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

NCT03122106 | Terminated Phase 1 Results DMC FDA Drug FDA Device

• 2 other identifiers: 201708105P50CA196510-01A1
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Pancreatic Cancer; Pancreas Cancer; Cancer of the Pancreas

Outcome Measures

Primary Outcomes (1)

• Safety of Neoantigen DNA Vaccine as Measured by the Number of Subjects Experiencing Each Type of Treatment-related Adverse Event

  * Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 * Related indicates possibly, probably, or definitely related to the study treatment

  Through week 24

Secondary Outcomes (2)

• Immunogenicity of the Neoantigen DNA Vaccine as Measured by ELISPOT Analysis

  Through week 77

• Immunogenicity of the Neoantigen DNA Vaccine as Measured by Multiparametric Flow Cytometry

  Through week 77

Study Arms (1)

Personalized neoantigen DNA vaccine

EXPERIMENTAL

* Vaccines will be weeks 1, 5, 9, 13, 17, and 21. Vaccines will occur within +/- 1 week with at least 3 weeks between vaccines. All study injections will be given intramuscularly using TDS-IM system. At each vaccination time point, patients will receive 2 injections of the neoantigen DNA vaccine, 1 injection into each deltoid or lateralis. * Minimum observation of 30 minutes. Vital signs will be taken at 30-45 minutes post-immunization. The injection sites will be inspected for evidence of local reaction. Follow up on subject well-being will be performed by telephone on the 1st or 2nd day following each injection. -Post-vaccination follow-up visits are at Week 25 ± 7 days and Week 77 ± 14 days. Additional follow-up visits or telephone contact will be scheduled at Week 129 and annually thereafter if the patient is alive and available for follow-up. * At intervals throughout the study (both before and after vaccination) subjects will have blood drawn for immunologic assays.

Biological: Personalized neoantigen DNA vaccine; Device: TDS-IM Electrode Array System; Procedure: Peripheral blood draws

Interventions

Personalized neoantigen DNA vaccine BIOLOGICAL

-Personalized polyepitope inserts integrating the prioritized neoantigens and mesothelin epitopes will be designed and then synthesized and cloned into the pING parent vector

Personalized neoantigen DNA vaccine

TDS-IM Electrode Array System DEVICE

-Ichor Medical Systems

Personalized neoantigen DNA vaccine

Peripheral blood draws PROCEDURE

-Enrollment, mid adjuvant chemotherapy, end of chemotherapy, week 1, week 5, week 9, week 13, week 17, week 21, week 25, and week 77

Personalized neoantigen DNA 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.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Normal bone marrow and organ function as defined below:
• white blood cells (WBC) ≥3,000/μL
• absolute neutrophil count ≥1,500/μL
• platelets ≥100,000/μL
• total bilirubin ≤2.5 X institutional upper limit of normal (ULN)
• AST/ALT≤ 2.5 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 or carcinoma in situ of the cervix.
• Receiving any other investigational agents, or has received an investigational agent within the last 30 days.
• 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
• History of syncopal or vasovagal episode as determined by medical record and history in the 12 month period prior to first vaccination administration.
• Individuals in whom a skinfold measurement of the cutaneous and subcutaneous tissue for eligible injection sites (left and right medial deltoid region) exceeds 40 mm.
• Individuals in whom the ability to observe possible local reactions at the eligible injection sites (deltoid region) is, in the opinion of the investigator, unacceptably obscured due to a physical condition or permanent body art.
• Therapeutic or traumatic metal implant in the skin or muscle of either deltoid region.
• Any chronic or active neurologic disorder, including seizures and epilepsy, excluding a single febrile seizure as a child.
• Current use of any electronic stimulation device, such as cardiac demand pacemakers, automatic implantable cardiac defibrillator, nerve stimulators, or deep brain stimulators.
• 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.

Sponsors & Collaborators

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

Study Sites (2)

Johns Hopkins School of Medicine

Baltimore, Maryland, 21231, United States

Location

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

Condition Hierarchy (Ancestors)

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

Results Point of Contact

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

gillandersw@wustl.edu

314-747-0072

Study Officials

• William Gillanders, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Daniel Laheru, M.D.

  Johns Hopkins 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: April 17, 2017
• First Posted: April 20, 2017
• Study Start: January 5, 2018
• Primary Completion: September 3, 2021
• Study Completion: August 13, 2022
• Last Updated: October 10, 2023
• Results First Posted: October 4, 2022

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)