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Trial record 1 of 1 for:    STEMVAC
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Vaccine Therapy in Treating Patients With HER2-Negative Stage III-IV Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02157051
Recruitment Status : Recruiting
First Posted : June 5, 2014
Last Update Posted : October 12, 2020
Sponsor:
Collaborators:
United States Department of Defense
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Washington

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.

Condition or disease Intervention/treatment Phase
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 Biological: CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine Other: Laboratory Biomarker Analysis Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 2015
Estimated Primary Completion Date : February 10, 2022
Estimated Study Completion Date : February 10, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Arm 1 (STEMVAC)
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.
Biological: CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine
Given ID
Other Names:
  • CD105/Yb-1/SOX2/CDH3/MDM2 Plasmid Vaccine
  • STEMVAC
  • STEMVAC Th1 Polyepitope Plasmid-based Vaccine

Other: Laboratory Biomarker Analysis
Correlative studies

Experimental: Arm 2 (STEMVAC)
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.
Biological: CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine
Given ID
Other Names:
  • CD105/Yb-1/SOX2/CDH3/MDM2 Plasmid Vaccine
  • STEMVAC
  • STEMVAC Th1 Polyepitope Plasmid-based Vaccine

Other: Laboratory Biomarker Analysis
Correlative studies

Experimental: Arm 3 (STEMVAC)
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.
Biological: CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine
Given ID
Other Names:
  • CD105/Yb-1/SOX2/CDH3/MDM2 Plasmid Vaccine
  • STEMVAC
  • STEMVAC Th1 Polyepitope Plasmid-based Vaccine

Other: Laboratory Biomarker Analysis
Correlative studies

Experimental: Arm 4 (STEMVAC)
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.
Biological: CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine
Given ID
Other Names:
  • CD105/Yb-1/SOX2/CDH3/MDM2 Plasmid Vaccine
  • STEMVAC
  • STEMVAC Th1 Polyepitope Plasmid-based Vaccine

Other: Laboratory Biomarker Analysis
Correlative studies




Primary Outcome Measures :
  1. Incidence of toxicity per Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 1 month after last vaccine ]
    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.

  2. 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 Measures :
  1. Memory Th1 dominant immune response to all five antigens over time [ Time Frame: Up to 12 months ]
  2. Modulation of T-regulatory (Treg) cells with vaccination [ Time Frame: Up to 12 months ]
    Treg defined as present or absent, and the probability will be estimated as a simple proportion.

  3. Modulation of MDSC with vaccination [ Time Frame: Up to 12 months ]
    MDSC defined as present or absent, and the probability will be estimated as a simple proportion.

  4. STEMVAC specific Type 1 immune response [ Time Frame: Up to 12 months ]
    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.

  5. Bac-TA cross-reactive T-cells [ Time Frame: Up to 12 months ]
    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.



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:   All
Accepts Healthy Volunteers:   No
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

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): NCT02157051


Contacts
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Contact: Mary Disis 206-616-1823 ndisis@u.washington.edu

Locations
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United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Mary L. Disis    206-616-1823    ndisis@u.washington.edu   
Principal Investigator: Mary L. Disis         
Sponsors and Collaborators
University of Washington
United States Department of Defense
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Mary Disis Fred Hutch/University of Washington Cancer Consortium
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Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT02157051    
Other Study ID Numbers: 9140
NCI-2014-01070 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
137
9140 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
RG1715017 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
First Posted: June 5, 2014    Key Record Dates
Last Update Posted: October 12, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Carcinoma
Breast Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs