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

University of Washington

Status and phase: Withdrawn; Phase 1

Conditions: Male Breast Cancer; HER2-positive Breast Cancer; Stage IV Breast Cancer

Treatments: Other: laboratory biomarker analysis; Other: immunoenzyme technique; Drug: cyclophosphamide; Biological: HER-2/neu peptide vaccine; Other: flow cytometry; Biological: ex vivo-expanded HER2-specific T cells

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01219907

NCI-2010-01792

7266

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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0 participants in 1 patient group

Arm I

Experimental group

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.

Treatment:

Biological: ex vivo-expanded HER2-specific T cells

Biological: HER-2/neu peptide vaccine

Other: flow cytometry

Drug: cyclophosphamide

Other: immunoenzyme technique

Other: laboratory biomarker analysis