different regimens of letrozole to see how well they work in treating postmenopausal women with stage I, stage II, or stage III breast cancer previously treated with tamoxifen.
Detailed description
OBJECTIVES:
Primary
- To compare the disease-free survival of previously treated, post-menopausal women with early-stage breast cancer treated with standard- (2-3 years of tamoxifen followed by 2-3 years of letrozole) versus long-treatment (2-3 years of tamoxifen followed by 5 years of letrozole) adjuvant letrozole.
Secondary
- To compare the overall survival of these patients.
- To compare the safety of these patients.
OUTLINE: Patients are randomized to 1 or 2 treatment arms.
- Arm I (standard treatment): Patients previously treated with tamoxifen for 2 years receive letrozole for an additional 3 years; patients previously treated with tamoxifen for 3 years receive letrozole for an additional 2 years; and patients previously treated with tamoxifen for 2-3 years receive letrozole , so the total duration of the endocrine treatment (i.e., tamoxifen followed by letrozole) is 5 years.
- Arm II (long treatment): Patients receive letrozole for an additional 5 years regardless of the duration of the previous tamoxifen treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Letrozole for 3-2 years | Active comparator | Drug: LetrozolePatients pre-treated with TAM for 2-3 years will receive letrozole 2,5 mg/die for 3-2 years. Total duration of early adjuvant endocrine therapy: 5 years |
| Letrozole for 5 year | Experimental | Drug: LetrozolePatients pre-treated with TAM for 2-3 years will receive letrozole 2,5 mg/die for additional 5 years. Total duration of early adjuvant endocrine therapy: 7 years for patients pretreated with 2 years of TAM and 8 years for patients pre-treated with 3 years of TAM |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Signed informed consent prior to beginning protocol specific procedures.
- Histologically proven breast cancer at the first diagnosis with tumor stage I-II-III. Patients with histologically documented (microscopic) infiltration of the skin (pT4) will also be eligible.
- Axillary Nodal status allowed: Nx, pNo, pN1, pN2, pN3.
- Postmenopausal status defined by one of the following:
- Adjuvant TAM received for at least 2 years and not more than 3 years and 3 months. Patients treated with adjuvant chemotherapy, are required to have begun receiving TAM within 3 months after the completion of chemotherapy.
Key exclusion criteria (9 listed)
- Male patients.
- Any locally advanced (T4) or inflammatory breast cancer. However, patients with microscopic infiltration of the skin (pT4) will be eligible.
- Patients with distant metastases. Any suspicious manifestation requires appropriate investigation to exclude metastases.
- Histology other than adenocarcinoma.
- Patients with previous or concomitant (not breast cancer) malignancy within the past 5 years EXCEPT adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix. Patients who have had a previous other malignancy must have been disease free for 5 years.
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 |
|---|---|---|
| Letrozoleletrozole for 2-3 years after Tam | Drug | Letrozole for 3-2 years |
| LetrozoleLetrozole for 5 years after Tam | Drug | Letrozole for 5 year |
Primary outcome
Disease-free survival
Time frame: 6 years after the last patient enters the study
2 secondary outcomes
Overall survival
Time frame: 6 years after the last patient enters the study
Safety
Time frame: 6 years after the last patient enters the study
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2024.
- Derived from this study: PubMed 34543613Del Mastro L, Mansutti M, Bisagni G, Ponzone R, Durando A, Amaducci L, Campadelli E, Cognetti F, Frassoldati A, Michelotti A, Mura S, Urracci Y, Sanna G, Gori S, De Placido S, Garrone O, Fabi A, Barone C, Tamberi S, Bighin C, Puglisi F, Moretti G, Arpino G, Ballestrero A, Poggio F, Lambertini M, Montemurro F, Bruzzi P; Gruppo Italiano Mammella investigators. Extended therapy with letrozole as adjuvant treatment of postmenopausal patients with early-stage breast cancer: a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Oct;22(10):1458-1467. doi: 10.1016/S1470-2045(21)00352-1. Epub 2021 Sep 17.
- Clinical trial summary from the National Cancer Institute's PDQ® databaseLink provided by the sponsor.
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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.
Lucia Del Mastro, MD principal investigator
IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Letrozole in people with Breast Cancer, run by IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy at 1 site in Italy.
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 12 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 8 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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?
Results are not available in the source record.
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?
Disease-free survival (time frame: 6 years after the last patient enters the study). 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 NCT01064635, which also lists 1 linked publication.
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 8 May 2024.