Clinical trial NCT01064635: Letrozole in Treating Breast Cancer in Postmenopausal Women With Stage I, II, or III Breast Cancer Previously Treated With Tamoxifen (GIM4)
Official title: Letrozole Adjuvant Therapy Duration (LEAD) Study: Standard Versus Long Treatment. A Phase III Trial in Post-Menopausal Women With Early Breast Cancer.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
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
Lead sponsor: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Sponsor class: OTHER
First posted: 2010-02-08
Enrollment: 2056
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: INCLUSION CRITERIA

* 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
  * 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.

EXCLUSION CRITERIA

* 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.
* 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.

Primary outcomes:
measure: Disease-free survival
timeFrame: 6 years after the last patient enters the study
Secondary outcomes:
measure: Overall survival
timeFrame: 6 years after the last patient enters the study
measure: Safety
timeFrame: 6 years after the last patient enters the study
Other outcomes:
Locations:
city: Genoa
country: Italy
facility: Istituto Nazionale per la Ricerca sul Cancro
Study officials:
affiliation: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
name: Lucia Del Mastro, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.