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Vaccine Therapy in Treating Patients With HER2-Negative Stage III-IV Breast Cancer

Primary Purpose

HER2 Negative Breast Carcinoma, Recurrent Breast Carcinoma, Stage IIIA Breast Cancer

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine
Laboratory Biomarker Analysis
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HER2 Negative Breast Carcinoma

Eligibility Criteria

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

Inclusion Criteria:

  • Patients with stage III-IV HER2 negative breast cancer treated with primary or salvage therapy and now have:

    • No evidence of disease (NED), or
    • Stable bone only disease
  • Patients who have completed standard of care and recovered with mild to no residual toxicity from recent therapy
  • Patients must be at least 28 days post cytotoxic chemotherapy, and/or monoclonal antibody therapy (excluding bone-directed therapy), prior to enrollment
  • Patients must be at least 28 days post systemic steroids prior to enrollment
  • Patients on bisphosphonates, denosumab, and/or endocrine therapy are eligible
  • Patients must have Eastern Cooperative Oncology Group (ECOG) performance status score of =< 1
  • Patients must have recovered from major infections and/or surgical procedures, and in the opinion of the investigator, not have any significant active concurrent medical illnesses precluding protocol treatment
  • Estimated life expectancy of more than 6 months
  • White blood cells (WBC) >= 3000/mm^3 (within 30 days of first vaccination)
  • Lymphocyte count >= 800/mm^3 (within 30 days of first vaccination)
  • Platelet count >= 75,000/mm^3 (within 30 days of first vaccination)
  • Hemoglobin (Hgb) >= 10 g/dl (within 30 days of first vaccination)
  • Serum creatinine <= 1.2 mg/dl or creatinine clearance > 60 ml/min (within 30 days of first vaccination)
  • Total bilirubin <= 1.5 mg/dl (within 30 days of first vaccination)
  • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) <= 2 times upper limit of normal (ULN) (within 30 days of first vaccination)
  • Blood glucose < 1.5 ULN (within 30 days of first vaccination)
  • All patients who are having sex that can lead to pregnancy must agree to contraception for the duration of study

Exclusion Criteria:

  • Patients with any of the following cardiac conditions:

    • Symptomatic restrictive cardiomyopathy
    • Unstable angina within 4 months prior to enrollment
    • New York Heart Association functional class III-IV heart failure on active treatment
    • Symptomatic pericardial effusion
  • Patients at risk for gastrointestinal bleeding (example: peptic ulcer disease, prolonged daily non-steroidal anti-inflammatory use)
  • Patients with any seizure disorder
  • Patients with any contraindication to receiving rhuGM-CSF based products
  • Patients with any clinically significant autoimmune disease uncontrolled with treatment
  • Patients who are simultaneously enrolled in any other treatment study
  • Patients who are pregnant or breastfeeding

Sites / Locations

  • Fred Hutch/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Arm 1 (STEMVAC)

Arm 2 (STEMVAC)

Arm 3 (STEMVAC)

Arm 4 (STEMVAC)

Arm Description

Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 1 injection ID every 28 days for 3 months. Patients may also receive 2 additional booster STEMVAC vaccines at 3 and 9 months after the third vaccine in the absence of unacceptable toxicity or disease progression.

Patients receive CD105/Yb-1/SOX2/CDH3/M2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 2 injections ID every 28 days for 3 months. Patients may also receive 2 additional booster STEMVAC vaccines at 3 and 9 months after the third vaccine in the absence of unacceptable toxicity or disease progression.

Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 3 injections ID every 28 days for 3 months. Patients may also receive 2 additional booster STEMVAC vaccines at 3 and 9 months after the third vaccine in the absence of unacceptable toxicity or disease progression.

Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 2 injections ID every 28 days for 3 months. Patients may also receive 1 additional STEMVAC vaccine at 3 months after the third vaccine in the absence of unacceptable toxicity or disease progression.

Outcomes

Primary Outcome Measures

Incidence of toxicity per Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events version 4.0
The type and grade of toxicities noted during the immunization regimen will be summarized. Adverse events noted by the investigator/designated clinical research staff will be tabulated according to the affected body system. Descriptive statistics will be used to summarize changes from baseline in clinical and/or laboratory parameters.
Immunologic efficacy defined as achievement of a statistically significant increase in Th1 cell immunity for at least 50% of the immunizing antigens as compared to baseline

