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Vaccine Therapy in Treating Patients With Stage IV Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00791037
Recruitment Status : Completed
First Posted : November 14, 2008
Results First Posted : May 25, 2017
Last Update Posted : May 25, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mary (Nora) Disis, University of Washington

Brief Summary:
This phase I/II trial is studying the side effects of escalating doses of adoptive T cell therapy in treating patients with stage IV breast cancer. Vaccines are given to patient prior the expansion of a person's white blood cells may help the body build an effective immune response to kill tumor cells that overexpress human epidermal growth factor receptor 2 (HER2)

Condition or disease Intervention/treatment Phase
HER2-positive Breast Cancer Male Breast Cancer Recurrent Breast Cancer Stage IV Breast Cancer Biological: HER-2/neu peptide vaccine Procedure: leukapheresis Biological: ex vivo-expanded HER2-specific T cells Drug: cyclophosphamide Biological: sargramostim Other: laboratory biomarker analysis Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : October 2008
Actual Primary Completion Date : July 2013
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Treatment (vaccine therapy)

Patients receive HER2/neu peptide vaccine admixed with sargramostim (GM-CSF) ID 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 once on day -1 and autologous ex vivo-expanded HER2-specific T cell IV over 30 minutes on day 1. Treatment repeats every 7-10 days for up to three immunizations. Patients receive a booster HER2/neu peptide vaccine 1 month after the final T-cell infusion, followed by 2 additional booster vaccines at 2-month intervals.

Biological: HER-2/neu peptide vaccine
Given ID
Other Name: HER-2

Procedure: leukapheresis
Undergo leukapheresis

Biological: ex vivo-expanded HER2-specific T cells
Given IV

Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana

Biological: sargramostim
Given ID
Other Names:
  • GM-CSF
  • Leukine
  • Prokine

Other: laboratory biomarker analysis
Correlative study

Primary Outcome Measures :
  1. Evaluate Toxicity of Infusing HER2-specific T Cells as Assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 [ Time Frame: Up to 4 months after first booster vaccine ]
    Patients are monitored for the development of end organ damage by assessing adverse events with serum chemistries, liver function studies, complete blood counts, urine analysis and physical exams. All adverse events for all systems are graded on a scale of 1-5 and attribution is assigned. There are DLT criteria. DLT is defined as any incidence of Grade 3 hematologic and non-hematologic toxicity (excluding: fever, hypoxia, and urticaria) Thus, if a subject develops a Grade 3 toxicity (excluding those listed in Table 4) will be considered excessive toxicity and no further dose escalations will occur.

Secondary Outcome Measures :
  1. Proportion of Patients Whose T Cells Persist at a Level the Same or Greater as the Level After the Final T Cell Infusion and Subsequent Booster Immunizations as Assessed by IFN-gamma (IFN-g) ELISPOT [ Time Frame: Up to 2 year following the last infusion ]
  2. Development of CD4+ and CD8+ Epitope Spreading [ Time Frame: Up to 2 years ]
    As assessed by the development of immunity to epitopes within the HER2 protein to which the patient was not vaccinated as well as the development of immunity to other breast cancer related tumor antigens.

  3. Response of Skeletal or Bone-only Disease by FDG-PET and According to European Organization for Research and Treatment for Cancer (EORTC) [ Time Frame: Up to 2 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients with HER2+ Stage IV breast cancer that have been maximally treated and not achieved a complete remission
  • Patients must have stable or slowly progressive disease state, measurable disease as:

    • Extraskeletal disease that can be accurately measured >= 10 mm by standard imaging techniques that can include but not limited to computed tomography (CT), positron emission tomography (PET), PET/CT, magnetic resonance imaging (MRI);
    • Skeletal or bone-only disease which is measurable by fludeoxyglucose (FDG) PET or PET/CT imaging will also be allowed
  • Patients can be currently receiving trastuzumab and/or lapatinib and/or hormonal therapy and/or bisphosphonate therapy
  • HER2 overexpression in the primary tumor or metastasis by immunohistochemistry (IHC) of 2+ or 3+, or documented gene amplification by fluorescence in situ hybridization (FISH) analysis; if overexpression is 2+ by IHC, then patients must have HER2 gene amplification documented by FISH
  • Subjects must have a Performance Status Score (Southwest Oncology Group [SWOG]/Zubrod Scale) = 0, 1 or 2
  • Patients must be off all immunosuppressive treatments such as chemotherapy or systemic steroid therapy a minimum of 14 days prior to initiation of study (i.e. first vaccination)
  • Patients on trastuzumab and/or lapatinib must have a baseline left ventricular ejection fraction (LVEF) measured by multi gated acquisition scan (MUGA) or echocardiogram (ECHO) equal to or greater than the lower limit of normal for the facility within 90 days of eligibility determination
  • Men and women of reproductive ability must agree to contraceptive use during the entire study period
  • Patients must have an expected survival of 6 months
  • White blood cell (WBC) >= 3000/mm^3
  • Absolute neutrophil count (ANC) >= 1000/mm^3
  • Hemoglobin (Hgb) >= 10 mg/dl
  • Platelets >= 75,000/mm^3
  • Serum creatinine =< 2.0 mg/dl or creatinine clearance > 60 ml/min
  • Total bilirubin =< 2.5 mg/dl
  • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) =< 3 times upper limit of normal (ULN)
  • Patients must be >= 18 years old

Exclusion Criteria:

  • Patients with any of the following cardiac conditions:

    • Symptomatic restrictive cardiomyopathy;
    • Unstable angina within 4 months prior to enrollment;
    • New York Heart Association functional class III-IV heart failure on active treatment
  • Patients with any contraindication to receiving rhuGM-CSF based products
  • Patients with any clinically significant autoimmune disease uncontrolled with treatment
  • Patients with a history of brain metastases must have a stable head imaging study within 30 days of eligibility determination; specifically, patients with active brain metastases will not be eligible for study
  • Patients who are simultaneously enrolled in any other treatment study
  • Pregnant or breast-feeding women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00791037

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United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
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Principal Investigator: Mary Disis Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Mary (Nora) Disis, Principal Investigator, University of Washington Identifier: NCT00791037    
Other Study ID Numbers: 6658
NCI-2009-01591 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
R01CA129517 ( U.S. NIH Grant/Contract )
First Posted: November 14, 2008    Key Record Dates
Results First Posted: May 25, 2017
Last Update Posted: May 25, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: We will report study data but will not call out individual participants.
Additional relevant MeSH terms:
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Breast Neoplasms
Breast Neoplasms, Male
Neoplasms by Site
Breast Diseases
Skin Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists