Trastuzumab With or Without Everolimus in Treating Women With Breast Cancer That Can Be Removed By Surgery
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT00674414
- Lead Sponsor
- UNICANCER
- Brief Summary
RATIONALE: Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether giving everolimus together with trastuzumab is more effective than giving trastuzumab alone in treating women with breast cancer.
PURPOSE: This randomized phase II trial is studying trastuzumab and everolimus to see how well they work compared to trastuzumab alone before surgery in treating patients with breast cancer that can be removed by surgery.
- Detailed Description
OBJECTIVES:
Primary
* 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.
Secondary
* To compare the inhibition of the two pathways, RAS/RAF/MAP kinase and PI3-kinase/AKT/mTor.
* 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 IHC (tumor).
* To analyze the drug levels and pharmacokinetic assessments of everolimus and trastuzumab (Herceptin®).
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Female
- Target Recruitment
- 82
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I trastuzumab Patients receive trastuzumab (Herceptin®) IV once weekly for 6 weeks. Patients then undergo surgery. Arm I therapeutic conventional surgery Patients receive trastuzumab (Herceptin®) IV once weekly for 6 weeks. Patients then undergo surgery. Arm II trastuzumab Patients receive trastuzumab as in arm I and oral everolimus once daily for 6 weeks. Within 24 hours after completing everolimus, patients undergo surgery. Arm II everolimus Patients receive trastuzumab as in arm I and oral everolimus once daily for 6 weeks. Within 24 hours after completing everolimus, patients undergo surgery. Arm II therapeutic conventional surgery Patients receive trastuzumab as in arm I and oral everolimus once daily for 6 weeks. Within 24 hours after completing everolimus, patients undergo surgery.
- Primary Outcome Measures
Name Time Method Efficacy as measured by clinical and echographic tumor evaluation january 2013
- Secondary Outcome Measures
Name Time Method Disease-free survival at 3 years January 2015 Pathological response assessed after 6 weeks of treatment January 2013 Clinical response predictive factors May 2013 Rate of pathological complete response (pCR) January 2013 Pharmacogenomics, proteomics, immunohistochemistry (IHC), pharmacokinetics december 2013 Toxicity as assessed by the standard NCI CTC-AE v3.0 scale January 2013
Trial Locations
- Locations (8)
Centre Antoine Lacassagne
🇫🇷Nice, France
Centre Oscar Lambret
🇫🇷Lille, France
Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
🇫🇷Marseille, France
Centre Regional Rene Gauducheau
🇫🇷Nantes-Saint Herblain, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Centre Leon Berard
🇫🇷Lyon, France
Institut Curie Hopital
🇫🇷Paris, France
Centre Alexis Vautrin
🇫🇷Vandoeuvre-les-Nancy, France