Secondary Outcome Measures

Memory Th1 dominant immune response to all five antigens over time
Modulation of T-regulatory (Treg) cells with vaccination
Treg defined as present or absent, and the probability will be estimated as a simple proportion.
Modulation of MDSC with vaccination
MDSC defined as present or absent, and the probability will be estimated as a simple proportion.
STEMVAC specific Type 1 immune response
Will detect if STEMVAC specific Type 1 immune response would be negatively correlated with the type II bacterial-tumor antigen (Bac-TA) specific responses. Statistical strategies will be used to assess the incidence and breadth of vaccine induced immunity as related to the levels of Bac-TA Th2 (Arm 4). For magnitude, the initial analysis could include two-tailed Pearson's correlation or even two tailed T tests between clear responder and non-responders. Specific organisms in the gut microbiome may prevent the development of tumor specific Type I immunity after vaccination, and will be evaluated by flow cytometry of peripheral blood mononuclear cells. Analysis could identify a blood based biomarker (Bac-TA responses) that could identify patients who would be less responsive to immune modulation and will be assessed by shotgun metagenomic sequencing.
Bac-TA cross-reactive T-cells
Will evaluate whether organisms associated with Bac-TA cross-reactive T-cells are represented in the patient's microbiome. Will be assessed by collecting stool with the OMNIgene-GUT collection Kits (DNA Genotek) (Arm 4). Analysis could identify a blood based biomarker (Bac-TA responses) that could identify patients who would be less responsive to immune modulation and will be assessed by shotgun metagenomic sequencing.

Full Information

First Posted
June 3, 2014
Last Updated
July 3, 2023
Sponsor
University of Washington
Collaborators
United States Department of Defense, Breast Cancer Alliance
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1. Study Identification

Unique Protocol Identification Number
NCT02157051
Brief Title
Vaccine Therapy in Treating Patients With HER2-Negative Stage III-IV Breast Cancer
Official Title
A Phase I Trial of the Safety and Immunogenicity of a Multiple Antigen Vaccine (STEMVAC) in HER2 Negative Advanced Stage Breast Cancer Patients
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 2015 (Actual)
Primary Completion Date
November 25, 2022 (Actual)
Study Completion Date
February 10, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Washington
Collaborators
United States Department of Defense, Breast Cancer Alliance

