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Neoantigen Vaccines in Pancreatic Cancer in the Window Prior to Surgery

Primary Purpose

Pancreas Cancer, Pancreatic Cancer, Cancer of the Pancreas

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Optimized neoantigen synthetic long peptide vaccine
Poly-ICLC
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreas Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Step 0 Inclusion Criteria (A patient will be eligible for evaluation and sequencing of tissue for vaccine development only if ALL of the following criteria apply:)

  • Histologically or cytologically confirmed, newly diagnosed, treatment-naïve patients with localized or borderline resectable adenocarcinoma of the pancreas for whom neoadjuvant chemotherapy is considered appropriate; mixed histology will be included as long as the predominant histology is adenocarcinoma. Patients with clinical suspicion of pancreatic adenocarcinoma can be enrolled for pre-treatment biopsy, and must be histologically confirmed to have adenocarcinoma before being treated on study. Patients with squamous carcinoma or neuroendocrine tumor will be excluded.
  • Evaluable disease, in the opinion of the treating investigator or PI.
  • Tissue specimens available in sufficient quantity to allow for sequencing.
  • At least 18 years of age.
  • Life expectancy of > 12 months.
  • ECOG performance status ≤ 1
  • Adequate bone marrow and organ function as defined below:

    • WBC ≥ 1,500/μL
    • absolute neutrophil count ≥ 1,000/μL
    • platelets ≥ 50,000/μL
    • hemoglobin ≥ 8.0 g/dL
    • total bilirubin ≤ 5.0 X institutional upper limit of normal
    • AST/ALT ≤ 5.0 X institutional upper limit of normal
    • creatinine ≤2.5 X institutional upper limit of normal OR creatinine clearance ≥ 30 mL/min by Cockcroft-Gault for patients with creatinine levels above institutional normal
    • Note: labs can be repeated prior to chemo if needed.
    • Note: Patients who have had a stent placed for biliary obstruction and whose liver function is expected to improve may enroll provided serum bilirubin at time of enrollment is within the limits above.
  • International Normalized Ratio (INR) and activated partial thromboplastin time (PTT) < 2.0 x ULN provided the patient is not on anticoagulation therapy.
  • Women of childbearing potential and men must agree to use two forms of adequate contraception prior to study entry, for the duration of study participation, and for 3 months after completion of the study. 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.

Step 0 Exclusion Criteria (A patient will be eligible for evaluation and sequencing of tissue for vaccine development only if ALL of the following criteria apply:)

  • Evidence of predominantly neuroendocrine (defined by > 50% histology) tumor, pure neuroendocrine tumor, duodenal adenocarcinoma, or ampullary adenocarcinoma.
  • 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.
  • Receiving any other investigational agents, or planning to receive other investigational agents as part of neoadjuvant therapy.
  • 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
  • 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.
  • History of positive test for Hepatitis B virus surface antigen (HBsAg) and/or positive Hepatitis C antibody result with detectable hepatitis C virus (HCV) ribonucleic acid (RNA) indicating acute or chronic infection.

Step 1 Eligibility: At Step 1 eligibility confirmation prior to vaccination, the above criteria must be met plus:

  • Completed at least 4 months of neoadjuvant chemotherapy such as FOLFIRINOX, modified FOLFIRINOX, or gemcitabine + nab-paclitaxel. Dose modifications and/or delays in neoadjuvant chemotherapy may be made at the discretion of the treating physician
  • Reimaging within 4 weeks of last dose of chemotherapy demonstrates no evidence of progressive disease. Patients who progress on mFOLFIRINOX and transition to gemcitabine + nab-paclitaxel can remain on study at discretion of PI and treating MD provided they do not show progression following completion of chemotherapy. Patients who, in the opinion of the treating physician, require SBRT prior to surgery will receive vaccine after surgery regardless of randomization.

    **Patients who progress or recur following neoadjuvant chemotherapy or who are otherwise unable to complete a surgical resection, but who still meet other Step 1 criteria, may still be eligible for vaccine administration with documented treating physician and PI approval.

  • There is a 1 week washout prior to Day 1 of vaccine for patients on daily systemic steroids at doses exceeding 10 mg prednisone.
  • Must not be receiving or have received any other investigational agents within the last 30 days. Note that patients who are receiving or will be receiving adjuvant chemotherapy are permitted to continue on study and are considered eligible.
  • Patients may not have received a live vaccine within 30 days prior to the first day of treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist) are live attenuated vaccines and are not allowed.
  • Sufficient wound healing per the evaluation of the treating physician.
  • If a patient experiences disease progression or recurrence during neoadjuvant chemotherapy, or is otherwise unable to complete a surgical resection after sufficient progress has been made on the vaccine production, the participant may still receive treatment with the peptide vaccine. Eligibility for continued participation in these cases will be at the treating physician and PI's discretion.

Sites / Locations

  • Washington University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm 1: Vaccine given after neoadjuvant chemotherapy and surgery

Arm 2: Vaccine given after neoadjuvant chemotherapy but before surgery

Arm Description

The neoantigen peptide vaccine will be manufactured during neoadjuvant chemotherapy. Institutional standard of care chemotherapy will be given. Peptide and poly-ICLC will be administered intramuscularly on Days 1, 4, 8, 15, 22, 50, and 78 beginning approximately 1 month after surgery. Day 1 should begin approximately 1 month after surgery.

The neoantigen peptide vaccine will be manufactured during neoadjuvant chemotherapy. Institutional standard of care chemotherapy will be given. Peptide and poly-ICLC will be administered intramuscularly on Days 1, 4, 8, 15, and 22 during the chemotherapy holiday, and Days 50 and 78 post-operatively. Optimal timing for Day 1 is 1 week after end of chemotherapy, but Day 1 may be given up to 3 weeks after end of chemotherapy.

Outcomes

Primary Outcome Measures

Safety of neoantigen SLP vaccine as measured by number of subjects experiencing each type of adverse event
-Adverse events will be characterized according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (CTCAE).

Secondary Outcome Measures

Immunogenicity of neoantigen peptide vaccine as measured by the the number of neoantigen-specific T cells (only Arm 1 and Arm 2)
Immune monitoring will occur at baseline, at time of surgery, day 1, day 15, day 22, and day 78 for Arm 1. Optional monitoring at 1 and 2 years after last vaccine administration Immune monitoring will occur at baseline, day 1, day 15, day 22, at the time of surgery, and day 78 for Arm 2. Optional monitoring at 1 and 2 years after last vaccine administration.
Immunogenicity of neoantigen peptide vaccine as measured by the phenotype of neoantigen-specific T cells (only Arm 1 and Arm 2)
Immune monitoring will occur at baseline, at time of surgery, day 1, day 15, day 22, and day 78 for Arm 1. Optional monitoring at 1 and 2 years after last vaccine administration Immune monitoring will occur at baseline, day 1, day 15, day 22, at the time of surgery, and day 78 for Arm 2. Optional monitoring at 1 and 2 years after last vaccine administration.

Full Information

First Posted
October 27, 2021
Last Updated
June 28, 2023
Sponsor
Washington University School of Medicine
Collaborators
National Cancer Institute (NCI), Leidos, UNICO Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT05111353
Brief Title
Neoantigen Vaccines in Pancreatic Cancer in the Window Prior to Surgery
Official Title
Neoantigen Vaccines in Pancreatic Cancer in the Window Prior to Surgery
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 15, 2022 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
Collaborators
National Cancer Institute (NCI), Leidos, UNICO Foundation

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a randomized phase 1 clinical trial to evaluate the safety of an optimized neoantigen synthetic long peptide (SLP) vaccines in pancreatic cancer patients following neoadjuvant chemotherapy. The neoantigen SLP vaccines will incorporate prioritized neoantigens and will be co-administered with poly-ICLC. Patients will be randomized to one of two arms: Arm 1 (neoantigen vaccine following neoadjuvant chemotherapy and surgery) or Arm 2 (neoantigen vaccine following neoadjuvant chemotherapy in the window prior to surgery). Those who are ineligible for vaccine administration including those whose disease progresses or recurs during neoadjuvant chemo or who are otherwise unable to complete surgical resection but who had a personalized neoantigen vaccine manufactured, or significant progress has been made as determined by treating physician, are permitted to receive vaccine injections on study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreas Cancer, Pancreatic Cancer, Cancer of the Pancreas

