Safety Study of Adding Everolimus to Adjuvant Hormone Therapy in Women With Poor Prognosis, ER+ and HER2- Primary Breast Cancer, Free of Disease After Receiving 3 Years of Adjuvant Hormone Therapy
A significant number of patients relapse and eventually die, particularly if they were initially diagnosed with large nodes involvement and/or T3/4 diseases. When analyses focus on patients with ER+/Her2-negative breast cancer, with ≥4N+, 30% had relapsed at 5 years, emphasizing the need for new drugs in this setting (PACS01 data, UNICANCER internal data).
Strong evidence suggests that cross-talk between the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway and ER signaling is linked to hormone resistance in breast cancer patients.
In the present study, we plan to evaluate the benefit from adding everolimus to standard endocrine treatments after three years of treatment for patient ER+/HER2- at high risk of relapse due to high nodes involvement (≥4) and/or persistent node involvement after neo-adjuvant chemotherapy.
This study is a unique opportunity to prove the efficacy of everolimus in adjuvant setting. The study could be practice changing in case of positive results and could allow improving outcome of breast cancer patients presenting high risk of metastatic relapse.
ER-positive HER2-negative Breast Cancer
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||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|
- To evaluate the benefit from adding everolimus to standard endocrine treatments after two years of treatment on the disease-free survival (DFS) after randomization. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Assessment of impact of everolimus on the overall survival (OS), the Event Free Survival (EFS) and Distant Metastasis Free Survival (DMFS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Assessment of impact of everolimus on DFS and OS in ER+,PR+ and ER+/PR- subgroups [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Impact of everolimus on the incidence of secondary cancers [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Assessment of the safety profiles for everolimus and hormone therapy combination. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Biology: Predictive value of mTOR activation markers on DFS: IHC analysis of primary tumor for pS6K and p4EBP. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- quality of life sub-studies [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||March 2013|
|Estimated Study Completion Date:||January 2018|
|Estimated Primary Completion Date:||January 2018 (Final data collection date for primary outcome measure)|
2 tablets/day (i.e.10mg/day )
(10mg/day, i.e. 2 tablets/day)
Other Name: Afinitor
Placebo Comparator: Placebo
|Contact: Jerome LEMONNIER, PhD||+33 1 7193 email@example.com|
|Centre Leon Berard||Recruiting|
|Principal Investigator: Thomas Bachelot|
|Principal Investigator: Fabrice Andre|
|Principal Investigator:||Thomas Bachelot, MD, PhD||Centre Leon Berard, Lyon, France|
|Principal Investigator:||Fabrice Andre, MD, PhD||Institut Gustave Roussy, Villejuif, France|