Clinical Trials /

Neoantigen DNA Vaccine in Pancreatic Cancer Patients Following Surgical Resection and Adjuvant Chemotherapy

NCT03122106

Description:

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.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Neoantigen DNA Vaccine in Pancreatic Cancer Patients Following Surgical Resection and Adjuvant Chemotherapy
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 201708105
  • SECONDARY ID: P50CA196510-01A1
  • NCT ID: NCT03122106

Conditions

  • Pancreatic Cancer
  • Pancreas Cancer
  • Cancer of the Pancreas

Interventions

DrugSynonymsArms
Personalized neoantigen DNA vaccinePersonalized neoantigen DNA vaccine

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Personalized neoantigen DNA vaccineExperimentalVaccines will be weeks 1, 5, 9, 13, 17, and 21. Vaccines will occur within +/- 1 week with at least 3 weeks between vaccines. All study injections will be given intramuscularly using TDS-IM system. At each vaccination time point, patients will receive 2 injections of the neoantigen DNA vaccine, 1 injection into each deltoid or lateralis. Minimum observation of 30 minutes. Vital signs will be taken at 30-45 minutes post-immunization. The injection sites will be inspected for evidence of local reaction. Follow up on subject well-being will be performed by telephone on the 1st or 2nd day following each injection. -Post-vaccination follow-up visits are at Week 25 ± 7 days and Week 77 ± 14 days. Additional follow-up visits or telephone contact will be scheduled at Week 129 and annually thereafter if the patient is alive and available for follow-up. At intervals throughout the study (both before and after vaccination) subjects will have blood drawn for immunologic assays.
  • Personalized neoantigen DNA vaccine

Eligibility Criteria

        A patient will be eligible for evaluation and sequencing of tissue for vaccine development
        only if ALL of the following criteria apply:

        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

               -  total bilirubin ≤2.5 X institutional upper limit of normal (ULN)

               -  AST/ALT≤ 2.5 X institutional upper limit of normal

               -  creatinine ≤1.5 X institutional upper limit of normal

          -  International Normalized Ratio (INR) and activated partial thromboplastin time (PTT) <
             1.5 x ULN provided the patient is not on anticoagulation therapy.

          -  Patients who have had a stent placed for biliary obstruction can be included in the
             study provided serum bilirubin at time of enrollment is within protocol limits.

          -  Women of child-bearing potential and men 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. Should a woman become pregnant or suspect she is
             pregnant while participating in this study, she must inform her treating physician
             immediately.

          -  Able to understand and willing to sign an IRB approved written informed consent
             document.

        At eligibility recheck prior to vaccination, the above criteria must be met plus:

          -  Completed adjuvant chemotherapy:

               -  Initiation of adjuvant chemotherapy within 12 weeks of surgery

               -  Completion of at least 4 months of adjuvant chemotherapy with
                  gemcitabine/capecitabine or similar adjuvant chemotherapy at the discretion of
                  the patient's medical oncologist.

               -  Additional chemoradiation therapy as recommended by the patient's medical
                  oncologist.

               -  Reimaging within 4 weeks of last dose of chemotherapy demonstrates no evidence of
                  recurrent disease and CA 19-9 is less than 92.5 u/mL

               -  Dose modifications and/or delays in adjuvant chemotherapy is at the discretion of
                  the treating physician

          -  Neoadjuvant chemotherapy is exclusionary.

          -  There is a 1 week washout prior to Day 1 of vaccine for patients on daily systemic
             steroids at doses exceeding 10 mg prednisone.

        Exclusion Criteria:

          -  Evidence of neuroendocrine tumor, duodenal adenocarcinoma, or ampullary
             adenocarcinoma.

          -  Received neoadjuvant chemotherapy

          -  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.

          -  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.

          -  Any chronic or active neurologic disorder, including seizures and epilepsy, excluding
             a single febrile seizure as a child.

          -  Current use of any electronic stimulation device, such as cardiac demand pacemakers,
             automatic implantable cardiac defibrillator, nerve stimulators, or deep brain
             stimulators.

          -  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, Sjögren'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. In the case of asthma or chronic
             obstructive pulmonary disease taking inhaled corticosteroids that does not require
             daily systemic corticosteroids is acceptable. Additionally, local acting steroids
             (topical, inhaled, or intraarticular) will be allowed. Patients on intermittent or
             short course steroids will be allow if the dose does not exceed 4 mg of dexamethasone
             (or equivalent) per day for > 7 consecutive days. Any patients receiving steroids
             should be discussed with the PI to determine if eligible.

          -  Pregnant and/or breastfeeding.

          -  Known HIV-positive status. These patients are ineligible because of the potential
             inability to generate an immune response to vaccines.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety of neoantigen DNA vaccine as measured by the number of subjects experiencing each type of adverse event
Time Frame:Through week 24
Safety Issue:
Description:-Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0

Secondary Outcome Measures

Measure:Immunogenicity of the neoantigen DNA vaccine as measured by the frequency of antigen -specific T cells using ELISPOT analysis
Time Frame:Through week 77
Safety Issue:
Description:-The frequency of antigen-specific T cells at each time will be summarized using means, standard deviations and medians, and the change over time will also be compared using two-ANOVA for repeated measurement data or Friedman rank-sum test as appropriate.
Measure:Immunogenicity of the neoantigen DNA vaccine as measured by the phenotypic characteristics of antigen-specific T cells using multiparametric flow cytometry
Time Frame:Through week 77
Safety Issue:
Description:-Responses will be considered positive if the number of T cells after vaccination is greater than two standard deviations above the mean before vaccination. The frequency of positive responses at each time point will be assessed and binomial response rates with 95% confidence interval estimates will be presented.
Measure:Immunogenicity of the neoantigen DNA vaccine as measured by the functional characteristics of antigen-specific T cells using multiparametric flow cytometry
Time Frame:Through week 77
Safety Issue:
Description:-Responses will be considered positive if the number of T cells after vaccination is greater than two standard deviations above the mean before vaccination. The frequency of positive responses at each time point will be assessed and binomial response rates with 95% confidence interval estimates will be presented.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Washington University School of Medicine

Last Updated

September 19, 2019