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

NCT01219907 | Withdrawn Phase 1

• 2 other identifiers: 7266NCI-2010-01792
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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.

  After leukapheresis (2 weeks after 3rd vaccination) and prior to chemotherapy

• 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.

  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 Outcomes (3)

• 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

  Post T-Cell-infusion on day 10, 20, 28, 35, 49, 63, then monthly for one year.

• 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

  Every month for 1 year following the last infusion

• Anti-tumor effects of HER-2-specific T cells as assessed by RECIST criteria

  Day 63 post transplant

Study Arms (1)

Arm I

EXPERIMENTAL

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.

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

Interventions

HER-2/neu peptide vaccine BIOLOGICAL

Given intradermally

Also known as: HER-2

Arm I

cyclophosphamide DRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana, Enduxan

Arm I

ex vivo-expanded HER2-specific T cells BIOLOGICAL

Given IV

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

flow cytometry OTHER

Correlative studies

Arm I

immunoenzyme technique OTHER

Correlative studies

Also known as: immunoenzyme techniques

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Breast Neoplasms, Male; Breast Neoplasms

Interventions

Cyclophosphamide; Flow Cytometry; Immunoenzyme Techniques

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Investigative Techniques; Immunoassay; Immunologic Techniques; Immunohistochemistry; Molecular Probe Techniques

Study Officials

• Lupe Salazar

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 22, 2010
• First Posted: October 13, 2010
• Study Start: June 1, 2012
• Primary Completion: June 1, 2014
• Last Updated: May 17, 2013

Record last verified: 2013-05

Locations

US (1)