A Phase I Study of Infusion of HER-2/Neu Specific T Cells in Patients With Advanced Stage HER-2/Neu Expressing Cancers Who Have Received a HER-2/Neu Vaccine
18 Years
N/A
Both
HER2-positive Breast Cancer, Recurrent Breast Cancer, Recurrent Non-small Cell Lung Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Ovarian Germ Cell Tumor, Stage IV Breast Cancer, Stage IV Non-small Cell Lung Cancer, Stage IV Ovarian Epithelial Cancer, Stage IV Ovarian Germ Cell Tumor
Trial Information
A Phase I Study of Infusion of HER-2/Neu Specific T Cells in Patients With Advanced Stage HER-2/Neu Expressing Cancers Who Have Received a HER-2/Neu Vaccine
PRIMARY OBJECTIVES:
I. To assess the feasibility of expanding HER2 specific T cells ex vivo for infusion into
subjects who have advanced HER2 overexpressing cancer.
II. To assess the toxicity associated with infusing autologous HER2 specific T cells into
patients using either a single dose of cyclophosphamide or ONTAK (denileukin diftitox) prior
to T cell infusion.
SECONDARY OBJECTIVES:
I. To investigate to what extent HER2 specific T cell immunity can be boosted in individuals
treated with a single dose of cyclophosphamide of ONTAK followed by infusion of autologous
HER2 specific T cells.
II. To investigate the potential anti-tumor effects of HER2 specific T cells in patients
with HER2 overexpressing advanced-stage cancers.
III. To evaluate how long tumor antigen specific T cell immune augmentation persists in vivo
after a single dose of cyclophosphamide or ONTAK followed by infusion of autologous HER2
specific T cells.
OUTLINE: This is a dose-escalation study of ex vivo-expanded HER2-specific T cells. Patients
are assigned to 1 of 2 treatment groups.
GROUP A: Patients receive low-dose cyclophosphamide intravenously (IV) on day -1 and 3
escalating doses of autologous ex vivo-expanded HER2-specific T cells IV over 30 minutes on
days 1, 10, and 20.
GROUP B: Patients receive ONTAK (denileukin diftitox) IV over 1 hour on day -1 and 3
escalating doses of autologous ex vivo-expanded HER2-specific T cells IV over 30 minutes on
days 1, 10, and 20.
After completion of study treatment, patients are followed periodically.
Inclusion Criteria:
- Patients with progressive HER2/neu overexpressing metastatic breast, ovarian, or
non-small cell lung cancer not considered curable by conventional therapies,
including trastuzumab
- Extra-skeletal 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), magnetic resonance imaging (MRI)
- Skeletal or bone-only disease which is measurable by Fludeoxyglucose F 18 (FDG)
PET imaging will also be allowed
- Patients with ovarian cancer may have measurable disease; however, their only
indication of progression may be an abnormal CA-125
- Patients must have documented HER-2/neu overexpression in their tumor (either primary
or metastasis) as was required per the eligibility criteria of their original
vaccination protocol
- Patients must have received HER2-specific vaccinations while enrolled on a HER2
vaccine protocol approved at the University of Washington Human Subjects Division
- Patients must have undergone leukapheresis after vaccination through a protocol
approved at the University of Washington Human Subjects Division and have product
stored for clinical use
- Subjects must have a Performance Status Score (Zubrod/Eastern Cooperative Oncology
Group [ECOG] Scale) = 0 or 1
- Patients can be currently receiving trastuzumab and/or lapatinib and/or hormonal
therapy and/or bisphosphonate therapy
- Patients on trastuzumab and/or lapatinib must have adequate cardiac function as
demonstrated by multi gated acquisition (MUGA) scan or echocardiogram (ECHO)
within 90 days of eligibility determination
- Patients must be off all immunosuppressive treatments, and/or systemic steroid
therapy, for at least 14 days prior to initiation of study treatment
- Patients must be off chemotherapy and trastuzumab for at least 1 week prior to the
first infusion of T cells
- Men and women of reproductive ability must agree to contraceptive use during the
study and for one month after the final T cell infusion
- Patients with a history of brain metastases must have a stable head imaging study
within 30 days of enrollment
- White blood cells (WBC) >= 3000/mm^3
- Absolute neutrophil count (ANC) >= 1000/mm^3
- Hemoglobin (Hgb) >= 10 mg/dl
- Platelets >= 75,000mm^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 ULN
Exclusion Criteria:
- Concurrent enrollment in other treatment studies
- Patients with any of the following cardiac conditions:
- Symptomatic restrictive cardiomyopathy
- Unstable angina within the last 4 months prior to enrollment
- New York Heart Association functional class III-IV heart failure on active
treatment
- Patients with any clinically significant autoimmune disease uncontrolled with
treatment
- Pregnant or breast-feeding women
- Known history of hypersensitivity to diphtheria toxin or interleukin (IL)-2 (only for
subjects enrolled in Group B)
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Feasibility of expanding HER2 specific T cells ex vivo to achieve a target T cell expansion of 1x10^10 HER2 specific T cells
Outcome Description:
The procedure will be defined as feasible if the minimum target expansion of HER2 specific T cells is achieved in 2/3 expansions in 4/5 subjects within an arm.
Outcome Time Frame:
Up to day 40
Safety Issue:
No
Principal Investigator
Mary Disis
Investigator Role:
Principal Investigator
Investigator Affiliation:
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Authority:
United States: Food and Drug Administration
Study ID:
6223
NCT ID:
NCT00228358
Start Date:
June 2003
Completion Date:
Related Keywords:
- HER2-positive Breast Cancer
- Recurrent Breast Cancer
- Recurrent Non-Small Cell Lung Cancer
- Recurrent Ovarian Epithelial Cancer
- Recurrent Ovarian Germ Cell Tumor
- Stage IV Breast Cancer
- Stage IV Non-Small Cell Lung Cancer
- Stage IV Ovarian Epithelial Cancer
- Stage IV Ovarian Germ Cell Tumor
- Breast Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Lung Neoplasms
- Neoplasms, Germ Cell and Embryonal
- Germinoma
- Ovarian Neoplasms
- Neoplasms, Glandular and Epithelial
Name | Location |
|---|---|
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle, Washington 98109 |
