Personalized DNA Vaccine in Treating Patients with Pancreatic Cancer Who Have Undergone Surgery and Received Chemotherapy

Status: Active

Description

This phase I trial studies the side effects of a personalized deoxyribonucleic acid (DNA) vaccine in treating patients with pancreatic cancer who have undergone surgery and received chemotherapy. DNA is material that contains the information needed to produce many substances in the body. The personalized DNA vaccine is designed to target mutations specific to each patient's tumor that are discovered during genetic testing of the tumor before study procedures start. Injection of this personalized DNA vaccine may be a way to generate an immune response to kill tumor cells.

Eligibility 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 1 mm biopsies from the original formalin-fixed paraffin-embedded (FFPE) blocks
  • Life expectancy of > 12 months
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • White blood cells (WBC) >= 3,000/uL
  • Absolute neutrophil count >= 1,500/uL
  • Platelets >= 100,000/uL
  • Total bilirubin =< 2.5 X institutional upper limit of normal
  • Aspartate aminotransferase (AST)/alanine aminotransferase (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 upper limit of normal (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
  • 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 Institutional Review Board (IRB) approved written informed consent document
  • At eligibility recheck prior to vaccination, the above criteria must be met plus: * Completed adjuvant chemotherapy: ** Initiation of adjuvant chemotherapy within 12 weeks of surgery ** Completion of at least 4 months of adjuvant chemotherapy with gemcitabine/capecitabine or similar adjuvant chemotherapy at the discretion of the patient’s medical oncologist ** Additional chemoradiation therapy as recommended by the patient’s medical oncologist ** Reimaging within 4 weeks of last dose of chemotherapy demonstrates no evidence of recurrent disease and CA 19-9 is less than 92.5 u/mL ** Dose modifications and/or delays in adjuvant chemotherapy is at the discretion of the treating physician * Neoadjuvant chemotherapy is exclusionary * There is a 1 week washout prior to day 1 of vaccine for patients on daily systemic steroids at doses exceeding 10 mg prednisone

Exclusion Criteria

  • Evidence of neuroendocrine tumor, duodenal adenocarcinoma, or ampullary adenocarcinoma
  • Received neoadjuvant chemotherapy
  • 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, Sjogren’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 principal investigator (PI) to determine if eligible
  • Pregnant and/or breastfeeding
  • Known human immunodeficiency virus (HIV)-positive status

Locations & Contacts

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: Approved
Contact: Daniel A. Laheru
Phone: 410-955-8974
Email: laherda@jhmi.edu

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: Active
Contact: William E. Gillanders
Phone: 314-747-0072
Email: gillandersw@wustl.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To assess the safety and feasibility of the neoantigen DNA-based pancreatic cancer vaccine (neoantigen DNA vaccine) approach.

SECONDARY OBJECTIVES:

I. To assess the prevalence of antigen-specific T cells in the peripheral blood of patients pre- and post-vaccination as measured by flow cytometry and enzyme-linked immunosorbent spot assay (ELISPOT).

EXPLORATORY OBJECTIVES:

I. Measurement of immune response, including the phenotype and functional status of neoantigen-specific T cells as measured by time-of-flight mass spectrometry (CYTOF) analysis.

II. To assess clinical response as measured by disease-free survival and overall survival.

OUTLINE:

Patients receive neoantigen DNA-based pancreatic cancer vaccine intramuscularly (IM) via electroporation (EP) in both left and right shoulder (it may be necessary for injections to be in each thigh instead; locations may be rotated) during weeks 1, 5, 9, 13, 17, and 21 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 and 52 weeks and then every year thereafter.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Siteman Cancer Center at Washington University

Principal Investigator
William E. Gillanders

Trial IDs

Primary ID 201708105
Secondary IDs NCI-2017-01587
Clinicaltrials.gov ID NCT03122106