- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02348320
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 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
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Missouri
-
Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
- 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.
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.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Personalized polyepitope DNA vaccine
Participants 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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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:
|
52 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Immunogenicity of the personalized polyepitope DNA vaccine strategy, measured by ELISPOT analysis, a surrogate for CD8 T cell function, and multiparametric flow cytometry
Time Frame: 52 weeks
|
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.
|
52 weeks
|
Collaborators and Investigators
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 201505074
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Triple Negative Breast Cancer
-
Peregrine PharmaceuticalsWithdrawnBreast Cancer | Triple Negative Breast Cancer | Triple Negative Breast Neoplasms | Triple-Negative Breast Cancer | Triple-Negative Breast Neoplasm | ER-Negative PR-Negative HER2-Negative Breast Neoplasms | ER-Negative PR-Negative HER2-Negative Breast Cancer
-
Swiss Group for Clinical Cancer ResearchNot yet recruitingTriple-negative Breast Cancer | TNBC - Triple-Negative Breast CancerSwitzerland
-
G1 Therapeutics, Inc.TerminatedBreast Cancer | Breast Neoplasm | Triple-Negative Breast Cancer | Triple-Negative Breast NeoplasmsUnited States, Bulgaria, Croatia, Slovenia, Serbia, Belgium, North Macedonia, Slovakia
-
AkesoRecruitingMetastatic Triple-negative Breast Cancer | Locally Advanced Triple-negative Breast CancerChina
-
Washington University School of MedicineNational Cancer Institute (NCI); National Institutes of Health (NIH); MedImmune...TerminatedTriple Negative Breast Cancer | Triple Negative Breast Neoplasms | TNBC - Triple-Negative Breast Cancer | Triple-negative Breast CarcinomaUnited States
-
CelgeneCompletedBreast Cancer | Metastatic Breast Cancer | Stage IV Breast Cancer | Triple-negative Breast Cancer | Recurrent Breast Cancer | Breast Tumor | Cancer of the Breast | Triple-negative Metastatic Breast Cancer | Estrogen Receptor- Negative Breast Cancer | HER2- Negative Breast Cancer | Progesterone Receptor- Negative...United States, United Kingdom, Italy, Germany, Spain, Canada, Portugal, Australia, Austria, Greece, Brazil, France
-
Melinda TelliPfizer; BioMarin PharmaceuticalCompletedAdvanced Breast Cancer | HER2/Neu Negative | Triple-Negative Breast CancerUnited States
-
Fudan UniversityNot yet recruitingTriple-negative Breast Cancer
-
UNICANCERSOLTI Breast Cancer Research Group; Vall d'Hebron Institute of Oncology; MSD...Not yet recruitingTriple-negative Breast Cancer
-
Shanghai Jiao Tong University School of MedicineCSPC Ouyi Pharmaceutical Co., Ltd.; Innovent Biologics, Inc.Not yet recruiting
Clinical Trials on Personalized polyepitope DNA vaccine
-
University of WashingtonUnited States Department of Defense; Breast Cancer AllianceActive, not recruitingStage IV Breast Cancer | Recurrent Breast Carcinoma | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IIIC Breast Cancer | Stage III Breast Cancer | HER2 Negative Breast CarcinomaUnited States
-
Washington University School of MedicineChildren's Discovery InstituteNot yet recruitingNeoepitope-based Personalized DNA Vaccine Approach in Pediatric Patients With Recurrent Brain TumorsPediatric Recurrent Brain TumorUnited States
-
Washington University School of MedicineNational Cancer Institute (NCI)TerminatedPancreatic Cancer | Pancreas Cancer | Cancer of the PancreasUnited States
-
University of WashingtonNational Cancer Institute (NCI); University of Wisconsin, MadisonRecruitingAnatomic 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... and other conditionsUnited States
-
Washington University School of MedicineIncyte Corporation; PapiVax Biotech, Inc.RecruitingUnmethylated GlioblastomaUnited States
-
Institut de Cancérologie de LorraineRecruiting
-
University of WashingtonUnited States Department of DefenseRecruitingLung Non-Small Cell Carcinoma | Stage IV Lung Cancer AJCC v8United States
-
National Institute of Allergy and Infectious Diseases...The Emmes Company, LLCCompleted
-
Xuanwu Hospital, BeijingBeijing Neoantigen Biotechnology CompanyRecruitingMalignant Glioma | Recurrent GliomaChina
-
Guangdong 999 Brain HospitalJinan University Guangzhou; Beijing Tricision Biotherapeutics Inc; Trinomab Biotech...CompletedBrain Cancer | Neoplasm MetastasesChina