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:

Suspended

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.
  • HER2 DC1 Vaccine

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with a diagnosis of nonmetastatic or metastatic breast cancer in complete
             clinicla response 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).

          -  Patients with nonmetastatic HER posBC 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. Note:
             antiestrogen therapy is permitted while on trial.

          -  Patients with diagnosis of metastatic HER2 pos breast cancer must have complete tumor
             response to current treatment per RECIST 1.1 and completed all standard-of-care
             chemotherapy. Note: maintenance treatment with approved HER2-targeted agents and/or
             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.
      
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:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • nonmetastatic
  • classic HER2
  • Nonmetastatic classic HER2

Last Updated

February 6, 2020