Clinical trial NCT02780401: Vaccine Therapy in Preventing Cancer Recurrence in Patients With Non-Metastatic, Node Positive, HER2 Negative Breast Cancer That is in Remission
Official title: A Phase I Trial of the Safety and Immunogenicity of a DNA Plasmid Based Vaccine (WOKVAC) Encoding Epitopes Derived From Three Breast Cancer Antigens (IGFBP-2, HER2, and IGF-1R) in Patients With Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Keywords: Stage I
Stage II
Stage III
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: University of Wisconsin, Madison
First posted: 2016-05-23
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Number of Adverse Events Per Common Terminology Criteria for Adverse Events Version 4.0
timeFrame: Up to 9 months
Secondary outcomes:
measure: Assessment of IgG Antibodies
timeFrame: Up to 4 months
measure: Assessment of T Helper Th1:Th2 Ratio
timeFrame: Up to 9 months
measure: Assessment of the Immunogenicity of WOKVAC by Generation of IGFBP-2, HER2, and IGF-1R Specific Type 1 (Th1) T- Cells
timeFrame: Up to 24 weeks
measure: Level of Antigen Specific Central and Effector Memory Phenotypes (Persistent Memory T Cell Response)
timeFrame: Up to 6 months after the last vaccine
measure: Modulation of Myeloid Derived Suppressor Cell Levels
timeFrame: Up to 24 weeks
measure: Modulation of T Regulatory Cell Levels
timeFrame: Up to 24 weeks
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutch/University of Washington Cancer Consortium
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Kari Wisinski
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.