Randomized, double-blind, multicentric phase III trial evaluating the safety and benefit of adding everolimus to adjuvant hormone therapy in women with poor prognosis, ER+ and HER2- primary breast cancer who remain free of disease after receiving 3 years of adjuvant hormone therapy
- Conditions
- women with poor prognosis, ER+ and HER2- primary breast cancer who remain free of disease after receiving 3 years of adjuvant hormone therapyTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-003187-44-FR
- Lead Sponsor
- ICANCER
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 1984
1.Women = 18 years of age,
2.Histologically proven invasive unilateral or bilateral breast cancer (regardless of the type),
3.Any T, M0
4.At least 4 positive lymph nodes if initial surgery, or at least 1 positive lymph node after neo-adjuvant chemotherapy or hormone therapy
5.ER+ and HER2 negative : Hormone receptor positive is defined as any staining on the primary tumor, HER2 negativity is defined as IHC 0-1+, or [IHC 2+ and FISH or CISH negative]
6.Initial tumor completely resected (surgery could have been done before or after neoadjuvant chemotherapy/hormone therapy)
7.Having received at least 2 years and 10 months but not more than 3 years and 6 months of adjuvant hormone therapy. Hormone therapy could be either tamoxifen, letrozol, anastrozol or exemestane.
8.No clinically or radiologically detectable metastases at time of inclusion.
9.WHO Performance status (ECOG) of 0 or 1.
10.Adequate hematological function (neutrophil count = 2x109/l, platelet count = 100x 109/l)
11.Adequate hepatic function: ASAT and ALAT = 2.5 ULN, alkaline phosphatases = 2.5 ULN, total bilirubin = 2 ULN.
12.Adequate renal function: serum creatinine = 1.5 ULN.
13.Signed written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1.Any local, regional or metastatic evolution.
2.Any clinically or radiologically suspect and non-explored damage to the contra lateral breast.
3.Previous cancer (excepted cutaneous baso-cellular epithelioma or uterin peripheral ephitelioma) in the preceding 5 years, including invasive controlateral breast cancer.
4.Patients already included in another ongoing therapeutic trial involving an experimental drug for which follow-up is required.
5.Pregnant or breast-feeding patients. Adequate birth control measures should be taken during study treatment phase.
6.Patients with severely impaired lung function (e.g. Chronic Obstructive Pulmonary Disease, respiratory insufficiency, Interstitial Lung Disease)
7.Positive serology for HIV infection or hepatitis C.
8.Chronic carrier of HBV (positive Antigen HbS in the blood)
9.Patients with chronic infection
10.Uncontrolled diabetes defined as glycated haemoglobinemia >7%
11.Uncontrolled hypercholesterolemia (cholesterol >400 mg/dl under adequate therapy).
12.Patients with other concurrent severe and/or uncontrolled medical disease or infection which could compromise participation in the study.
13.Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the benefit from adding everolimus to standard endocrine treatments after two years of treatment on the disease-free survival (DFS) after randomization.;<br> Secondary Objective: 1 - efficacy :<br> 2 - toxicity :<br> 3 - biology :<br> 4 –quality of life sub-studies<br> ;Primary end point(s): Disease free survival rate (DFS) after randomization (disease is defined as a local, regional or metastatic relapse, a contralateral breast cancer, or a death of any cause).;Timepoint(s) of evaluation of this end point: Using an inclusion period of 3 years and a minimum follow-up duration of 2 years for the last included patient, (which correspond to 5 years study duration), 286 events would be observed at the time of the final analysis
- Secondary Outcome Measures
Name Time Method <br> Secondary end point(s): 1.Efficacy :<br> - Overall survival rate (OS) for the whole population,<br> - DFS and OS for ER+ and PR+ subgroup<br> - DFS and OS for the remainder ER+/PR – subgroup<br> - EFS<br> - DMFS<br> - Secondary cancer<br> 2.Toxicity<br> - CTC-AE scale version 4.0.<br> 3.Biotheque<br> - IHC Analysis<br> 4.Quality of life<br> - QlQ C30.<br>