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Concurrent WOKVAC Vaccination, Chemotherapy, and HER2-Targeted Monoclonal Antibody Therapy Before Surgery for the Treatment of Patients With 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: NCT04329065
Recruitment Status : Recruiting
First Posted : April 1, 2020
Last Update Posted : August 3, 2022
Sponsor:
Collaborator:
United States Department of Defense
Information provided by (Responsible Party):
University of Washington

Brief Summary:
This phase II trial studies the immunologic response and side effects of using the WOKVAC vaccine in combination with chemotherapy and HER2-targeted monoclonal antibody therapy before surgery in treating patients with breast cancer. Vaccines like WOKVAC are made from tumor-associated antigens which may help the body build an effective immune response to kill tumor cells. Chemotherapy drugs, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Trastuzumab and pertuzumab are forms of targeted therapy because they work by attaching themselves to specific molecules (receptors) on the surface of tumor cells, known as HER2 receptors. When trastuzumab and pertuzumab attach to HER2 receptors, the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the body's immune system. Giving the WOKVAC vaccine at the same time (concurrently) with paclitaxel, trastuzumab, and pertuzumab before surgery may kill more tumor cells.

Condition or disease Intervention/treatment Phase
Anatomic Stage I Breast Cancer AJCC v8 Anatomic Stage IA Breast Cancer AJCC v8 Anatomic Stage IB Breast Cancer AJCC v8 Anatomic Stage II Breast Cancer AJCC v8 Anatomic Stage IIA Breast Cancer AJCC v8 Anatomic Stage IIB Breast Cancer AJCC v8 Anatomic Stage III Breast Cancer AJCC v8 Anatomic Stage IIIA Breast Cancer AJCC v8 Anatomic Stage IIIB Breast Cancer AJCC v8 Anatomic Stage IIIC Breast Cancer AJCC v8 Prognostic Stage I Breast Cancer AJCC v8 Prognostic Stage IA Breast Cancer AJCC v8 Prognostic Stage IB Breast Cancer AJCC v8 Prognostic Stage II Breast Cancer AJCC v8 Prognostic Stage IIA Breast Cancer AJCC v8 Prognostic Stage IIB Breast Cancer AJCC v8 Prognostic Stage III Breast Cancer AJCC v8 Prognostic Stage IIIA Breast Cancer AJCC v8 Prognostic Stage IIIB Breast Cancer AJCC v8 Prognostic Stage IIIC Breast Cancer AJCC v8 Biological: pUMVC3-IGFBP2-HER2-IGF1R Plasmid DNA Vaccine Drug: Paclitaxel Biological: Trastuzumab Biological: Pertuzumab Phase 2

Detailed Description:

OUTLINE

Patients receive WOKVAC intradermally (ID) on day 13. Treatment repeats for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive paclitaxel via infusion on days 1, 8, and 15, and trastuzumab intravenously (IV) and pertuzumab IV on day 1. The chemo and trastuzumab and pertuzumab will most likely be given by their own oncologist per standard of care. Treatment repeats for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up annually for up to 5 years from enrollment.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Concurrent WOKVAC Vaccination With Neoadjuvant Chemotherapy and HER2-Targeted Monoclonal Antibody Therapy
Actual Study Start Date : April 20, 2022
Estimated Primary Completion Date : June 30, 2023
Estimated Study Completion Date : June 30, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vaccines

Arm Intervention/treatment
Experimental: Treatment (WOKVAC, paclitaxel, trastuzumab, pertuzumab)
Patients receive WOKVAC ID on day 13. Treatment repeats for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive paclitaxel via infusion on days 1, 8, and 15, and trastuzumab IV and pertuzumab IV on day 1. Treatment repeats for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
Biological: pUMVC3-IGFBP2-HER2-IGF1R Plasmid DNA Vaccine
Given ID
Other Names:
  • pUMVC3-IGFBP2-HER2-IGF1R
  • pUMVC3-IGFBP2-HER2-IGF1R Vaccine
  • WOKVAC
  • WOKVAC Vaccine

Drug: Paclitaxel
Given via infusion
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Biological: Trastuzumab
Given IV
Other Names:
  • Anti-c-erbB2 Monoclonal Antibody
  • Anti-ERB-2
  • Anti-erbB2 Monoclonal Antibody
  • Anti-HER2/c-erbB2 Monoclonal Antibody
  • Herceptin
  • Herceptin Biosimilar PF-05280014
  • Herceptin Trastuzumab Biosimilar PF-05280014
  • Herzuma
  • Disulfide with Human-Mouse Monoclonal RhuMab HER2 Light Chain
  • MoAb HER2
  • Monoclonal Antibody c-erb-2
  • Monoclonal Antibody HER2
  • Ogivri
  • Ontruzant
  • rhuMAb HER2
  • Trastuzumab Biosimilar ABP 980
  • Trastuzumab Biosimilar ALT02
  • trastuzumab biosimilar EG12014
  • Trastuzumab Biosimilar HLX02
  • Trastuzumab Biosimilar PF-05280014
  • Trastuzumab Biosimilar SB3
  • Trastuzumab-dkst
  • Trastuzumab-DTTB
  • Trastuzumab-pkrb
  • Trastuzumab-QYYP
  • Trazimera
  • Trastuzumab Biosimilar SIBP-01

Biological: Pertuzumab
Given IV
Other Names:
  • 2C4 Antibody
  • Immunoglobulin G1
  • Anti-(Human V (Receptor)) (Human-Mouse Monoclonal 2C4 Heavy Chain)
  • Disulfide with Human-Mouse Monoclonal 2C4 Kappa-Chain
  • MoAb 2C4
  • Monoclonal Antibody 2C4
  • Omnitarg
  • Perjeta
  • rhuMAb2C4
  • RO4368451
  • Pertuzumab Biosimilar HS627




Primary Outcome Measures :
  1. Enumeration of the number of T-bet+, CD4+, and CD8+ T-cells in tumor infiltrating lymphocytes (TIL) after combination immune-chemotherapy [ Time Frame: Up to completion of surgical resection ]
    Tumor tissue will be collected from prior diagnostic tumor biopsies as well as from an ultrasound guided core needle biopsy performed on day 13 of cycle 3. Tumor biopsies collected pre- and post- trial therapy will be processed and evaluated by immunohistochemistry for differences and changes in T cell content and T cell subtype. Specifically, will evaluate the differences in the presence of T-bet+ CD4+ and CD8+ T cells, a T cell subtype recently recognized to influence both the induced human epidermal growth factor receptor 2 (HER2)-specific cellular immunity and clinical outcomes. Changes in the tumor content of T-bet+ CD4+ and CD8+ T cells between the pre- and post-trial therapy time points will be evaluated.


Secondary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to 5 years ]
    Safety will be assessed per Common Terminology Criteria for Adverse Events version (v)4.0. The type and grade of toxicities noted during the immunization regimen will be summarized. The duration of toxicities will also be summarized using descriptive statistics such as mean and standard deviation. All adverse events noted by the investigator will be tabulated according to the affected body system. The frequency and severity of adverse events will be summarized with a proportion and a 95% confidence interval.

