Clinical Trials /

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

NCT03956056

Description:

This is a phase 1 open-label study to evaluate the safety and immunogenicity of a neoantigen peptide vaccine strategy in pancreatic cancer patients following surgical resection and adjuvant chemotherapy. The neoantigen peptide vaccines will incorporate prioritized neoantigens and personalized mesothelin epitopes and will be co-administered with poly-ICLC. The hypothesis of this study is that neoantigen peptide vaccines will be safe and capable of generating measurable neoantigen-specific CD4 and CD8 T cell responses.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 201908124
  • SECONDARY ID: P50CA196510-03
  • NCT ID: NCT03956056

Conditions

  • Pancreas Cancer
  • Pancreatic Cancer
  • Cancer of the Pancreas

Interventions

DrugSynonymsArms
Neoantigen Peptide VaccineNeoantigen Peptide Vaccine
Poly ICLCPoly-ICLC, HiltonolNeoantigen Peptide Vaccine

Purpose

This is a phase 1 open-label study to evaluate the safety and immunogenicity of a neoantigen peptide vaccine strategy in pancreatic cancer patients following surgical resection and adjuvant chemotherapy. The neoantigen peptide vaccines will incorporate prioritized neoantigens and personalized mesothelin epitopes and will be co-administered with poly-ICLC. The hypothesis of this study is that neoantigen peptide vaccines will be safe and capable of generating measurable neoantigen-specific CD4 and CD8 T cell responses.

Trial Arms

NameTypeDescriptionInterventions
Neoantigen Peptide VaccineExperimentalThe schedule for vaccination will be Days 1, 4, 8, 15, and 22 (delays of up to 96 hours are allowed for each dose based on the adverse events experienced). Additional vaccinations will be given on Days 50 and 78 (+/- 2 weeks). The first vaccine dose may be administered following confirmation of disease-free status and within 90 days following date of repeat imaging. All study injections will be given subcutaneously and co-administered with poly-ICLC by a trained healthcare provider.
  • Neoantigen Peptide Vaccine
  • Poly ICLC

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.

          -  ECOG performance status ≤ 2

          -  Normal bone marrow and organ function as defined below:

               -  WBC>=3,000/μL

               -  absolute neutrophil count>=1,500/μL

               -  platelets>=100,000/μL

               -  total bilirubin≤1.5 X institutional upper limit of normal (subjects with
                  Gilbert's syndrome may be enrolled despite a total bilirubin level >1.5 mg/dL if
                  their conjugated bilirubin is <1.5 x ULN)

               -  AST≤ 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.

             9-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.

        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,
             carcinoma in situ of the cervix, or LCIS/DCIS of the breast

          -  Known allergy, or history of serious adverse reaction to vaccines or TLR agonists 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

          -  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 peptide vaccine as measured by the number of serious adverse events
Time Frame:Through week 24
Safety Issue:
Description:-Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0.

Secondary Outcome Measures

Measure:Immunogenicity of the neoantigen peptide vaccine as measured by ELISPOT analysis
Time Frame:Baseline through week 52
Safety Issue:
Description:-The ELISPOT analysis is based on measuring the frequencies of IFN-γ producing T cells in response to polyepitope antigen
Measure:Immunogenicity of the neoantigen peptide vaccine as measured by multiparametric flow cytometry
Time Frame:Baseline through week 52
Safety Issue:
Description:-The multiparametric flow cytometry assesses phenotypic as well as functional characteristics of epitope-specific T cells.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Washington University School of Medicine

Last Updated

October 22, 2019