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

NCT03956056 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: 201908124P50CA196510-03
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pancreas Cancer; Pancreatic Cancer; Cancer of the Pancreas

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Number of Participants With Immune Response as Measured by ELISPOT Analysis

  Baseline through week 52

• Number of Participants With Immune Response as Measured by Multiparametric Flow Cytometry (CD4)

  Baseline through week 52

• Number of Participants With Immune Response as Measured by Multiparametric Flow Cytometry (CD8)

  Baseline through week 52

Study Arms (1)

Neoantigen Peptide Vaccine

EXPERIMENTAL

The 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.

Biological: Neoantigen Peptide Vaccine; Drug: Poly ICLC; Procedure: Blood for immune monitoring

Interventions

Neoantigen Peptide Vaccine BIOLOGICAL

• 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.

Neoantigen Peptide Vaccine

Poly ICLC DRUG

• 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.

Also known as: Poly-ICLC, Hiltonol

Neoantigen Peptide Vaccine

Blood for immune monitoring PROCEDURE

-Baseline, day 1, day 22, day 50, day 78, week 25, and week 73

Neoantigen Peptide Vaccine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

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

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

poly ICLC; Blood Specimen Collection; Monitoring, Immunologic

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Immunologic Tests; Monitoring, Physiologic; Immunologic Techniques

Results Point of Contact

• Title: William Gillanders, M.D.
• Organization: Washington University School of Medicine

gillandersw@wustl.edu

314-747-0072

Study Officials

• William E Gillanders, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2019
• First Posted: May 20, 2019
• Study Start: February 13, 2020
• Primary Completion: July 21, 2022
• Study Completion: July 6, 2023
• Last Updated: July 17, 2024
• Results First Posted: May 31, 2023

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)