Letrozole in Treating Breast Cancer in Postmenopausal Women With Stage I, II, or III Breast Cancer Previously Treated With Tamoxifen (GIM4)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Lucia Del Mastro,MD, National Institute for Cancer Research, Italy
ClinicalTrials.gov Identifier:
NCT01064635
First received: February 5, 2010
Last updated: May 22, 2015
Last verified: May 2015
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: Letrozole
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Letrozole Adjuvant Therapy Duration (LEAD) Study: Standard Versus Long Treatment. A Phase III Trial in Post-Menopausal Women With Early Breast Cancer.

Resource links provided by NLM:


Further study details as provided by National Institute for Cancer Research, Italy:

Primary Outcome Measures:
  • Disease-free survival [ Time Frame: 6 years after the last patient enters the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: 6 years after the last patient enters the study ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: 6 years after the last patient enters the study ] [ Designated as safety issue: Yes ]

Enrollment: 2056
Study Start Date: August 2005
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Letrozole for 3-2 years
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
Drug: Letrozole
letrozole for 2-3 years after Tam
Experimental: Letrozole for 5 year
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
Drug: Letrozole
Letrozole for 5 years after Tam

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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 gonatrophin 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01064635

Locations
Italy
Istituto Nazionale per la Ricerca sul Cancro
Genoa, Italy, 16132
Sponsors and Collaborators
National Institute for Cancer Research, Italy
Investigators
Principal Investigator: Lucia Del Mastro, MD National Institute for Cancer Research, Italy
  More Information

Additional Information:
No publications provided

Responsible Party: Lucia Del Mastro,MD, Principal Invesitagator, National Institute for Cancer Research, Italy
ClinicalTrials.gov Identifier: NCT01064635     History of Changes
Other Study ID Numbers: CDR0000665188, GIM-4-LEAD, 2005-001212-44, EU-21003
Study First Received: February 5, 2010
Last Updated: May 22, 2015
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by National Institute for Cancer Research, Italy:
stage IA breast cancer
stage IB breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Letrozole
Antineoplastic Agents
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015