A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of a Personalized Polyepitope DNA Vaccine Strategy in Breast Cancer Patients With Persistent Triple-Negative Disease Following Neoadjuvant Chemotherapy

Washington University School of Medicine1 site in 1 country18 target enrollmentJune 17, 2015

ConditionsTriple Negative Breast Cancer Triple-Negative Breast Cancer Triple Negative Breast Neoplasms

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Triple Negative Breast Cancer
Sponsor: Washington University School of Medicine
Enrollment: 18
Locations: 1
Primary Endpoint: Safety of the personalized polyepitope DNA vaccine strategy, measured by both clinical observation and laboratory evaluation
Status: Completed
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This is a phase 1 open-label study to evaluate the safety and immunogenicity of a personalized polyepitope DNA vaccine strategy. The personalized polyepitope DNA vaccines will be formulated as naked plasmid DNA vaccines. The hypothesis of this study is that personalized polyepitope DNA vaccines will be safe for human administration and capable of generating measurable CD8 T cell responses to mutant tumor-specific antigens.

Registry

clinicaltrials.gov

Start Date

June 17, 2015

End Date

March 12, 2020

Last Updated

5 years ago

Study Type

Interventional

Study Design

Single Group

Sex

Female

Investigators

Sponsor

Washington University School of Medicine

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologically confirmed diagnosis of invasive breast cancer.
•ER and PR less than Allred score of 3 or less than 1% positive staining cells in the invasive component of the tumor. Patients not meeting this pathology criteria, but have been clinically treated as having TNBC, can be enrolled at PI discretion.
•HER2 negative by FISH or IHC staining 0 or 1+.
•Consented for genome sequencing and dbGAP-based data sharing and has provided or will provide germline and tumor DNA samples of adequate quality for sequencing. Fresh tissue is preferred (from biopsy at the time of port placement) but archival tissue is allowed
•Clinical stage T1c-T4c, any N, M0 primary tumor by AJCC 7th edition clinical staging prior to neoadjuvant chemotherapy, with residual invasive breast cancer after neoadjuvant therapy. If the patient has invasive cancer in the contralateral breast, she is not eligible for this study.
•At least 18 years of age. Eastern Cooperative Oncology Group (ECOG) performance status ≤2
•Adequate organ and marrow function no more than 14 days prior to registration as defined below:
•WBC ≥ 3,000/μL
•absolute neutrophil count ≥1,500/μL
•platelets ≥ 100,000/μL

Exclusion Criteria

•Evidence of progressive breast cancer within the last 30 days.
•Received chemotherapy, radiotherapy, or biologic therapy within the last 30 days (neoadjuvant chemotherapy excluded).
•Experiencing any clinically significant adverse events above Grade 1 (according to CTCAE 4.0) due to agents administered more than 30 days earlier. However, patients with Grade 2 Alopecia will be considered eligible.
•Receiving any other investigational agent(s) or has received an investigational agent within the last 30 days.
•Known metastatic disease.
•Invasive cancer in the contralateral breast.
•Known allergy, or history of serious adverse reaction to vaccines such as anaphylaxis, hives, or respiratory difficulty.
•Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (including sinus bradycardia), or psychiatric illness/social situation that would limit compliance with study requirements.
•Prior or currently active autoimmune disease requiring management with immunosuppression. This includes inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, sarcoidosis, or other rheumatologic disease or any other medical condition or use of medication (e.g., corticosteroids) which might make it difficult for the patient to complete the full course of treatments or to generate an immune response to vaccines. Asthma or chronic obstructive pulmonary disease that does not require daily systemic corticosteroids is acceptable. Any patients receiving steroids should be discussed with the PI to determine if eligible.
•Pregnant or breastfeeding. A negative serum pregnancy test is required no more than 7 days before study entry.

Outcomes

Primary Outcomes

Safety of the personalized polyepitope DNA vaccine strategy, measured by both clinical observation and laboratory evaluation

Time Frame: 52 weeks

Assessment of plasmid DNA safety will include both clinical observation and laboratory evaluation. Safety will be closely monitored after injection with eight or more clinical and laboratory assessments in the first 24 weeks of the trial. The following parameters will be assessed following vaccination: 1. Local signs and symptoms 2. Systemic signs and symptoms 3. Laboratory evaluations, including blood counts and serum chemistries 4. Adverse, and serious adverse events

Secondary Outcomes

Immunogenicity of the personalized polyepitope DNA vaccine strategy, measured by ELISPOT analysis, a surrogate for CD8 T cell function, and multiparametric flow cytometry(52 weeks)