Ex Vivo-Expanded HER2-Specific T Cells and Cyclophosphamide After Vaccine Therapy in Treating Patients With HER2-Positive Stage IV Breast Cancer
Primary Purpose
HER2-positive Breast Cancer, Male Breast Cancer, Stage IV Breast Cancer
Status
Withdrawn
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
HER-2/neu peptide vaccine
cyclophosphamide
ex vivo-expanded HER2-specific T cells
laboratory biomarker analysis
flow cytometry
immunoenzyme technique
Sponsored by
About this trial
This is an interventional treatment trial for HER2-positive Breast Cancer
Eligibility Criteria
Inclusion Criteria:
- Patients with HER-2+ Stage IV breast cancer that have been maximally treated and not in a complete remission
- Subjects must be > 18 years old
- Extra skeletal disease that can be accurately measured in at least one dimension as >= 20 mm with conventional CT techniques or >= 10 mm with spiral CT scan
- Skeletal or bone-only disease that is measurable by FDG PET imaging will also be allowed
- Patients can be receiving trastuzumab and/or hormonal therapy and/or bisphosphonates
- HER2 overexpression in the primary tumor or metastasis by IHC of 2+ or 3+, or documented gene amplification by FISH analysis; if over expression is 2+ by IHC, patients must have HER2 gene amplification documented by FISH
- Performance Status Score (ECOG/Zubrod Scale) must be =< 2
- Patients must be off all immunosuppressive treatments such as chemotherapy or systemic steroid therapy a minimum of 3 weeks prior to initiation of study (i.e. first vaccination)
- Patients on trastuzumab must have a baseline LVEF measured by MUGA or echocardiogram >= the lower limit of normal for the facility within 3 months of enrollment to study
- Subjects must be HLA-A2 (HLA A*0201) positive
- ANC >= 1000/mm^3
- Hgb >= 10 mg/dl
- Platelet count >= 75,000/mm^3
- Men and women of reproductive ability must agree to use contraceptives during the entire study period
Exclusion Criteria:
- Serum creatinine > 2.0 mg/dl
- Serum bilirubin > 2.5 times the upper limit of normal
- Contraindication to receiving GM-CSF based vaccine products
- New York Heart Association functional class III-IV heart failure, symptomatic pericardial effusion, or unstable angina
- History of disorders associated with immunosuppression such as HIV
- Pregnant or breast-feeding women
- ANC < 1000/mm^3
- Hgb < 10 mg/dl
- Platelet count < 75,000/mm^3
- Active brain metastasis
Sites / Locations
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Arm I
Arm Description
VACCINE THERAPY: Patients receive HER2 peptide vaccine intradermally once weekly for 3 weeks. CHEMOTHERAPY: Patients receive cyclophosphamide IV on day -1. IMMUNOTHERAPY: Patients receive ex vivo-expanded HER2 specific T-cell IV over 30 minutes on days 1, 10, and 20.
Outcomes
Primary Outcome Measures
Ability to expand HER-2-specific T cells ex vivo from memory T cell subsets which are derived from patients with advanced HER-2 expressing cancer
Ability to expand HER-2-specific T cells ex vivo from memory T cell subsets which are derived from patients with advanced HER-2 expressing cancer will be defined as feasible if the minimum target expansion of HER-2-specific T cells is achieved in ≥2/3 expansions in ≥7/10 subjects.
Safety and systemic toxicity as assessed at regular time points by NCI common toxicity criteria (CTCAE v 4.0). Stopping rules for the study protect patients against therapy with a rate of severe toxicity of 20% or greater.
Secondary Outcome Measures
Extent to which to HER-2-specific T cell immunity can be boosted successfully with adoptive immunotherapy will be defined by quantitative assessment of HER-2-specific CD8+ T cells assessed by cytokine flow cytometry (CFC), Elispot, and tetramer staining
Persistence of T cell immune augmentation in vivo after adoptive transfer of HER-2-specific T cells as assessed by presence of HER-2-specific central memory T cells and effector memory T cells
Anti-tumor effects of HER-2-specific T cells as assessed by RECIST criteria
Full Information
NCT ID
NCT01219907
First Posted
September 22, 2010
Last Updated
May 15, 2013
Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT01219907
Brief Title
Ex Vivo-Expanded HER2-Specific T Cells and Cyclophosphamide After Vaccine Therapy in Treating Patients With HER2-Positive Stage IV Breast Cancer
Official Title
Phase I Study of Adoptive T-Cell Therapy With HER-2/Neu (HER-2)-Specific Memory CD8+ T Lymphocytes Obtained Following In Vivo Priming With a Peptide Vaccine in Patients With Advanced Stage HER-2-Positive Breast Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
May 2013
Overall Recruitment Status
Withdrawn
Study Start Date
June 2012 (undefined)
Primary Completion Date
June 2014 (Anticipated)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
RATIONALE : Laboratory-treated T cells may stimulate the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vaccines made from HER2 peptides may help the body build an effective immune response to kill tumor cells that express HER2. Giving laboratory-treated T cells and cyclophosphamide after vaccine therapy may be an effective treatment for breast cancer.
PURPOSE: This phase I trial is studying the side effects and best dose of ex vivo-expanded HER2-specific T cells when given together with cyclophosphamide after vaccine therapy in treating patients with HER2-positive stage IV breast cancer.
Detailed Description
PRIMARY OBJECTIVES:
I. To evaluate the feasibility of expanding HER-2-specific effector T cells (TE) ex vivo from CD62L+ TCM and CD62L- TEM from patients immunized with a HER-2 peptide vaccine.
