Clinical Trials /

A Vaccine (H2NVAC) Before Surgery for the Treatment of HER2-Expressing Ductal Carcinoma In Situ

NCT04144023

Description:

This phase Ib trial studies the side effects and best dose of a vaccine called H2NVAC before surgery in treating patients with HER2 expressing ductal carcinoma in situ. H2NVAC is a vaccine designed to stimulate specialized white blood cells in hopes of increasing immune response and protecting against breast cancer.

Related Conditions:
  • Ductal Carcinoma In Situ
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Vaccine (H2NVAC) Before Surgery for the Treatment of HER2-Expressing Ductal Carcinoma In Situ
  • Official Title: A Phase IB Trial of Neoadjvuant Multi-Epitope HER2 Peptide Vaccine in Patients With HER2-Expressing DCIS

Clinical Trial IDs

  • ORG STUDY ID: MC1713
  • SECONDARY ID: NCI-2019-07002
  • SECONDARY ID: MC1713
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT04144023

Conditions

  • Ductal Breast Carcinoma In Situ
  • HER2/Neu Positive

Interventions

DrugSynonymsArms
Granulocyte-Macrophage Colony-Stimulating FactorColony Stimulating Factor 2, Colony Stimulating Factor, Granulocyte-Macrophage, Colony-Stimulating Factor, Colony-Stimulating Factor 2, CSF, CSF2, GM CSF, GM-CSF, GMCSF, Granulocyte Macrophage Colony Stimulating Factor, Granulocyte Macrophage Colony-Stimulating Factor, Granulocyte-Macrophage Colony Stimulating FactorTreatment (multi-epitope HER2 peptide vaccine H2NVAC, GM-CSF)
Multi-epitope HER2 Peptide Vaccine H2NVACH2NVAC (CN), HER2 Peptide Vaccine H2NVAC (SY),, HER2 Specific Helper T-cell Epitope Vaccine H2NVAC (SY)Treatment (multi-epitope HER2 peptide vaccine H2NVAC, GM-CSF)

Purpose

This phase Ib trial studies the side effects and best dose of a vaccine called H2NVAC before surgery in treating patients with HER2 expressing ductal carcinoma in situ. H2NVAC is a vaccine designed to stimulate specialized white blood cells in hopes of increasing immune response and protecting against breast cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the safety and tolerability of multi-epitope HER2 peptide vaccine H2NVAC
      (H2NVAC) given every 2 weeks for 4 cycles in patients with HER2 expressing ductal carcinoma
      in situ (DCIS) prior to surgery.

      II. To determine the dose level of H2NVAC with maximum systemic and intratumoral
      immunogenicity as measured by activated HER2-specific T lymphocytes or high-affinity
      antibodies.

      SECONDARY OBJECTIVES:

      I. To determine intratumoral immunogenicity of H2NVAC in patients with HER2-expressing DCIS.

      II. To assess the complete pathological response after 4 cycles of neoadjuvant H2NVAC.

      III. To assess the systemic immunogenicity of H2NVAC in patients with HER2-expressing DCIS.

      IV. To assess changes in HER2 expression in the DCIS after 4 cycles of neoadjuvant H2NVAC.

      V. To assess the distribution of the helper T cell response among T helper cell
      differentiation states.

      OUTLINE: This is a dose-escalation study of multi-epitope HER2 peptide vaccine H2NVAC.

      Prior to standard of care surgery, patients receive granulocyte macrophage-colony-stimulating
      factor (GM-CSF) admixed with multi-epitope HER2 peptide vaccine H2NVAC intradermally on day
      1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression
      or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 3, 6, and 12 months after
      surgery and optionally at 18 and 24 months after surgery.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (multi-epitope HER2 peptide vaccine H2NVAC, GM-CSF)ExperimentalPrior to standard of care surgery, patients receive GM-CSF admixed with multi-epitope HER2 peptide vaccine H2NVAC intradermally on day 1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Multi-epitope HER2 Peptide Vaccine H2NVAC

Eligibility Criteria

        Inclusion Criteria:

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  Patients must not have received any prior therapy for current DCIS

               -  Note: Patients who received tamoxifen, raloxifene, aromatase inhibitor or another
                  agent for prevention of breast cancer may be included as long as the patient has
                  discontinued the treatment at least 2 months prior to baseline study biopsy

