Clinical trial NCT00791037
Conditions: HER2-positive Breast Cancer Male Breast Cancer Recurrent Breast Cancer Stage IV Breast Cancer
Sponsor: University of Washington
Start date: 2008-10-01; Completion date: 2014-12-01
Enrollment: 23 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase I/II trial is studying the side effects of escalating doses of adoptive T cell therapy in treating patients with stage IV breast cancer. Vaccines are given to patient prior the expansion of a person's white blood cells may help the body build an effective immune response to kill tumor cells that overexpress human epidermal growth factor receptor 2 (HER2)

Detailed description:
PRIMARY OBJECTIVES:

I. To evaluate the safety of infusing escalating doses of HER2 specific T cells into patients with advanced HER2+ breast cancer using ex vivo expanded autologous T cells.

SECONDARY OBJECTIVES:

I. To investigate to what extent HER2 specific T cell immunity can be boosted or generated in individuals after infusion of HER2 specific T cells.

II. To evaluate how long T cell immune augmentation persists in vivo after adoptive transfer of HER2 specific T cells and subsequent booster immunizations.

III. To determine the development of cluster of differentiation (CD)4+ and CD8+ epitope spreading after adoptive transfer of HER2 specific T cells.

TERTIARY OBJECTIVES:

I. To investigate the potential anti-tumor effects of HER2 specific T cells in patients with advanced HER2+ breast cancer.

II. To determine whether indium-labeled HER-2 specific T-cells traffic to sites of metastatic disease once adoptively transferred using SPECT or SPECT-CT imaging.

III. To assess whether adoptively transferred HER-2 specific T-cells induce acute inflammation at metastatic sites of disease by assessing the development of tumor inflammation after the second or third infusion of cells using PET-CT imaging.

OUTLINE: This is a phase I/II, dose-escalation study of ex vivo-expanded HER2-specific autologous T cells.

Patients receive HER2/neu peptide vaccine admixed with sargramostim (GM-CSF) intradermally (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 intravenously (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 treatments. 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.

While on the study, patients may continue their standard-of-care (non-research) treatment with trastuzumab and/or lapatinib IV weekly or every 3 weeks, except for 7 days before the cyclophosphamide dose, treatment 1 and treatment 2 and at least 7 days after receiving the second T cell vaccine. (Trastuzumab and lapatinib are not required or provided in this study).

Before the third T cell treatment of HER2 specific T-cells we will label a small sample of the patient's T-cells with indium-111. Prior to the final infusion of T-cells, patients will have FDG PET-CT performed. This scan will be repeated 48 hours after T-cell infusion. In addition, patients would then undergo SPECT or SPECT-CT imaging at 4, 24, 48, and 72 hours (+/- 3 hours) after labeled cells have been infused.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for the following year, and then twice a year thereafter. This consists of blood collection and contact with patients physician.

Arms: arm 1: 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.
Interventions: intervention 1: HER-2/neu peptide vaccine intervention 2: leukapheresis intervention 3: ex vivo-expanded HER2-specific T cells intervention 4: cyclophosphamide intervention 5: sargramostim intervention 6: laboratory biomarker analysis
Intervention descriptions: intervention 1: Given ID intervention 2: Undergo leukapheresis intervention 3: Given IV intervention 4: Given IV intervention 5: Given ID intervention 6: Correlative study

Protocol documents: