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

Primary Purpose

Breast Ductal Carcinoma In Situ

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Granulocyte-Macrophage Colony-Stimulating Factor
Multi-epitope HER2 Peptide Vaccine H2NVAC
Therapeutic Conventional Surgery
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Ductal Carcinoma In Situ

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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 if they chose to have this collected
    • 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

    • Note: suspected microinvasion or definite microinvasion (< 0.1 mm invasion) on core biopsy is allowed
  • Patients will be asked to have an additional research biopsy prior to the first vaccination. This is not mandatory for participation
  • Patients must have evidence of at least 1.0 cm of disease extent based on mammogram, ultrasound, or magnetic resonance (MRI) 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

Sites / Locations

  • Mayo Clinic in FloridaRecruiting
  • Mayo Clinic in RochesterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (multi-epitope HER2 peptide vaccine H2NVAC, GM-CSF)

Arm Description

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.

Outcomes

Primary Outcome Measures

Adverse events
Number of adverse events reported.
Dose limiting toxicities
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, grade >= 2 autoimmune reaction, grade >= 2 injection site reaction manifesting as an ulceration, grade >= 2 neurologic problem, grade 3+ toxicity, or any one of following changes in left ventricular ejection fraction (LVEF).

Secondary Outcome Measures

Full Information

First Posted
October 28, 2019
Last Updated
July 7, 2023
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04144023
Brief Title
A Vaccine (H2NVAC) Before Surgery for the Treatment of HER2-Expressing Ductal Carcinoma In Situ
Official Title
A Phase IB Trial of Neoadjuvant Multi-Epitope HER2 Peptide Vaccine in Patients With HER2-Expressing DCIS
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 27, 2019 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Ductal Carcinoma In Situ

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
43 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (multi-epitope HER2 peptide vaccine H2NVAC, GM-CSF)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Granulocyte-Macrophage Colony-Stimulating Factor
Other Intervention Name(s)
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
Intervention Description
Given intradermally
Intervention Type
Biological
Intervention Name(s)
Multi-epitope HER2 Peptide Vaccine H2NVAC
Other Intervention Name(s)
H2NVAC, HER2 Peptide Vaccine H2NVAC, HER2 Specific Helper T-cell Epitope Vaccine H2NVAC
Intervention Description
Given intradermally
Intervention Type
Procedure
Intervention Name(s)
Therapeutic Conventional Surgery
Intervention Description
Undergo standard of care surgery
Primary Outcome Measure Information:
Title
Adverse events
Description
Number of adverse events reported.
Time Frame
2 years
Title
Dose limiting toxicities
Description
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, grade >= 2 autoimmune reaction, grade >= 2 injection site reaction manifesting as an ulceration, grade >= 2 neurologic problem, grade 3+ toxicity, or any one of following changes in left ventricular ejection fraction (LVEF).
Time Frame
14 days post vaccination, 2 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 if they chose to have this collected 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 Note: suspected microinvasion or definite microinvasion (< 0.1 mm invasion) on core biopsy is allowed Patients will be asked to have an additional research biopsy prior to the first vaccination. This is not mandatory for participation Patients must have evidence of at least 1.0 cm of disease extent based on mammogram, ultrasound, or magnetic resonance (MRI) 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amy C Degnim
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224-9980
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinical Trials Referral Office
Phone
855-766-0015
Email
mayocliniccancerstudies@mayo.edu
First Name & Middle Initial & Last Name & Degree
Saranya Chumsri, M.D.
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinical Trials Referral Office
Phone
855-776-0015
Email
mayocliniccancerstudies@mayo.edu
First Name & Middle Initial & Last Name & Degree
Amy C. Degnim, M.D.

12. IPD Sharing Statement

Learn more about this trial

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

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