               -  Note: Concurrent use of endocrine therapy during the vaccination/preoperative
                  period is not allowed. However, standard adjuvant endocrine therapy with
                  tamoxifen or aromatase inhibitor after completion of vaccination and surgery is
                  allowed

          -  Any degree of HER2 expression as performed on the diagnostic clinical biopsy defined
             by immunohistochemistry +1, +2, or +3

          -  Histologically confirmed un-resected operable ductal carcinoma in situ with no
             evidence of lymph node involvement or distant metastasis

          -  Patients must be agreeable to have an additional research biopsy prior to the first
             vaccination

          -  Patients must have evidence of at least 1.0 cm of disease extent based on mammogram or
             ultrasound imaging

          -  Absolute neutrophil count (ANC) >= 1500/mm^3 (less than or equal to 28 days prior to
             registration)

          -  Platelet count >= 75,000/mm^3 (less than or equal to 28 days prior to registration)

          -  Hemoglobin >= 9.0 g/dL (less than or equal to 28 days prior to registration)

          -  Creatinine =< 2 x upper limit of normal (ULN) (less than or equal to 28 days prior to
             registration)

          -  Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2
             x ULN (less than or equal to 28 days prior to registration)

          -  Albumin >= 3 g/dL (less than or equal to 28 days prior to registration)

          -  Negative serum pregnancy test done =< 7 days prior to Registration, for women of
             childbearing potential only

          -  Willing to employ adequate contraception from the time of Registration through 6
             months after the final vaccine cycle

               -  Note: Adequate contraception methods include birth control pills, barrier device,
                  intrauterine device

          -  Capable of understanding the investigative nature, potential risks, and benefits of
             the study

          -  Capable of providing valid informed consent

          -  Willing to return to enrolling institution for all study visits (immunizations, blood
             draws, etc)

          -  Willing to provide blood samples for correlative research purposes

          -  Willing to receive a tetanus vaccination if subject has not had one within the past
             year

        Exclusion Criteria:

          -  Any of the following because this study involves an investigational agent whose
             genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are
             unknown:

               -  Pregnant women

               -  Nursing women unwilling to stop breast feeding

               -  Women of child bearing potential who are unwilling to employ adequate
                  contraception from the time of registration through 6 months after the final
                  vaccine cycle

          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens

          -  Immunocompromised patients including patients known to be human immunodeficiency virus
             (HIV) positive or those on chronic steroids

               -  Note: Must be off systemic steroids greater than or equal to 90 days prior to
                  Registration. However, topical steroids, inhalants or steroid eye drops are
                  permitted

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Uncontrolled acute or chronic medical conditions including, but not limited to the
             following:

               -  Active infection requiring antibiotics

               -  Congestive heart failure with New York Heart Association class III or IV moderate
                  to severe objective evidence of cardiovascular disease

               -  Myocardial infarction or stroke less than or equal to 6 months prior to
                  registration

          -  Receiving any other investigational agent

          -  Other active malignancy at time of registration or less than or equal to the last
             three years prior to registration. EXCEPTIONS: Non-melanoma skin cancer or
             carcinoma-in-situ (e.g. of cervix, prostate)

               -  NOTE: If there is a history of prior malignancy, they must not be receiving other
                  specific treatment (cytotoxics, monoclonal antibodies, small molecule inhibitors)
                  for their cancer

          -  Known history of autoimmune disease, including type I diabetes

          -  Any prior hypersensitivity or adverse reaction to GM-CSF

          -  History of trastuzumab-related cardiac toxicity requiring interruption or
             discontinuation of therapy, even if left ventricular ejection fraction (LVEF) fully
             recovered

          -  Baseline LVEF with a value below 55%

          -  Failure to fully recover from acute, reversible effects of prior chemotherapy
             regardless of interval since last treatment

          -  History of myocardial infarction =< 168 days (6 months) prior to registration, or
             congestive heart failure requiring use of ongoing maintenance therapy for life
             threatening ventricular arrhythmias

          -  History of ipsilateral radiation to the current affected breast with DCIS
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse events
Time Frame:2 years
Safety Issue:
Description:Number of adverse events reported.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mayo Clinic

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