A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of a Neoantigen DNA Vaccine Strategy in Pancreatic Cancer Patients Following Surgical Resection and Adjuvant Chemotherapy
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Pancreatic Cancer
- Sponsor
- Washington University School of Medicine
- Enrollment
- 15
- Locations
- 2
- Primary Endpoint
- Safety of Neoantigen DNA Vaccine as Measured by the Number of Subjects Experiencing Each Type of Treatment-related Adverse Event
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a phase 1 open-label study to evaluate the safety and immunogenicity of a neoantigen DNA vaccine strategy in pancreatic cancer patients following surgical resection and adjuvant chemotherapy. The neoantigen DNA vaccines will incorporate prioritized neoantigens and personalized mesothelin epitopes and will be administered with an electroporation device. The hypothesis of this study is that neoantigen DNA vaccines will be safe and capable of generating measurable neoantigen-specific CD4 and CD8 T cell responses.
Detailed Description
-Subjects will be enrolled within 12 weeks of surgery and standard of care adjuvant chemotherapy will last approximately 12 weeks with an additional 12 weeks of standard of care adjuvant chemotherapy or adjuvant chemoradiation. The first vaccine may be administered following confirmation of disease-free status and within 60 days following date of repeat imaging. From time of enrollment to first vaccine could be up to 45 weeks.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma; mixed histology will be included as long as the predominant histology is adenocarcinoma.
- •Completed an R0 or R1 surgical resection as determined by pathology
- •Pathology review demonstrates tumor cellularity no less than 30% in quantities sufficient to obtain 6-8 1mm biopsies from the original FFPE blocks.
- •At least 18 years of age.
- •Life expectancy of \> 12 months.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- •Normal bone marrow and organ function as defined below:
- •white blood cells (WBC) ≥3,000/μL
- •absolute neutrophil count ≥1,500/μL
- •platelets ≥100,000/μL
Exclusion Criteria
- •Evidence of neuroendocrine tumor, duodenal adenocarcinoma, or ampullary adenocarcinoma.
- •Received neoadjuvant chemotherapy for their pancreatic adenocarcinoma
- •Evidence of disease recurrence or metastasis following surgical resection at any time prior to the first vaccination administration. Most patients will undergo restaging midway through adjuvant chemotherapy and at the completion of therapy; however, timing of imaging is at the discretion of the patient's medical oncologist.
- •History of other malignancy ≤ 3 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
- •Receiving any other investigational agents, or has received an investigational agent within the last 30 days.
- •Known allergy, or history of serious adverse reaction to vaccines such as anaphylaxis, hives, or respiratory difficulty.
- •Acute or chronic, clinically significant hematologic, pulmonary, cardiovascular, hepatic renal, and/or other functional abnormality that would jeopardize the health and safety of the participant as determined by the investigator based on medical history, physical examination, laboratory values, and/or diagnostic studies.
- •A psychiatric illness/social situations that would limit compliance with study requirements as determined by the investigator from the medical history, physical exam, and/or medical record
- •History of syncopal or vasovagal episode as determined by medical record and history in the 12 month period prior to first vaccination administration.
- •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.
Outcomes
Primary Outcomes
Safety of Neoantigen DNA Vaccine as Measured by the Number of Subjects Experiencing Each Type of Treatment-related Adverse Event
Time Frame: Through week 24
* Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 * Related indicates possibly, probably, or definitely related to the study treatment
Secondary Outcomes
- Immunogenicity of the Neoantigen DNA Vaccine as Measured by ELISPOT Analysis(Through week 77)
- Immunogenicity of the Neoantigen DNA Vaccine as Measured by Multiparametric Flow Cytometry(Through week 77)