Vaccine Therapy in Preventing Cancer Recurrence in Patients With Non-Metastatic, Node Positive, HER2 Negative Breast Cancer That is in Remission

NCT ID: NCT02780401

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-02
• Study Completion Date: 2022-10-08

Brief Summary

This phase I trial studies the side effects and best dose of a vaccine therapy in preventing cancer from coming back in patients with non-metastatic, node positive, human epidermal growth factor receptor (HER)2 negative breast cancer in which all signs and symptoms have disappeared. Vaccines made from deoxyribonucleic acid (DNA) may help the body build an effective immune response to kill tumor cells. Giving multiple vaccinations may make a stronger immune response and prevent or delay the return of cancer.

Detailed Description

OUTLINE: This is a dose escalation study of WOKVAC.

Patients receive WOKVAC with sargramostim intradermally (ID) on day 1. Courses repeat every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Patients with axillary lymph node dissection (ALND) will have vaccine administered to the contralateral arm. Patients with bilateral ALND will have vaccine administered in the thigh. As much as possible each vaccine dose will be given within the same draining lymph node site. Patients will be monitored for a minimum of 60 minutes post vaccine administration.

After completion of study treatment, patients are followed up at 1 month, 6 months and annually for up to 5 years thereafter.

Conditions

HER2/Neu Negative; No Evidence of Disease; One or More Positive Axillary Nodes; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Treatment (WOKVAC with sargramostim)

Patients receive WOKVAC with sargramostim ID on day 1. Courses repeat every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Patients with ALND will have vaccine administered to the contralateral arm. Patients with bilateral ALND will have vaccine administered in the thigh. As much as possible each vaccine dose will be given within the same draining lymph node site. Patients will be monitored for a minimum of 60 minutes post vaccine administration.

Group Type: EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

pUMVC3-IGFBP2-HER2-IGF1R Plasmid DNA Vaccine

Intervention Type: BIOLOGICAL

Given ID

Sargramostim

Intervention Type: BIOLOGICAL

Given ID

Interventions

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

pUMVC3-IGFBP2-HER2-IGF1R Plasmid DNA Vaccine

Given ID

Intervention Type: BIOLOGICAL

Sargramostim

Given ID

Intervention Type: BIOLOGICAL

Other Intervention Names

pUMVC3-IGFBP2-HER2-IGF1R; pUMVC3-IGFBP2-HER2-IGF1R Vaccine; WOKVAC; WOKVAC Vaccine; 23-L-Leucinecolony-Stimulating Factor 2; DRG-0012; Leukine; Prokine; rhu GM-CFS; Sagramostim; Sargramostatin

Eligibility Criteria

Inclusion Criteria

• Patients with non-metastatic, node positive, HER2 negative breast cancer, confirmed by pathology report, who are in remission and defined as having no evidence of disease (NED); HER2 negative is defined as

• 0-1+ HER2 expression by immunohistochemistry (IHC) OR
• Fluorescence in situ hybridization (FISH) negative OR
• HER2 2+ and FISH negative
• Patients must be at least 28 days post cytotoxic chemotherapy, radiotherapy, monoclonal antibody and/or other biologic therapy, prior to enrollment; patients on bisphosphonates, denosumab, and/or endocrine therapy administered during the study are eligible and may continue throughout duration of study
• Patients must be at least 28 days post systemic steroids prior to enrollment
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status score of =< 2
• White blood cell (WBC) >= 3000/mm^3
• Hemoglobin (Hgb) >= 10 g/dl
• Lymphocyte count >= 800/mm^3
• Platelet count >= 75,000/mm^3
• Serum creatinine =< 2.0 mg/dl or creatinine clearance > 60 ml/min
• Total bilirubin =< 1.5 mg/dl
• Aspartate aminotransferase (AST)/Serum glutamic oxaloacetic transaminase (SGOT) =< 2 times upper limit of normal (ULN)
• 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
• The effects of WOKVAC on the developing human fetus are unknown. For this reason, patients who are having sex that can lead to pregnancy must agree to use adequate contraception (hormonal, barrier method of birth control, or abstinence) for the duration of study participation; should a woman become pregnant while participating in the study, she should inform her study doctor immediately and will not receive any more study treatment
• Left ventricular ejection fraction (LVEF) results must be >= lower limit of normal (LLN) for institution performing based on results from the multi-gated acquisition (MUGA) or echocardiogram (ECHO) done at baseline
• Willing to not undergo any elective surgical procedure with general anesthesia or conscious sedation through the 1 month post-vaccination visit
• Ability to understand and the 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
• Patients may not be receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to WOKVAC
• Patients with any contraindication or known hypersensitivity to receiving sargramostim (recombinant human granulocyte macrophage colony stimulating factor [rhuGM-CSF]) or other yeast based products
• Pregnant women are excluded from this study because WOKVAC is a vaccine agent with unknown potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with WOKVAC breastfeeding should be discontinued if the mother is treated with this vaccine
• History of diabetes
• Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C
• History of autoimmunity that has not been controlled with treatment in the last 12 months

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Mary (Nora) Disis

Professor, Clinical Research Division

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kari Wisinski

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Countries

United States

References

Disis ML, Gad E, Herendeen DR, Lai VP, Park KH, Cecil DL, O'Meara MM, Treuting PM, Lubet RA. A multiantigen vaccine targeting neu, IGFBP-2, and IGF-IR prevents tumor progression in mice with preinvasive breast disease. Cancer Prev Res (Phila). 2013 Dec;6(12):1273-82. doi: 10.1158/1940-6207.CAPR-13-0182. Epub 2013 Oct 23.

Reference Type: RESULT

PMID: 24154719 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2016-00581

Identifier Type: REGISTRY

Identifier Source: secondary_id

UW14090

Identifier Type: -

Identifier Source: secondary_id

N01-CN-2012-00033

Identifier Type: -

Identifier Source: secondary_id

UWI4090

Identifier Type: OTHER

Identifier Source: secondary_id

UWI2014-03-01

Identifier Type: OTHER

Identifier Source: secondary_id

N01CN00033

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA014520

Identifier Type: NIH

Identifier Source: secondary_id

View Link

RG1716053

Identifier Type: OTHER

Identifier Source: secondary_id

9626

Identifier Type: -

Identifier Source: org_study_id

NCT03156309

Identifier Type: -

Identifier Source: nct_alias