Vaccine Therapy in Treating Patients With Stage IV Breast Cancer - Full Text View

Sponsors and Collaborators:	Fred Hutchinson Cancer Research Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00791037

Purpose

RATIONALE: Vaccines made from a person's white blood cells may help the body build an effective immune response to kill tumor cells that overexpress HER2.

PURPOSE: This phase I/II trial is studying the side effects and best dose of vaccine therapy in treating patients with stage IV breast cancer.

Condition	Intervention	Phase
Breast Cancer	Biological: HER-2/neu peptide vaccine Biological: ex vivo-expanded HER2-specific T cells Biological: sargramostim Biological: trastuzumab Drug: cyclophosphamide Genetic: gene expression analysis Genetic: polymerase chain reaction Other: flow cytometry Other: immunoenzyme technique Other: laboratory biomarker analysis Procedure: leukapheresis	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized
Official Title:	Phase I/II Study of Adoptive T Cell Therapy Following In Vivo Priming With a HER-2/Neu (HER2) Intracellular Domain (ICD) Peptide-Based Vaccine in Patients With Advanced Stage HER2 Overexpressing Breast Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Cyclophosphamide Sargramostim Trastuzumab

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Safety of infusing HER2-specific T cells [ Designated as safety issue: Yes ]
Systemic toxicity according to NCI CTCAE v3.0 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

T-cell immunity [ Designated as safety issue: No ]
Anti-tumor effect after T-cell infusion [ Designated as safety issue: No ]
Response according to RECIST [ Designated as safety issue: No ]
Response of skeletal or bone-only disease according to European Organization for Research and Treatment for Cancer (EORTC) [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	October 2008
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

To evaluate the safety of infusing escalating doses of HER2-specific T cells into patients with stage IV HER2-positive (HER2+) breast cancer using ex vivo expanded autologous T cells.

Secondary

To investigate to what extent HER2-specific T-cell immunity can be boosted or generated in individuals after infusion of HER2-specific T cells.
To evaluate how long T-cell immune augmentation persists in vivo after adoptive transfer of HER2-specific T cells and subsequent booster immunizations in these patients.
To determine the development of CD4-positive and CD8-positive epitope spreading after adoptive transfer of HER2-specific T cells in these patients.

Tertiary

To investigate the potential anti-tumor effects of HER2-specific T cells in these patients.

OUTLINE: This is a dose-escalation study of ex vivo-expanded HER2-specific autologous T cells.

Patients receive HER-2/neu peptide vaccine admixed with sargramostim (GM-CSF) intradermally on days 1, 8, and 15.

Beginning 2 weeks later, patients undergo leukapheresis to isolate and collect peripheral blood mononuclear cells for T-cell expansion.

Patients receive cyclophosphamide IV on day -1 and autologous ex vivo-expanded HER2-specific T cells IV over 30 minutes on day 1. Treatment repeats every 7-10 days for a total of three immunizations. Patients receive a booster vaccine 1 month after the final T-cell infusion, followed by 2 additional booster vaccines at 2-month intervals.

Patients may continue trastuzumab (Herceptin®) IV weekly or every 3 weeks, except for 7 days before the cyclophosphamide dose.

Blood samples are obtained at baseline and then periodically during and after treatment. T-cell responses are analyzed periodically utilizing ELISPOT and cytokine flow cytometry, FOXP3 gene expression is assessed by PCR, and cytokine and chemokine levels are measured.

After completion of study therapy, patients are followed every 3 months for 1 year and then every 4 months for 1 year. Continued analysis for T-cell persistence is offered to the patients twice a year thereafter.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of breast cancer
- Stage IV disease
- Previously treated disease
  - Maximally treated and has not achieved a complete remission
Not considered curable by conventional therapies
HER2 overexpression in the primary tumor or metastasis diagnosed by IHC of 2^+ or 3^+, or documented gene amplification by FISH analysis; if overexpression is 2^+ by IHC, then patients must have HER2 gene amplification documented by FISH
Stable or slowly progressive disease
Measurable disease, defined as stable disease, while receiving trastuzumab (Herceptin®) and/or hormonal therapy or bisphosphonates
- Extraskeletal disease accurately measured in ≥ 1 dimension as ≥ 20 mm with conventional CT techniques or ≥ 10 mm with spiral CT scan
- Skeletal or bone-only disease measurable by fludeoxyglucose F 18 positron emission tomography
History of brain metastases must have a stable head imaging study within 30 days of enrollment
- Active brain metastases are not eligible
Hormone receptor status not specified

PATIENT CHARACTERISTICS:

SWOG/Zubrod performance status 0-2
Menopausal status not specified
Life expectancy ≥ 6 months
Not pregnant or nursing
Fertile patients must use effective contraception
ANC ≥ 1,000/mm³
Hemoglobin ≥ 10 mg/dL
Platelet count ≥ 100,000/mm³
Serum creatinine ≤ 2.0 mg/dL
Serum bilirubin ≤ 2.5 times upper limit of normal
No contraindication to receive granulocyte-macrophage colony-stimulating factor-based vaccine products
No history of disorders associated with immunosuppression (e.g., HIV)
No NYHA class III-IV heart failure
No symptomatic pericardial effusion
No unstable angina
Must have a baseline LVEF measured by MUGA or ECHO ≥ lower limit of normal (if on trastuzumab and/or lapatinib) within the past 6 months

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
At least 3 weeks since prior immunosuppressive treatments (e.g., chemotherapy or systemic steroid therapy)
Concurrent trastuzumab and/or lapatinib, hormonal therapy, and/or bisphosphonates allowed
- At least 7 days since prior chemotherapy and trastuzumab and/or lapatinib before cyclophosphamide administration
No concurrent enrollment in other treatment studies

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00791037

Locations

United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Recruiting
Seattle, Washington, United States, 98109-1024
Contact: Clinical Trials Office - Fred Hutchinson Cancer Research Cente 800-804-8824

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Mary (Nora) L. Disis, MD

University of Washington

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	University Cancer Center at University of Washington Medical Center ( Mary (Nora) L. Disis )
Study ID Numbers:	CDR0000618560, UWCC-6658, IR-6658
Study First Received:	November 13, 2008
Last Updated:	July 3, 2009
ClinicalTrials.gov Identifier:	NCT00791037 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

male breast cancer
recurrent breast cancer
stage IV breast cancer
HER2-positive breast cancer

Study placed in the following topic categories:

Skin Diseases
Immunologic Factors
Breast Neoplasms
Breast Cancer, Male
Cyclophosphamide
Immunosuppressive Agents
Recurrence

Breast Neoplasms, Male
Trastuzumab
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents
Breast Diseases

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Skin Diseases
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Breast Neoplasms
Cyclophosphamide
Immunosuppressive Agents
Pharmacologic Actions

Neoplasms
Neoplasms by Site
Therapeutic Uses
Myeloablative Agonists
Trastuzumab
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents
Breast Diseases

ClinicalTrials.gov processed this record on September 10, 2009