AzTrials
AzTrials

Triple Negative Breast CancerPhase 1NCT02348320

Safety and Immunogenicity of a Personalized Polyepitope DNA Vaccine Strategy in Breast Cancer Patients With Persistent Triple-Negative Disease Following Neoadjuvant Chemotherapy

A Phase 1 study testing Personalized polyepitope DNA vaccine in people with Triple Negative Breast Cancer and Triple-Negative Breast Cancer, run by Washington University School of Medicine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Personalized polyepitope DNA vaccine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
17 Jun 2015to 12 Mar 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 15Show fewer
  • 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
  • total bilirubin ≤ 2.5 X institutional upper limit of normal
  • AST/ALT ≤ 2.5 X institutional upper limit of normal
  • creatinine ≤ 1.5 X institutional upper limit of normal
  • Women of reproductive potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
  • Able to understand and willing to sign an IRB-approved written informed consent document.

Who cannot join

  • 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.
Show all 21Show fewer
  • 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.
  • The patient with a previous history of non-breast malignancy is eligible for this study only if the patient meets the following criteria for a cancer survivor. A cancer survivor is eligible provided the following criteria are met: (1) patient has undergone potentially curative therapy for all prior malignancies, (2) patients have been considered disease free for at least 1 year (with the exception of basal cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix).
  • Patient must have no active major medical or psychosocial problems that could be complicated by study participation.
  • Known HIV-positive status. These patients are ineligible because of the potential inability to generate an immune response to vaccines.
  • Subjects with a strong likelihood of non-adherence such as difficulties in adhering to follow-up schedule due to geographic distance from the Siteman Cancer Center should not knowingly be registered.
  • Individuals in whom a skinfold measurement of the cutaneous and subcutaneous tissue for eligible injection sites (left and right medial deltoid region) exceeds 40 mm.
  • Individuals in whom the ability to observe possible local reactions at the eligible injection sites (deltoid region) is, in the opinion of the investigator, unacceptably obscured due to a physical condition or permanent body art.
  • Therapeutic or traumatic metal implant in the skin or muscle of either deltoid region.
  • Acute or chronic, clinically significant hematologic, pulmonary, cardiovascular, or hepatic or renal functional abnormality as determined by the investigator based on medical history, physical examination, EKG, and/or laboratory screening test
  • Any chronic or active neurologic disorder, including seizures and epilepsy, excluding a single febrile seizure as a child
  • Syncopal episode within 12 months of screening
  • Current use of any electronic stimulation device, such as cardiac demand pacemakers, automatic implantable cardiac defibrillator, nerve stimulators, or deep brain stimulators.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: 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

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.

Being tested
Personalized polyepitope DNA vaccine
Medical subject headings
Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Personalized polyepitope DNA vaccineBiological

Study groups in NCT02348320
Study groupRoleWhat they receive
Personalized polyepitope DNA vaccineExperimentalParticipants will be treated by electroporation with 4 mg of a personalized polyepitope DNA vaccine at Day 1, Day 29 (+/1- 7 days), and Day 57 (+/- 7 days) with at least 21 days between injection days. Each DNA vaccination with be 4 mg vaccine administered intramuscularly using a TriGrid electroporation device.
Receives: Biological: Personalized polyepitope DNA vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    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

    Measured: 52 weeks

Secondary outcomes (1)

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

    Immunogenicity will be measured by ELISPOT analysis, a surrogate for CD8 T cell function, and multiparametric flow cytometry. In both assays the quantity and quality of antigen-specific CD8 T cells is determined; the ELISPOT analysis is based on measuring the frequencies of IFN-γ producing T cells in response to polyepitope antigen, whereas the multiparametric flow cytometry assesses phenotypic as well as functional characteristics of epitope-specific CD8 T cells. In the proposed study, blood samples will be collected at multiple time points (n=8) and PBMC isolated and cryopreserved. Upon completion of the vaccination protocol, all samples will be analyzed simultaneously in order to minimize assay-to-assay variation.

    Measured: 52 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jan 2015 (estimated)
  2. Study start17 Jun 2015
  3. Primary completion12 Mar 2020
  4. Study completion12 Mar 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02348320
Sponsor's protocol ID
201505074
Status last verified
Jun 2019
First submitted
21 Jan 2015
Last updated
1 Jul 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Zhang X, Goedegebuure SP, Chen MY, Mishra R, Zhang F, Yu YY, Singhal K, Li L, Gao F, Myers NB, Vickery T, Hundal J, McLellan MD, Sturmoski MA, Kim SW, Chen I, Davidson JT 4th, Sankpal NV, Myles S, Suresh R, Ma CX, Foluso A, Wang-Gillam A, Davies S, Hagemann IS, Mardis ER, Griffith O, Griffith M, Miller CA, Hansen TH, Fleming TP, Schreiber RD, Gillanders WE. Neoantigen DNA vaccines are safe, feasible, and induce neoantigen-specific immune responses in triple-negative breast cancer patients. Genome Med. 2024 Nov 14;16(1):131. doi: 10.1186/s13073-024-01388-3.

    PubMed 39538331

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Personalized polyepitope DNA vaccine in people with Triple Negative Breast Cancer and Triple-Negative Breast Cancer, run by Washington University School of Medicine at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of the personalized polyepitope DNA vaccine strategy, measured by both clinical observation and laboratory evaluation (time frame: 52 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02348320, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in