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

Pancreatic Cancer Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT03956056
• Other study ID #: 201908124
• Secondary ID: P50CA196510-03
• Status: Terminated
• Phase: Phase 1
• Start date: February 13, 2020
• Est. completion date: July 6, 2023

Study information

• Verified date: July 2023
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: July 6, 2023
• Est. primary completion date: July 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cancer of the Pancreas
• Pancreas Cancer
• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Biological:
• Neoantigen Peptide Vaccine
• Each pool of vaccine study drug + poly IC:LC will be administered to one of the four limbs (A - Right Arm, B - Left Arm, C - Right Leg, D - Left Leg) by subcutaneous (SC) injection.

Drug:
• Poly ICLC
• Each pool of vaccine study drug + poly IC:LC will be administered to one of the four limbs (A - Right Arm, B - Left Arm, C - Right Leg, D - Left Leg) by subcutaneous (SC) injection.

Procedure:
• Blood for immune monitoring
-Baseline, day 1, day 22, day 50, day 78, week 25, and week 73

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (3)

Lead Sponsor	Collaborator
Washington University School of Medicine	National Cancer Institute (NCI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of Neoantigen Peptide Vaccine as Measured by the Number of Serious Adverse Events	-Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0.	Through 30 days following completion of treatment (median follow-up of 107 days, full range of 88-157 days)
Secondary	Immunogenicity of the Neoantigen Peptide Vaccine as Measured by ELISPOT Analysis	-The ELISPOT analysis is based on measuring the frequencies of IFN-? producing T cells in response to polyepitope antigen	Baseline through week 52
Secondary	Immunogenicity of the Neoantigen Peptide Vaccine as Measured by Multiparametric Flow Cytometry	-The multiparametric flow cytometry assesses phenotypic as well as functional characteristics of epitope-specific T cells.	Baseline through week 52

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine