NCT00674414

Trastuzumab With or Without Everolimus in Treating Women With Breast Cancer That Can Be Removed By Surgery

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.

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 82 (actual)
• Sponsor: UNICANCER · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
BIOLOGICAL	trastuzumab	Trastuzumab (Herceptin®) IV once weekly
DRUG	everolimus	Oral everolimus once daily
PROCEDURE	therapeutic conventional surgery	Patients undergo surgery

Timeline

• Start date: 2008-04-01
• Primary completion: 2013-01-01
• First posted: 2008-05-07
• Last updated: 2013-01-18

Locations

8 sites across 1 country: France