  2. Induction of type 1 helper cell (Th1) immunity against HER2, IGF-1R, and IGFBP2 [ Time Frame: Up to day 13 of cycle 4 (each cycle is 21 days) ]
    Cellular immune response will be defined by the magnitude of the Th1 (interferon-gamma [IFN-g]) versus (vs.) type 2 helper cell (Th2) (IL-10) antigen specific immune response using enzyme-linked immunosorbent spot assay (ELISPOT). Immune responses as measured by IFN-g ELISPOT will be summarized with mean and standard deviation or median and range over time, the change over time will be summarized with graphs, and also analyzed using linear mixed-effects regression models with normalizing transformation if necessary. The proportion of study participants who develop immunity to either of the three antigens will be computed and 95% confidence internal would be generated. The induction of Th1 immunity will be compared against the presence or absence of a complete pathologic response to determine if there is a significant correlation using Pearson r correlation analysis.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • Clinical stage I-III breast cancer, HER2+ (per American Society of Clinical Oncology [ASCO]/College of American Pathologists [CAP] guideline update, 2018), estrogen receptor negative (ER-) (< 5%) and progesterone receptor negative (PR-) (< 5%) and planning to undergo neoadjuvant therapy with paclitaxel, trastuzumab, and pertuzumab
  • Patients who have received prior neoadjuvant chemotherapy are allowed but may only receive paclitaxel, trastuzumab, and pertuzumab for the duration the study
  • Subjects with Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
  • White blood cell (WBC) >= 3000/mm^3 (within 4 weeks of initiating study treatment)
  • Lymphocyte count >= 800/mm^3 (within 4 weeks of initiating study treatment)
  • Absolute neutrophil count (ANC) >= 1,500/ uL (within 4 weeks of initiating study treatment)
  • Platelets >= 75,000/ uL (within 4 weeks of initiating study treatment)
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN), except patients with Gilbert's syndrome in whom total bilirubin must be < 3.0 mg/dL (within 4 weeks of initiating study treatment)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x institutional upper limit of normal (ULN) (within 4 weeks of initiating study treatment)
  • Creatinine =< 2.0 mg/dL or creatinine clearance > 30 ml/min (within 4 weeks of initiating study treatment)
  • Left ventricular ejection fraction (LVEF) >= lower limit of normal for institution performing the multi-gated acquisition (MUGA) or echocardiogram (ECHO) done within 3 months of initiating study treatment
  • Female patients of child-bearing potential must agree to use dual methods of contraception and have a negative urine pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential. Acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. For both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last vaccine
  • Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients with any of the following cardiac conditions:

    • Symptomatic restrictive cardiomyopathy
    • Dilated 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
  • Uncontrolled autoimmune disease requiring active systemic treatment
  • Known hypersensitivity reaction to the granulocyte-macrophage colony stimulating factor (GM-CSF) adjuvant; any known contra-indication to GM-CSF
  • Pregnant or breast feeding
  • Known human immunodeficiency virus (HIV)-positive
  • History of uncontrolled diabetes
  • Known current or a history of hepatitis B or C virus, including chronic and dormant states, unless disease has been treated and confirmed cleared
  • Major surgery within the 4 weeks prior to initiation of study vaccine
  • Current use of immunosuppressive agents or systemic corticosteroids. Topical, ocular, intra-articular, intranasal, inhalational corticosteroids (with minimal systemic absorption) are allowed. Patients who have received systemic corticosteroids =< 30 days prior to starting study drug will be excluded
  • Patient is currently enrolled in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices, or investigational drug
  • Patients may not be receiving any other investigational agents

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): NCT04329065


Contacts
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Contact: Kris Kauno 206-543-9258 kkauno@uw.edu

Locations
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United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Kris Kauno    206-543-9258    kkauno@uw.edu   
Principal Investigator: William Gwin         
Sponsors and Collaborators
University of Washington
United States Department of Defense
Investigators
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Principal Investigator: William Gwin Fred Hutch/University of Washington Cancer Consortium
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Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT04329065    
Other Study ID Numbers: RG1005296
NCI-2020-01662 ( Registry Identifier: NCI / CTRP )
W81XWH-16-1-0385 ( Other Identifier: Department of Defense (DOD) )
10159 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
First Posted: April 1, 2020    Key Record Dates
Last Update Posted: August 3, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Washington:
Breast
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Trastuzumab
Albumin-Bound Paclitaxel
Pertuzumab
Trastuzumab biosimilar HLX02
Antineoplastic Agents, Immunological
Vaccines
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunoglobulin G
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action