II. To evaluate the safety of infusing autologous ex vivo expanded HER-2-specific T cells into patients with advanced HER-2+ breast cancer.
SECONDARY OBJECTIVES:
I. To evaluate the persistence, function, and phenotype of adoptively transferred HER-2-specific TE cells derived from TCM or TEM precursors.
II. To investigate the potential anti-tumor effects of therapy with ex vivo expanded HER-2-specific T cells in patients with advanced HER-2+ breast cancer.
OUTLINE : This is a dose-escalation study of ex vivo-expanded HER2-specific T cells.
VACCINE THERAPY: Patients receive HER2 peptide vaccine intradermally once weekly for 3 weeks.
CHEMOTHERAPY: Patients receive cyclophosphamide IV on day -1.
IMMUNOTHERAPY: Patients receive ex vivo-expanded HER2 specific T-cell IV over 30 minutes on days 1, 10, and 20.
After completion of study treatment, patients are followed up on days 28, 35, 49, 63 and then monthly thereafter for 1 year.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HER2-positive Breast Cancer, Male Breast Cancer, Stage IV Breast Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm I
Arm Type
Experimental
Arm Description
VACCINE THERAPY: Patients receive HER2 peptide vaccine intradermally once weekly for 3 weeks.
CHEMOTHERAPY: Patients receive cyclophosphamide IV on day -1.
IMMUNOTHERAPY: Patients receive ex vivo-expanded HER2 specific T-cell IV over 30 minutes on days 1, 10, and 20.
Intervention Type
Biological
Intervention Name(s)
HER-2/neu peptide vaccine
Other Intervention Name(s)
HER-2
Intervention Description
Given intradermally
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
CPM, CTX, Cytoxan, Endoxan, Endoxana, Enduxan
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
ex vivo-expanded HER2-specific T cells
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
flow cytometry
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
immunoenzyme technique
Other Intervention Name(s)
immunoenzyme techniques
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Ability to expand HER-2-specific T cells ex vivo from memory T cell subsets which are derived from patients with advanced HER-2 expressing cancer
Description
Ability to expand HER-2-specific T cells ex vivo from memory T cell subsets which are derived from patients with advanced HER-2 expressing cancer will be defined as feasible if the minimum target expansion of HER-2-specific T cells is achieved in ≥2/3 expansions in ≥7/10 subjects.
Time Frame
After leukapheresis (2 weeks after 3rd vaccination) and prior to chemotherapy
Title
Safety and systemic toxicity as assessed at regular time points by NCI common toxicity criteria (CTCAE v 4.0). Stopping rules for the study protect patients against therapy with a rate of severe toxicity of 20% or greater.
Time Frame
At week 1, 2, 3, post T-Cell infusion day 1, 10, 20, 28, 35, 49, 63, then every 3 months for a year.
Secondary Outcome Measure Information:
Title
Extent to which to HER-2-specific T cell immunity can be boosted successfully with adoptive immunotherapy will be defined by quantitative assessment of HER-2-specific CD8+ T cells assessed by cytokine flow cytometry (CFC), Elispot, and tetramer staining
Time Frame
Post T-Cell-infusion on day 10, 20, 28, 35, 49, 63, then monthly for one year.
Title
Persistence of T cell immune augmentation in vivo after adoptive transfer of HER-2-specific T cells as assessed by presence of HER-2-specific central memory T cells and effector memory T cells
Time Frame
Every month for 1 year following the last infusion
Title
Anti-tumor effects of HER-2-specific T cells as assessed by RECIST criteria
Time Frame
Day 63 post transplant
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with HER-2+ Stage IV breast cancer that have been maximally treated and not in a complete remission
Subjects must be > 18 years old
Extra skeletal disease that can be accurately measured in at least one dimension as >= 20 mm with conventional CT techniques or >= 10 mm with spiral CT scan
Skeletal or bone-only disease that is measurable by FDG PET imaging will also be allowed
Patients can be receiving trastuzumab and/or hormonal therapy and/or bisphosphonates
HER2 overexpression in the primary tumor or metastasis by IHC of 2+ or 3+, or documented gene amplification by FISH analysis; if over expression is 2+ by IHC, patients must have HER2 gene amplification documented by FISH
Performance Status Score (ECOG/Zubrod Scale) must be =< 2
Patients must be off all immunosuppressive treatments such as chemotherapy or systemic steroid therapy a minimum of 3 weeks prior to initiation of study (i.e. first vaccination)
Patients on trastuzumab must have a baseline LVEF measured by MUGA or echocardiogram >= the lower limit of normal for the facility within 3 months of enrollment to study
Subjects must be HLA-A2 (HLA A*0201) positive
ANC >= 1000/mm^3
Hgb >= 10 mg/dl
Platelet count >= 75,000/mm^3
Men and women of reproductive ability must agree to use contraceptives during the entire study period
Exclusion Criteria:
Serum creatinine > 2.0 mg/dl
Serum bilirubin > 2.5 times the upper limit of normal
Contraindication to receiving GM-CSF based vaccine products
New York Heart Association functional class III-IV heart failure, symptomatic pericardial effusion, or unstable angina
History of disorders associated with immunosuppression such as HIV
Pregnant or breast-feeding women
ANC < 1000/mm^3
Hgb < 10 mg/dl
Platelet count < 75,000/mm^3
Active brain metastasis
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lupe Salazar
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Ex Vivo-Expanded HER2-Specific T Cells and Cyclophosphamide After Vaccine Therapy in Treating Patients With HER2-Positive Stage IV Breast Cancer
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