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This phase I trial studies the side effects and best dose of multiantigen deoxyribonucleic acid (DNA) plasmid-based vaccine in treating patients with human epidermal growth factor receptor 2 (HER2)-negative stage III-IV breast cancer. Multiantigen DNA plasmid-based vaccine may target immunogenic proteins expressed in breast cancer stem cells which are the component of breast cancer that is resistant to chemotherapy and has the ability to spread. Vaccines made from DNA may help the body build an effective immune response to kill tumor cells.
Detailed Description
OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 4 arms. Arm 1: Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine with recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) as 1 injection intradermally (ID) every 28 days for 3 months. Patients may also receive 2 additional booster STEMVAC vaccines at 3 and 9 months after the third vaccine in the absence of unacceptable toxicity or disease progression. ARM 2: Patients receive CD105/Yb-1/SOX2/CDH3/M2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 2 injections ID every 28 days for 3 months. Patients may also receive 2 additional booster STEMVAC vaccines at 3 and 9 months after the third vaccine in the absence of unacceptable toxicity or disease progression. ARM 3: Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 3 injections ID every 28 days for 3 months. Patients may also receive 2 additional booster STEMVAC vaccines at 3 and 9 months after the third vaccine in the absence of unacceptable toxicity or disease progression. ARM 4: Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 2 injections ID every 28 days for 3 months. Patients may also receive 1 additional STEMVAC vaccine at 3 months after the third vaccine in the absence of unacceptable toxicity or disease progression. After completion of study treatment, patients are followed up twice yearly for up to 5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HER2 Negative Breast Carcinoma, Recurrent Breast Carcinoma, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer, Stage III Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
42 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1 (STEMVAC)
Arm Type
Experimental
Arm Description
Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 1 injection ID every 28 days for 3 months. Patients may also receive 2 additional booster STEMVAC vaccines at 3 and 9 months after the third vaccine in the absence of unacceptable toxicity or disease progression.
Arm Title
Arm 2 (STEMVAC)
Arm Type
Experimental
Arm Description
Patients receive CD105/Yb-1/SOX2/CDH3/M2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 2 injections ID every 28 days for 3 months. Patients may also receive 2 additional booster STEMVAC vaccines at 3 and 9 months after the third vaccine in the absence of unacceptable toxicity or disease progression.
Arm Title
Arm 3 (STEMVAC)
Arm Type
Experimental
Arm Description
Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 3 injections ID every 28 days for 3 months. Patients may also receive 2 additional booster STEMVAC vaccines at 3 and 9 months after the third vaccine in the absence of unacceptable toxicity or disease progression.
Arm Title
Arm 4 (STEMVAC)
Arm Type
Experimental
Arm Description
Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 2 injections ID every 28 days for 3 months. Patients may also receive 1 additional STEMVAC vaccine at 3 months after the third vaccine in the absence of unacceptable toxicity or disease progression.
Intervention Type
Biological
Intervention Name(s)
CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine
Other Intervention Name(s)
CD105/Yb-1/SOX2/CDH3/MDM2 Plasmid Vaccine, STEMVAC, STEMVAC Th1 Polyepitope Plasmid-based Vaccine
Intervention Description
Given ID
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Incidence of toxicity per Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events version 4.0
Description
The type and grade of toxicities noted during the immunization regimen will be summarized. Adverse events noted by the investigator/designated clinical research staff will be tabulated according to the affected body system. Descriptive statistics will be used to summarize changes from baseline in clinical and/or laboratory parameters.
Time Frame
Up to 1 month after last vaccine
Title
Immunologic efficacy defined as achievement of a statistically significant increase in Th1 cell immunity for at least 50% of the immunizing antigens as compared to baseline
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Memory Th1 dominant immune response to all five antigens over time
Time Frame
Up to 12 months
Title
Modulation of T-regulatory (Treg) cells with vaccination
Description
Treg defined as present or absent, and the probability will be estimated as a simple proportion.
Time Frame
Up to 12 months
Title
Modulation of MDSC with vaccination
Description
MDSC defined as present or absent, and the probability will be estimated as a simple proportion.
Time Frame
Up to 12 months
Title
STEMVAC specific Type 1 immune response
Description
Will detect if STEMVAC specific Type 1 immune response would be negatively correlated with the type II bacterial-tumor antigen (Bac-TA) specific responses. Statistical strategies will be used to assess the incidence and breadth of vaccine induced immunity as related to the levels of Bac-TA Th2 (Arm 4). For magnitude, the initial analysis could include two-tailed Pearson's correlation or even two tailed T tests between clear responder and non-responders. Specific organisms in the gut microbiome may prevent the development of tumor specific Type I immunity after vaccination, and will be evaluated by flow cytometry of peripheral blood mononuclear cells. Analysis could identify a blood based biomarker (Bac-TA responses) that could identify patients who would be less responsive to immune modulation and will be assessed by shotgun metagenomic sequencing.
Time Frame
Up to 12 months
Title
Bac-TA cross-reactive T-cells
Description
Will evaluate whether organisms associated with Bac-TA cross-reactive T-cells are represented in the patient's microbiome. Will be assessed by collecting stool with the OMNIgene-GUT collection Kits (DNA Genotek) (Arm 4). Analysis could identify a blood based biomarker (Bac-TA responses) that could identify patients who would be less responsive to immune modulation and will be assessed by shotgun metagenomic sequencing.
Time Frame
Up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with stage III-IV HER2 negative breast cancer treated with primary or salvage therapy and now have: No evidence of disease (NED), or Stable bone only disease Patients who have completed standard of care and recovered with mild to no residual toxicity from recent therapy Patients must be at least 28 days post cytotoxic chemotherapy, and/or monoclonal antibody therapy (excluding bone-directed therapy), prior to enrollment Patients must be at least 28 days post systemic steroids prior to enrollment Patients on bisphosphonates, denosumab, and/or endocrine therapy are eligible Patients must have Eastern Cooperative Oncology Group (ECOG) performance status score of =< 1 Patients must have recovered from major infections and/or surgical procedures, and in the opinion of the investigator, not have any significant active concurrent medical illnesses precluding protocol treatment Estimated life expectancy of more than 6 months White blood cells (WBC) >= 3000/mm^3 (within 30 days of first vaccination) Lymphocyte count >= 800/mm^3 (within 30 days of first vaccination) Platelet count >= 75,000/mm^3 (within 30 days of first vaccination) Hemoglobin (Hgb) >= 10 g/dl (within 30 days of first vaccination) Serum creatinine <= 1.2 mg/dl or creatinine clearance > 60 ml/min (within 30 days of first vaccination) Total bilirubin <= 1.5 mg/dl (within 30 days of first vaccination) Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) <= 2 times upper limit of normal (ULN) (within 30 days of first vaccination) Blood glucose < 1.5 ULN (within 30 days of first vaccination) All patients who are having sex that can lead to pregnancy must agree to contraception for the duration of study Exclusion Criteria: Patients with any of the following cardiac conditions: Symptomatic restrictive cardiomyopathy Unstable angina within 4 months prior to enrollment New York Heart Association functional class III-IV heart failure on active treatment Symptomatic pericardial effusion Patients at risk for gastrointestinal bleeding (example: peptic ulcer disease, prolonged daily non-steroidal anti-inflammatory use) Patients with any seizure disorder Patients with any contraindication to receiving rhuGM-CSF based products Patients with any clinically significant autoimmune disease uncontrolled with treatment Patients who are simultaneously enrolled in any other treatment study Patients who are pregnant or breastfeeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mary Disis
Organizational Affiliation
Fred Hutch/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutch/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Vaccine Therapy in Treating Patients With HER2-Negative Stage III-IV Breast Cancer

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