A Phase II, Randomized, Multi-center Study, Assessing Value of Adding Everolimus (RAD001) to Trastuzumab as Preoperative Therapy of HER-2 Positive Primary Breast Cancer Amenable to Surgery.
- To evaluate the added efficacy obtained by the association of trastuzumab (Herceptin®)
with everolimus as preoperative therapy of primary HER2-positive breast cancer as shown
by increased clinical tumor response rate.
- To compare the inhibition of the two pathways, RAS/RAF/MAP kinase and
- To evaluate whether the pre-treatment molecular characteristics of tumor and serum or
their modifications early in the treatment are predictive of clinical response.
- To compare the frequency of pathological complete response achieved in the two groups
after 6 weeks of treatment.
- To determine disease-free survival at 3 years.
- To evaluate safety and tolerability of the two treatment regimens.
- To analyze the possible relationships between treatment toxicity and constitutional
gene polymorphisms linked to the administered agents.
- To analyze the possible relationships between response and molecular pharmacodynamic
assessments, including proteomics (blood samples), Bio-Plex protein array (tumor), and
- To analyze the drug levels and pharmacokinetic assessments of everolimus and
OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive trastuzumab (Herceptin®) IV once weekly for 6 weeks. Patients
then undergo surgery.
- Arm II: Patients receive trastuzumab as in arm I and oral everolimus once daily for 6
weeks. Within 24 hours after completing everolimus, patients undergo surgery.
Blood and tumor samples are collected periodically during study for pharmacogenomic,
proteomic, and pharmacokinetic studies.
After completion of study treatment, patients are followed periodically for up to 3 years.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Efficacy as measured by clinical and echographic tumor evaluation
Mario Campone, MD
Centre Regional Rene Gauducheau
France : AFSSAPS (Agence Française de Sécurité Sanitaire des Produits de Santé)