Hormone Receptor Positive Breast Cancer
Conditions
Interventions
Trade Name: Femara
Product Name: Letrozole
Pharmaceutical Form: Tablet
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Tabl
Sponsors
ICORG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1- The patient must have consented to participate and must have signed and dated an appropriate IRB-approved consent form . 2- Patients must be female. 3- Patients must have an ECOG performance status of 0 or 1 (0 = fully active, able to carry on all pre-disease performance without restriction; 1 = restricted in physically strenuous activity but ambulatory). 4- Patients must be postmenopausal at the time of randomization. (Note: Premenopausal or perimenopausal women requiring therapy with luteinising hormone-releasing hormone [LHRH] analogs to suppress ovarian function are not eligible.) For study purposes, postmenopausal is defined as: • age 56 or older with no spontaneous menses for at least 12 months prior to study entry, or • age 55 or younger with no spontaneous menses for at least 12 months prior to study entry (e.g., spontaneous or secondary to hysterectomy) AND with a documented estradiol level in the postmenopausal range according to local institutional/laboratory standards, or • a prior documented bilateral oophorectomy. 5- The patient must have remained disease-free from the time of initial breast cancer diagnosis until the time of randomization. 6- The primary tumor must have been pathologic or clinical stage I, II, or IIIA invasive carcinoma of the breast documented by core needle or open biopsy. 7- The primary tumor must have been ER-positive and/or PgR-positive. (Patients who had a tumor that was considered to be borderline for ER positivity and who were treated with tamoxifen and/or an AI are eligible for this study.) 8- Patients must have undergone either a lumpectomy with axillary nodal staging followed by breast radiotherapy or a total mastectomy with axillary nodal staging. (Acceptable axillary nodal staging procedures include sentinel node biopsy alone, if sentinel nodes were negative on H&E staining.) 9- The duration of the patient's hormonal therapy following breast cancer diagnosis must have been 57-63 months from the first dose regardless of the number of missed doses. Hormonal therapy must have consisted of an AI or a combination of up to 3 years of tamoxifen followed by an AI. Tamoxifen may not have been given during years 4 and 5 of the 5 years of adjuvant hormonal therapy. Optional Letrozole Registration Program for patients who have not yet completed 5 years of hormonal therapy: In order to have a predominantly letrozole-treated population for B-42 study entry, patients who have had a minimum of 2 years of hormonal therapy and who are currently on tamoxifen (for up to 3 years) or an AI may be offered letrozole at no cost until they complete 5 total years of initial adjuvant hormonal therapy. See Appendix A for instructions on enrolling patients on this optional Letrozole Registration Program. 10- B-42 randomization must be within 6 months following completion of 5 years of initial adjuvant hormonal therapy. 11- At the time of randomization, the patient must have had the following: • history and physical exam within 3 months demonstrating no findings suggestive of recurrent breast cancer; • bilateral mammogram within 1 year (unilateral if patient had a mastectomy); • bone mineral density (BMD) testing within 1 year; and • lipid profile (total cholesterol, LDL-C, HDL-C, and triglycerides) with a total cholesterol value = grade 1 (according to CTCAE v3.0), with or without cholesterol-lowering therapy. - within 1 year if the patient has a history of hypercholesterolemia con
Exclusion criteria
Exclusion criteria: 1- History of non-traumatic osteoporotic fracture of wrist, hip, or spine. 2- Diagnosis of contralateral breast cancer including DCIS. 3- Other malignancies unless the patient is considered to be disease-free for 5 or more years prior to randomization, and is deemed by their physician to be at low risk for recurrence. Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: carcinoma in situ of the cervix, colon carcinoma in situ, melanoma in situ, and basal cell and squamous cell carcinoma of the skin. 4- Sex hormonal therapy, e.g., estrogen- or progesterone-replacement therapy or oral contraceptives. These patients are eligible only if this therapy is discontinued prior to randomization. 5- Therapy with any hormonal agent such as raloxifene for management of osteoporosis. Patients are eligible only if these medications are discontinued prior to study entry. 6- Administration of any investigational agent within 30 days before study entry. In addition to the formal eligibility/ineligibility criteria investigators should consider each of these factors when selecting patients for B-42: • Patients with a life expectancy less than 10 years, excluding her diagnosis of breast cancer. (Comorbid conditions should be taken into consideration, but not the diagnosis of breast cancer.) • Patients who have demonstrated poor compliance with previous AI or tamoxifen and AI therapy. (Note: Patients may have had drug holidays, as long as the frequency or duration of the drug holidays does not indicate to the investigator that the patient will not be compliant with taking study drug for 5 years.) • Patients for whom bisphosphonate therapy is not recommended or not tolerated. (Note: Bisphosphonate therapy is a recommended intervention in the B-42 osteoporosis management instructions.) • Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary aim is to determine whether or not prolonged adjuvant hormonal therapy with letrozole will improve disease-free survival in postmenopausal women with ER-positive and/or PgR-positive tumors who have completed 5 years of hormonal therapy with 5 years of an aromatase inhibitor (AI) or 5 years of a combination of up to 3 years of tamoxifen followed by an AI.;Secondary Objective: Survival (S) Determine whether or not prolonged adjuvant hormonal therapy with letrozole will improve survival. Breast cancer-free interval: Determine whether or not prolonged adjuvant hormonal therapy with letrozole will improve breast cancer-free survival. Distant recurrence Determine whether or not prolonged hormonal therapy with letrozole will improve distant recurrence. Osteoporotic-related fractures (Colles', hip, and spine) Determine whether or not prolonged adjuvant hormonal therapy with letrozole will increase osteoporotic-related fractures (Colles', hip, and spine). Arterial thrombotic events Determine whether or not prolonged adjuvant hormonal therapy with letrozole will increase arterial thrombotic events. ;Primary end point(s): The primary endpoint for analysis is disease-free survival (DFS). DFS events are local recurrence following mastectomy, local recurrence in the ipsilateral breast following lumpectomy (IBTR), regional recurrence, distant recurrence, second primary cancer (other than squamous and basal cell carcinoma of the skin, melanoma in situ, and carcinoma in situ of the colon and cervix), and death from any cause prior to recurrence or second primary cancer. | — |
Countries
Ireland
Outcome results
None listed