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm 1: Vaccine given after neoadjuvant chemotherapy and surgery
Arm Type
Experimental
Arm Description
The neoantigen peptide vaccine will be manufactured during neoadjuvant chemotherapy. Institutional standard of care chemotherapy will be given. Peptide and poly-ICLC will be administered intramuscularly on Days 1, 4, 8, 15, 22, 50, and 78 beginning approximately 1 month after surgery. Day 1 should begin approximately 1 month after surgery.
Arm Title
Arm 2: Vaccine given after neoadjuvant chemotherapy but before surgery
Arm Type
Experimental
Arm Description
The neoantigen peptide vaccine will be manufactured during neoadjuvant chemotherapy. Institutional standard of care chemotherapy will be given. Peptide and poly-ICLC will be administered intramuscularly on Days 1, 4, 8, 15, and 22 during the chemotherapy holiday, and Days 50 and 78 post-operatively. Optimal timing for Day 1 is 1 week after end of chemotherapy, but Day 1 may be given up to 3 weeks after end of chemotherapy.
Intervention Type
Biological
Intervention Name(s)
Optimized neoantigen synthetic long peptide vaccine
Intervention Description
Neoantigen vaccines will be provided on a patient-specific basis
Intervention Type
Biological
Intervention Name(s)
Poly-ICLC
Other Intervention Name(s)
Hiltonol
Intervention Description
Poly-ICLC will be supplied by Oncovir, Inc.
Primary Outcome Measure Information:
Title
Safety of neoantigen SLP vaccine as measured by number of subjects experiencing each type of adverse event
Description
-Adverse events will be characterized according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (CTCAE).
Time Frame
Through 30 days after completion of last vaccination (estimated to be 108 days)
Secondary Outcome Measure Information:
Title
Immunogenicity of neoantigen peptide vaccine as measured by the the number of neoantigen-specific T cells (only Arm 1 and Arm 2)
Description
Immune monitoring will occur at baseline, at time of surgery, day 1, day 15, day 22, and day 78 for Arm 1. Optional monitoring at 1 and 2 years after last vaccine administration Immune monitoring will occur at baseline, day 1, day 15, day 22, at the time of surgery, and day 78 for Arm 2. Optional monitoring at 1 and 2 years after last vaccine administration.
Time Frame
Through approximately 2 years and 78 days
Title
Immunogenicity of neoantigen peptide vaccine as measured by the phenotype of neoantigen-specific T cells (only Arm 1 and Arm 2)
Description
Immune monitoring will occur at baseline, at time of surgery, day 1, day 15, day 22, and day 78 for Arm 1. Optional monitoring at 1 and 2 years after last vaccine administration Immune monitoring will occur at baseline, day 1, day 15, day 22, at the time of surgery, and day 78 for Arm 2. Optional monitoring at 1 and 2 years after last vaccine administration.
Time Frame
Through approximately 2 years and 78 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Step 0 Inclusion Criteria (A patient will be eligible for evaluation and sequencing of tissue for vaccine development only if ALL of the following criteria apply:) Histologically or cytologically confirmed, newly diagnosed, treatment-naïve patients with localized or borderline resectable adenocarcinoma of the pancreas for whom neoadjuvant chemotherapy is considered appropriate; mixed histology will be included as long as the predominant histology is adenocarcinoma. Patients with clinical suspicion of pancreatic adenocarcinoma can be enrolled for pre-treatment biopsy, and must be histologically confirmed to have adenocarcinoma before being treated on study. Patients with squamous carcinoma or neuroendocrine tumor will be excluded. Evaluable disease, in the opinion of the treating investigator or PI. Tissue specimens available in sufficient quantity to allow for sequencing. At least 18 years of age. Life expectancy of > 12 months. ECOG performance status ≤ 1 Adequate bone marrow and organ function as defined below: WBC ≥ 1,500/μL absolute neutrophil count ≥ 1,000/μL platelets ≥ 50,000/μL hemoglobin ≥ 8.0 g/dL total bilirubin ≤ 5.0 X institutional upper limit of normal AST/ALT ≤ 5.0 X institutional upper limit of normal creatinine ≤2.5 X institutional upper limit of normal OR creatinine clearance ≥ 30 mL/min by Cockcroft-Gault for patients with creatinine levels above institutional normal Note: labs can be repeated prior to chemo if needed. Note: Patients who have had a stent placed for biliary obstruction and whose liver function is expected to improve may enroll provided serum bilirubin at time of enrollment is within the limits above. International Normalized Ratio (INR) and activated partial thromboplastin time (PTT) < 2.0 x ULN provided the patient is not on anticoagulation therapy. Women of childbearing potential and men must agree to use two forms of adequate contraception prior to study entry, for the duration of study participation, and for 3 months after completion of the study. 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. Step 0 Exclusion Criteria (A patient will be eligible for evaluation and sequencing of tissue for vaccine development only if ALL of the following criteria apply:) Evidence of predominantly neuroendocrine (defined by > 50% histology) tumor, pure neuroendocrine tumor, duodenal adenocarcinoma, or ampullary adenocarcinoma. 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. Receiving any other investigational agents, or planning to receive other investigational agents as part of neoadjuvant therapy. 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 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. History of positive test for Hepatitis B virus surface antigen (HBsAg) and/or positive Hepatitis C antibody result with detectable hepatitis C virus (HCV) ribonucleic acid (RNA) indicating acute or chronic infection. Step 1 Eligibility: At Step 1 eligibility confirmation prior to vaccination, the above criteria must be met plus: Completed at least 4 months of neoadjuvant chemotherapy such as FOLFIRINOX, modified FOLFIRINOX, or gemcitabine + nab-paclitaxel. Dose modifications and/or delays in neoadjuvant chemotherapy may be made at the discretion of the treating physician Reimaging within 4 weeks of last dose of chemotherapy demonstrates no evidence of progressive disease. Patients who progress on mFOLFIRINOX and transition to gemcitabine + nab-paclitaxel can remain on study at discretion of PI and treating MD provided they do not show progression following completion of chemotherapy. Patients who, in the opinion of the treating physician, require SBRT prior to surgery will receive vaccine after surgery regardless of randomization. **Patients who progress or recur following neoadjuvant chemotherapy or who are otherwise unable to complete a surgical resection, but who still meet other Step 1 criteria, may still be eligible for vaccine administration with documented treating physician and PI approval. There is a 1 week washout prior to Day 1 of vaccine for patients on daily systemic steroids at doses exceeding 10 mg prednisone. Must not be receiving or have received any other investigational agents within the last 30 days. Note that patients who are receiving or will be receiving adjuvant chemotherapy are permitted to continue on study and are considered eligible. Patients may not have received a live vaccine within 30 days prior to the first day of treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist) are live attenuated vaccines and are not allowed. Sufficient wound healing per the evaluation of the treating physician. If a patient experiences disease progression or recurrence during neoadjuvant chemotherapy, or is otherwise unable to complete a surgical resection after sufficient progress has been made on the vaccine production, the participant may still receive treatment with the peptide vaccine. Eligibility for continued participation in these cases will be at the treating physician and PI's discretion.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
William E Gillanders, M.D.
Phone
314-747-0072
Email
gillandersw@wustl.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William E Gillanders, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
William E Gillanders, M.D.
Phone
314-747-0072
Email
gillandersw@wustl.edu
First Name & Middle Initial & Last Name & Degree
William E Gillanders, M.D.
First Name & Middle Initial & Last Name & Degree
Robert D Schreiber, Ph.D.
First Name & Middle Initial & Last Name & Degree
Malachi Griffith, Ph.D.
First Name & Middle Initial & Last Name & Degree
Feng Gao, M.D., Ph.D.
First Name & Middle Initial & Last Name & Degree
S. Peter Goedegebuure, Ph.D.
First Name & Middle Initial & Last Name & Degree
William Hawkins, M.D.
First Name & Middle Initial & Last Name & Degree
Kian H Lim, M.D.
First Name & Middle Initial & Last Name & Degree
Koushik Das, M.D.
First Name & Middle Initial & Last Name & Degree
Marianna Ruzinova, M.D., Ph.D.
First Name & Middle Initial & Last Name & Degree
Sherri Davies, Ph.D.

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Sequencing data will be submitted to the database of Genotypes and Phenotypes (dbGap) at the National Cancer Institute.
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Learn more about this trial

Neoantigen Vaccines in Pancreatic Cancer in the Window Prior to Surgery

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