Clinical Trials /

Immune Response and Potential Booster for Patients Who Have Received HER2-pulsed DC1

NCT03630809

Description:

The purpose of this study is to learn more about how to treat patients with a diagnosis of diagnosis of Human Epidermal Growth Factor Receptor 2/neu (HER-2/neu) positive breast cancer in the past, who were previously treated with HER-2/neu-directed dendritic cells (DC) vaccines. There is evidence that the use of anti-HER2 dendritic cell (DC) study vaccines could improve response to breast cancer therapy and be an important step in the prevention of recurrence. This study will use a Dendritic Cell Type 1 (DC1) vaccine which is a HER2-sensitized dendritic cell (DC) study vaccine. Dendritic cells are immune cells that can tell the participant's immune system to fight infection. This study vaccine will be made from the participant's blood cells collected from a procedure called leukapheresis.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Immune Response and Potential Booster for Patients Who Have Received HER2-pulsed DC1
  • Official Title: Immune Response Surveillance and Potential Booster Vaccines for Patients Who Have Received HER2-pulsed DC1 Vaccine

Clinical Trial IDs

  • ORG STUDY ID: MCC-19650
  • NCT ID: NCT03630809

Conditions

  • Breast Cancer
  • HER2-positive Breast Cancer
  • HER-2 Gene Amplification
  • HER2 Positive Breast Carcinoma
  • HER-2 Protein Overexpression
  • Breast Cancer, Male
  • Breast Cancer Female

Interventions

DrugSynonymsArms
HER2 DC1 VaccineVaccineHER2 DC1 Vaccine

Purpose

The purpose of this study is to learn more about how to treat patients with a diagnosis of diagnosis of Human Epidermal Growth Factor Receptor 2/neu (HER-2/neu) positive breast cancer in the past, who were previously treated with HER-2/neu-directed dendritic cells (DC) vaccines. There is evidence that the use of anti-HER2 dendritic cell (DC) study vaccines could improve response to breast cancer therapy and be an important step in the prevention of recurrence. This study will use a Dendritic Cell Type 1 (DC1) vaccine which is a HER2-sensitized dendritic cell (DC) study vaccine. Dendritic cells are immune cells that can tell the participant's immune system to fight infection. This study vaccine will be made from the participant's blood cells collected from a procedure called leukapheresis.

Trial Arms

NameTypeDescriptionInterventions
HER2 DC1 VaccineExperimentalHER2 DC1 vaccine given in 3 booster injections administered every 3 months for the treatment of participants with nonmetastatic HER2pos breast cancer (BC) with low HER2 immunity and history of prior treatment with HER2 DC1 vaccines.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Patients with a diagnosis of nonmetastatic classic HER2pos (ie, IHC 3+ or FISHpos)
                 breast cancer (BC) who have previously been vaccinated with DC1 HER2-pulsed vaccines
                 on any of several prior clinical trials for ductal carcinoma in situ (DCIS) or
                 inflammatory breast cancer (IBC) are eligible; however, we also allowed HER2 2+
                 patients in many of these prior trials and they will also be allowed to participate in
                 this trial. Note: HER2pos BC is defined by tumor tissue HER2 overexpression and or
                 tumor HER2 amplification. The lack of HER2 overexpression by IHC is defined as 0 or 1+
                 whereas overexpression is defined as 3+. In the event of equivocal IHC, 2+, the tumor
                 must be gene-amplified by fluorescent in situ hybridization (FISH) performed upon the
                 primary tumor or metastatic lesion (ratio > 2 and HER2 copy number > 4 define
                 HER2negdisease).
    
              -  Participants must have completed all standard-of-care treatment for nonmetastatic BC
                 (e.g., surgery, chemotherapy, radiation therapy, and HER2-targeted therapy). Note:
                 antiestrogen therapy is permitted while on trial.
    
              -  Age ≥ 18 years.
    
              -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
    
              -  Participants must have normal organ and marrow function within 2 weeks of
                 registration.
    
              -  Left ventricular ejection fraction above institutional lower limit of normal (by
                 echocardiogram or multigated acquisition (MUGA) scan within 6 months of registration).
    
              -  For both male and female patients, effective methods of contraception must be used
                 throughout the study and for 3 months following the last dose.
    
              -  Must have the ability to understand and the willingness to sign a written informed
                 consent prior to registration on study.
    
            Exclusion Criteria:
    
              -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
                 infection, congenital prolonged QT syndrome, symptomatic congestive heart failure,
                 unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations
                 that would limit compliance with study requirements.
    
              -  Current use of immunosuppressive agents or systemic corticosteroids. Topical, ocular,
                 intra-articular, intranasal, inhalational corticosteroids (with minimal systemic
                 absorption) are allowed. Patients who have received systemic corticosteroids ≤ 30 days
                 prior to starting study drug will be excluded.
    
              -  No other prior malignancy is allowed except for the following:
    
                   -  Adequately treated basal cell or squamous cell skin cancer
    
                   -  In situ cervical cancer
    
                   -  Any other cancer from which the patient has been disease free for at least 3
                      years.
    
              -  Pregnant or breast feeding.
    
              -  Known to be HIV positive.
    
              -  Known current or a history of hepatitis B or C virus, including chronic and dormant
                 states, unless disease has been treated and confirmed cleared.
    
              -  Major surgery within 4 weeks of initiation of study drug.
    
              -  Have not recovered to ≤ Grade 1 or tolerable Grade 2 adverse events (AEs) due to
                 agents administered ≥ 28 days earlier, as documented by the treating investigator.
    
              -  Currently enrolled in any other clinical protocol or investigational trial that
                 involves administration of experimental therapy and/or therapeutic devices, or
                 investigational drug.
    
              -  Not able to comply with the treatment schedule and study procedures for any reason.
    
              -  Have stage IV BC.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:Accepts Healthy Volunteers

    Primary Outcome Measures

    Measure:Rate of HER2 Immune Activation
    Time Frame:Up to 5 years
    Safety Issue:
    Description:HER2 immune activation will be assessed by cluster of differentiation 4 (CD4)+ T-Helper Cell Type 1 (Th1) response assay, as examined in unexpanded peripheral blood mononuclear cells pulsed ex vivo with 6 Major Histocompatibility Complex (MHC) II HER2 peptides. Activation will be measured in peripheral blood by the summation of spots (i.e., ELISPOT for IFN-γ, IL-4, and IL-10) for 6 distinct peptides and reported as total SFC/10^6 cells.

    Secondary Outcome Measures

    Measure:Rate of Restored anti-HER2 CD4 Th1 at 5 Years
    Time Frame:Up to 5 years
    Safety Issue:
    Description:Assessment of the baseline anti-HER2 CD4 low response percentage after prior vaccination with HER2-DC1 vaccine. Anti-HER2 CD4 Th1 will be measured by simple ELISPOT using peripheral blood at study entry and every 12 months for a total of 5 years. High anti-HER2 CD4 immunity is defined by ELISPOT as low response to individual HER2 peptide > 50 Spot-Forming Cells (SFCs)/2 x 10^5 peripheral blood mononuclear cells.
    Measure:Rate of Treatment Emergent Adverse Events
    Time Frame:Up to 5 years
    Safety Issue:
    Description:Serious adverse events will be recorded for 100 days after study treatment. Adverse events will follow National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

    Trial Keywords

    • nonmetastatic
    • classic HER2
    • Nonmetastatic classic HER2

    Last Updated