Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03956056
Recruitment Status : Recruiting
First Posted : May 20, 2019
Last Update Posted : March 10, 2020
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Washington University School of Medicine

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.

Condition or disease Intervention/treatment Phase
Pancreas Cancer Pancreatic Cancer Cancer of the Pancreas Biological: Neoantigen Peptide Vaccine Drug: Poly ICLC Procedure: Blood for immune monitoring Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 13, 2020
Estimated Primary Completion Date : August 31, 2022
Estimated Study Completion Date : July 31, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Neoantigen Peptide Vaccine
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
• 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.
Other Names:
  • Poly-ICLC
  • Hiltonol

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




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


Secondary Outcome Measures :
  1. Immunogenicity of the neoantigen peptide vaccine as measured by ELISPOT analysis [ Time Frame: Baseline through week 52 ]
    -The ELISPOT analysis is based on measuring the frequencies of IFN-γ producing T cells in response to polyepitope antigen

  2. Immunogenicity of the neoantigen peptide vaccine as measured by multiparametric flow cytometry [ Time Frame: Baseline through week 52 ]
    -The multiparametric flow cytometry assesses phenotypic as well as functional characteristics of epitope-specific T cells.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03956056


Contacts
Layout table for location contacts
Contact: William E Gillanders, M.D. 314-747-0072 gillanders@wustl.edu

Locations
Layout table for location information
United States, Maryland
Johns Hopkins School of Medicine Not yet recruiting
Baltimore, Maryland, United States, 21231
Contact: Daniel A Laheru, M.D.    410-955-8974    laherda@jhmi.edu   
Principal Investigator: Daniel A Laheru, M.D.         
Sub-Investigator: Elizabeth Jaffee, M.D.         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: William E Gillanders, M.D.    314-747-0072    gillanders@wustl.edu   
Principal Investigator: William E Gillanders, M.D.         
Sub-Investigator: Robert D Schreiber, Ph.D.         
Sub-Investigator: Christopher A Miller, Ph.D.         
Sub-Investigator: Feng Gao, Ph.D.         
Sub-Investigator: S. Peter Goedegebuure, Ph.D.         
Sub-Investigator: William Hawkins, M.D.         
Sub-Investigator: Kian H Lim, M.D.         
Sub-Investigator: Marianna Ruzinova, M.D., Ph.D.         
Sub-Investigator: C. Alston James, M.D.         
Sponsors and Collaborators
Washington University School of Medicine
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: William E Gillanders, M.D. Washington University School of Medicine
Additional Information:
Layout table for additonal information
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT03956056    
Other Study ID Numbers: 201908124
P50CA196510-03 ( U.S. NIH Grant/Contract )
First Posted: May 20, 2019    Key Record Dates
Last Update Posted: March 10, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Poly I-C
Carboxymethylcellulose Sodium
Poly ICLC
Interferon Inducers
Immunologic Factors
Physiological Effects of Drugs
Laxatives
Gastrointestinal Agents
Antiviral Agents
Anti-Infective Agents