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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

Phase 1/Phase 2
18 Years
Open (Enrolling)
HER2-positive Breast Cancer, Male Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer

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Trial Information

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


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.


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.


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

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

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.

Inclusion Criteria:

- Patients with HER2+ Stage IV breast cancer that have been maximally treated and not
achieved a complete remission

- Patients must have stable or slowly progressive disease state, measurable disease as:

- Extraskeletal disease that can be accurately measured >= 10 mm by standard
imaging techniques that can include but not limited to computed tomography (CT),
positron emission tomography (PET), PET/CT, magnetic resonance imaging (MRI);

- Skeletal or bone-only disease which is measurable by fludeoxyglucose (FDG) PET
or PET/CT imaging will also be allowed

- Patients can be currently receiving trastuzumab and/or lapatinib and/or hormonal
therapy and/or bisphosphonate therapy

- HER2 overexpression in the primary tumor or metastasis by immunohistochemistry (IHC)
of 2+ or 3+, or documented gene amplification by fluorescence in situ hybridization
(FISH) analysis; if overexpression is 2+ by IHC, then patients must have HER2 gene
amplification documented by FISH

- Subjects must have a Performance Status Score (Southwest Oncology Group [SWOG]/Zubrod
Scale) = 0, 1 or 2

- Patients must be off all immunosuppressive treatments such as chemotherapy or
systemic steroid therapy a minimum of 14 days prior to initiation of study (i.e.
first vaccination)

- Patients on trastuzumab and/or lapatinib must have a baseline left ventricular
ejection fraction (LVEF) measured by multi gated acquisition scan (MUGA) or
echocardiogram (ECHO) equal to or greater than the lower limit of normal for the
facility within 90 days of eligibility determination

- Men and women of reproductive ability must agree to contraceptive use during the
entire study period

- Patients must have an expected survival of 6 months

- White blood cell (WBC) >= 3000/mm^3

- Absolute neutrophil count (ANC) >= 1000/mm^3

- Hemoglobin (Hgb) >= 10 mg/dl

- Platelets >= 75,000/mm^3

- Serum creatinine =< 2.0 mg/dl or creatinine clearance > 60 ml/min

- Total bilirubin =< 2.5 mg/dl

- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) =< 3
times upper limit of normal (ULN)

- Patients must be >= 18 years old

Exclusion Criteria:

- Patients with any of the following cardiac conditions:

- Symptomatic restrictive cardiomyopathy;

- Unstable angina within 4 months prior to enrollment;

- New York Heart Association functional class III-IV heart failure on active

- Patients with any contraindication to receiving rhuGM-CSF based products

- Patients with any clinically significant autoimmune disease uncontrolled with

- Patients with a history of brain metastases must have a stable head imaging study
within 30 days of eligibility determination; specifically, patients with active brain
metastases will not be eligible for study

- Patients who are simultaneously enrolled in any other treatment study

- Pregnant or breast-feeding women

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety and systemic toxicity of infusing HER2-specific T cells as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0

Outcome Description:

Defined as safe if at least 75% of patients are able to receive all 3 infusions without dose-limiting toxicity (DLT), any incidence of Grade 3 hematologic and non-hematologic toxicity (excluding constitutional, pulmonary, or dermatology/skin categories) or any incidence of Grade 4 toxicity (excluding reversible Grade 4 blood/bone marrow category after cyclophosphamide).

Outcome Time Frame:

Up to 4 months after first booster vaccine

Safety Issue:


Principal Investigator

Mary Disis

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium


United States: Food and Drug Administration

Study ID:




Start Date:

October 2008

Completion Date:

Related Keywords:

  • HER2-positive Breast Cancer
  • Male Breast Cancer
  • Recurrent Breast Cancer
  • Stage IV Breast Cancer
  • Breast Neoplasms
  • Breast Neoplasms, Male



Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109