Vaccine Therapy in Treating Patients With Stage IV Breast Cancer
|HER2-positive Breast Cancer Male Breast Cancer Recurrent Breast Cancer Stage IV Breast Cancer||Biological: HER-2/neu peptide vaccine Procedure: leukapheresis Biological: ex vivo-expanded HER2-specific T cells Drug: cyclophosphamide Biological: sargramostim Other: laboratory biomarker analysis||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Adoptive T Cell Therapy Following In Vivo Priming With a HER-2/Neu (HER2) Intracellular Domain (ICD) Peptide-Based Vaccine in Patients With Advanced Stage HER2 Overexpressing Breast Cancer|
- Evaluate Toxicity of Infusing HER2-specific T Cells as Assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 [ Time Frame: Up to 4 months after first booster vaccine ]Patients are monitored for the development of end organ damage by assessing adverse events with serum chemistries, liver function studies, complete blood counts, urine analysis and physical exams. All adverse events for all systems are graded on a scale of 1-5 and attribution is assigned. There are DLT criteria. DLT is defined as any incidence of Grade 3 hematologic and non-hematologic toxicity (excluding: fever, hypoxia, and urticaria) Thus, if a subject develops a Grade 3 toxicity (excluding those listed in Table 4) will be considered excessive toxicity and no further dose escalations will occur.
- Proportion of Patients Whose T Cells Persist at a Level the Same or Greater as the Level After the Final T Cell Infusion and Subsequent Booster Immunizations as Assessed by IFN-gamma (IFN-g) ELISPOT [ Time Frame: Up to 2 year following the last infusion ]
- Development of CD4+ and CD8+ Epitope Spreading [ Time Frame: Up to 2 years ]As assessed by the development of immunity to epitopes within the HER2 protein to which the patient was not vaccinated as well as the development of immunity to other breast cancer related tumor antigens.
- Response of Skeletal or Bone-only Disease by FDG-PET and According to European Organization for Research and Treatment for Cancer (EORTC) [ Time Frame: Up to 2 years ]
|Study Start Date:||October 2008|
|Study Completion Date:||December 2014|
|Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (vaccine therapy)
Patients receive HER2/neu peptide vaccine admixed with sargramostim (GM-CSF) ID on days 1, 8, and 15. Beginning 2 weeks later, patients undergo leukapheresis to isolate and collect peripheral blood mononuclear cells for T-cell expansion.
Patients receive cyclophosphamide IV once on day -1 and autologous ex vivo-expanded HER2-specific T cell IV over 30 minutes on day 1. Treatment repeats every 7-10 days for up to three immunizations. Patients receive a booster HER2/neu peptide vaccine 1 month after the final T-cell infusion, followed by 2 additional booster vaccines at 2-month intervals.
Biological: HER-2/neu peptide vaccine
Other Name: HER-2Procedure: leukapheresis
Undergo leukapheresisBiological: ex vivo-expanded HER2-specific T cells
Given IVDrug: cyclophosphamide
Other Names:Biological: sargramostim
Other Names:Other: laboratory biomarker analysis
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT00791037
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Mary Disis||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|