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Vaccine Therapy in Treating Patients With Stage IV Breast Cancer

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ClinicalTrials.gov Identifier: NCT00791037
Recruitment Status : Completed
First Posted : November 14, 2008
Results First Posted : May 25, 2017
Last Update Posted : May 25, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mary (Nora) Disis, University of Washington

Tracking Information
First Submitted Date  ICMJE November 13, 2008
First Posted Date  ICMJE November 14, 2008
Results First Submitted Date  ICMJE October 13, 2016
Results First Posted Date  ICMJE May 25, 2017
Last Update Posted Date May 25, 2017
Study Start Date  ICMJE October 2008
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 17, 2017)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 13, 2008)
  • Safety of infusing HER2-specific T cells
  • Systemic toxicity according to NCI CTCAE v3.0
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 5, 2013)
  • 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 ]
  • 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.
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 13, 2008)
  • T-cell immunity
  • Anti-tumor effect after T-cell infusion
  • Response according to RECIST
  • Response of skeletal or bone-only disease according to European Organization for Research and Treatment for Cancer (EORTC)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vaccine Therapy in Treating Patients With Stage IV Breast Cancer
Official Title  ICMJE 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
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)
Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the safety of infusing escalating doses of HER2 specific T cells into patients with advanced HER2+ breast cancer using ex vivo expanded autologous T cells.

SECONDARY OBJECTIVES:

I. To investigate to what extent HER2 specific T cell immunity can be boosted or generated in individuals after infusion of HER2 specific T cells.

II. To evaluate how long T cell immune augmentation persists in vivo after adoptive transfer of HER2 specific T cells and subsequent booster immunizations.

III. To determine the development of cluster of differentiation (CD)4+ and CD8+ epitope spreading after adoptive transfer of HER2 specific T cells.

TERTIARY OBJECTIVES:

I. To investigate the potential anti-tumor effects of HER2 specific T cells in patients with advanced HER2+ breast cancer.

II. To determine whether indium-labeled HER-2 specific T-cells traffic to sites of metastatic disease once adoptively transferred using SPECT or SPECT-CT imaging.

III. To assess whether adoptively transferred HER-2 specific T-cells induce acute inflammation at metastatic sites of disease by assessing the development of tumor inflammation after the second or third infusion of cells using PET-CT imaging.

OUTLINE: This is a phase I/II, dose-escalation study of ex vivo-expanded HER2-specific autologous T cells.

Patients receive HER2/neu peptide vaccine admixed with sargramostim (GM-CSF) intradermally (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 intravenously (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 treatments. 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.

While on the study, patients may continue their standard-of-care (non-research) treatment with trastuzumab and/or lapatinib IV weekly or every 3 weeks, except for 7 days before the cyclophosphamide dose, treatment 1 and treatment 2 and at least 7 days after receiving the second T cell vaccine. (Trastuzumab and lapatinib are not required or provided in this study).

Before the third T cell treatment of HER2 specific T-cells we will label a small sample of the patient's T-cells with indium-111. Prior to the final infusion of T-cells, patients will have FDG PET-CT performed. This scan will be repeated 48 hours after T-cell infusion. In addition, patients would then undergo SPECT or SPECT-CT imaging at 4, 24, 48, and 72 hours (+/- 3 hours) after labeled cells have been infused.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for the following year, and then twice a year thereafter. This consists of blood collection and contact with patients physician.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • HER2-positive Breast Cancer
  • Male Breast Cancer
  • Recurrent Breast Cancer
  • Stage IV Breast Cancer
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.

Interventions:
  • Biological: HER-2/neu peptide vaccine
  • Procedure: leukapheresis
  • Biological: ex vivo-expanded HER2-specific T cells
  • Drug: cyclophosphamide
  • Biological: sargramostim
  • Other: laboratory biomarker analysis
Publications * Stanton SE, Eary JF, Marzbani EA, Mankoff D, Salazar LG, Higgins D, Childs J, Reichow J, Dang Y, Disis ML. Concurrent SPECT/PET-CT imaging as a method for tracking adoptively transferred T-cells in vivo. J Immunother Cancer. 2016 May 17;4:27. doi: 10.1186/s40425-016-0131-3. eCollection 2016.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 17, 2017)
23
Original Estimated Enrollment  ICMJE
 (submitted: November 13, 2008)
20
Actual Study Completion Date  ICMJE December 2014
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00791037
Other Study ID Numbers  ICMJE 6658
NCI-2009-01591 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
R01CA129517 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: We will report study data but will not call out individual participants.
Responsible Party Mary (Nora) Disis, University of Washington
Study Sponsor  ICMJE University of Washington
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Mary Disis Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
PRS Account University of Washington
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP