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

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ClinicalTrials.gov Identifier: NCT04144023
Recruitment Status : Recruiting
First Posted : October 30, 2019
Last Update Posted : November 28, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Ductal Breast Carcinoma In Situ HER2/Neu Positive Biological: Granulocyte-Macrophage Colony-Stimulating Factor Biological: Multi-epitope HER2 Peptide Vaccine H2NVAC Procedure: Therapeutic Conventional Surgery Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 43 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase IB Trial of Neoadjvuant Multi-Epitope HER2 Peptide Vaccine in Patients With HER2-Expressing DCIS
Actual Study Start Date : April 1, 2019
Estimated Primary Completion Date : June 1, 2023
Estimated Study Completion Date : June 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (multi-epitope HER2 peptide vaccine H2NVAC, GM-CSF)
Prior 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.
Biological: Granulocyte-Macrophage Colony-Stimulating Factor
Given intradermally
Other Names:
  • Colony 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 Factor

Biological: Multi-epitope HER2 Peptide Vaccine H2NVAC
Given intradermally
Other Names:
  • H2NVAC (CN)
  • HER2 Peptide Vaccine H2NVAC (SY),
  • HER2 Specific Helper T-cell Epitope Vaccine H2NVAC (SY)

Procedure: Therapeutic Conventional Surgery
Undergo standard of care surgery




Primary Outcome Measures :
  1. Adverse events [ Time Frame: 2 years ]
    Number of adverse events reported.

  2. Changes in Dose limiting toxicities [ Time Frame: 14 days post vaccination, 2 years ]
    Measured using criteria from the National Cancer Institute's Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events, version 4.0 with grade >= 2 allergic reaction, or changes in left ventricular ejection fraction (LVEF).

  3. Changes in Dose limiting toxicities [ Time Frame: 14 days post vaccination, 2 years ]
    Measured using criteria from the National Cancer Institute's Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events, version 4.0 with grade >= 2 autoimmune reaction, or changes in left ventricular ejection fraction (LVEF).

  4. Changes in Dose limiting toxicities [ Time Frame: 14 days post vaccination, 2 years ]
    Measured using criteria from the National Cancer Institute's Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events, version 4.0 with grade >= 2 injection site reaction manifesting as an ulceration, or changes in left ventricular ejection fraction (LVEF).

  5. Changes in Dose limiting toxicities [ Time Frame: 14 days post vaccination, 2 years ]
    Measured using criteria from the National Cancer Institute's Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events, version 4.0 with grade >= 2 neurologic problem, or changes in left ventricular ejection fraction (LVEF).

  6. Changes in Dose limiting toxicities [ Time Frame: 14 days post vaccination, 2 years ]
    Measured using criteria from the National Cancer Institute's Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events, version 4.0 with grade 3+ toxicity, or changes in left ventricular ejection fraction (LVEF).



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:   Female
Accepts Healthy Volunteers:   No
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

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 ClinicalTrials.gov identifier (NCT number): NCT04144023


Locations
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United States, Florida
Mayo Clinic in Florida Recruiting
Jacksonville, Florida, United States, 32224-9980
Contact: Saranya Chumsri    904-953-0707    chumsri.saranya@mayo.edu   
Principal Investigator: Saranya Chumsri         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Amy C. Degnim    507-284-4499    degnim.amy@mayo.edu   
Principal Investigator: Amy C. Degnim         
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Amy C Degnim Mayo Clinic

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Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT04144023     History of Changes
Other Study ID Numbers: MC1713
NCI-2019-07002 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1713 ( Other Identifier: Mayo Clinic )
P30CA015083 ( U.S. NIH Grant/Contract )
First Posted: October 30, 2019    Key Record Dates
Last Update Posted: November 28, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Breast Neoplasms
Carcinoma in Situ
Carcinoma, Ductal, Breast
Breast Carcinoma In Situ
Carcinoma, Intraductal, Noninfiltrating
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Carcinoma, Ductal
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Vaccines
Sargramostim
Immunologic Factors
Physiological Effects of Drugs