Ex Vivo-Expanded HER2-Specific T Cells and Cyclophosphamide After Vaccine Therapy in Treating Patients With HER2-Positive Stage IV Breast Cancer

NCT ID: NCT01219907

Last Updated: 2013-05-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2012-06-30

Brief Summary

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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

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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.

Conditions

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HER2-positive Breast Cancer Male Breast Cancer Stage IV Breast Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm I

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.

Group Type EXPERIMENTAL

HER-2/neu peptide vaccine

Intervention Type BIOLOGICAL

Given intradermally

cyclophosphamide

Intervention Type DRUG

Given IV

ex vivo-expanded HER2-specific T cells

Intervention Type BIOLOGICAL

Given IV

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

flow cytometry

Intervention Type OTHER

Correlative studies

immunoenzyme technique

Intervention Type OTHER

Correlative studies

Interventions

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HER-2/neu peptide vaccine

Given intradermally

Intervention Type BIOLOGICAL

cyclophosphamide

Given IV

Intervention Type DRUG

ex vivo-expanded HER2-specific T cells

Given IV

Intervention Type BIOLOGICAL

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

flow cytometry

Correlative studies

Intervention Type OTHER

immunoenzyme technique

Correlative studies

Intervention Type OTHER

Other Intervention Names

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HER-2 CPM CTX Cytoxan Endoxan Endoxana Enduxan immunoenzyme techniques

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role lead

Responsible Party

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Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Principal Investigators

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Lupe Salazar

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Locations

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Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2010-01792

Identifier Type: -

Identifier Source: secondary_id

7266

Identifier Type: -

Identifier Source: org_study_id

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