Clinical Trials /

Neoepitope-based Personalized DNA Vaccine Approach in Pediatric Patients With Recurrent Brain Tumors

NCT03988283

Description:

The purpose of this research study is to learn about the safety and feasibility of giving a personalized DNA vaccine to people with brain tumors that have returned or have been resistant to treatment.

Related Conditions:
  • Brain Neoplasm
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Neoepitope-based Personalized DNA Vaccine Approach in Pediatric Patients With Recurrent Brain Tumors
  • Official Title: A Pilot Study to Assess the Safety, Feasibility, and Preliminary Efficacy of a Neoepitope-based Personalized DNA Vaccine Approach in Pediatric Patients With Recurrent Brain Tumors

Clinical Trial IDs

  • ORG STUDY ID: 19-x190
  • NCT ID: NCT03988283

Conditions

  • Pediatric Recurrent Brain Tumor

Interventions

DrugSynonymsArms
Personalized neoantigen DNA vaccinePersonalized neoantigen DNA vaccine

Purpose

The purpose of this research study is to learn about the safety and feasibility of giving a personalized DNA vaccine to people with brain tumors that have returned or have been resistant to treatment.

Trial Arms

NameTypeDescriptionInterventions
Personalized neoantigen DNA vaccineExperimentalPatients will receive the vaccine on a 28-day cycle. It will be given weekly (+/- 3 days) during Cycle 1 (i.e., C1D1, C1D8, C1D15, C1D22) as a priming phase followed by booster injections on Day 1 (+/- 7 days) of each subsequent cycle (i.e., C2D1, C3D1, etc.). Vaccine administration will continue indefinitely until development of intolerance or disease progression in the case of fatal high grade neoplasms. Otherwise, vaccination will continue until intolerance or one year for non-fatal tumors. Additionally, patients with non-fatal tumors who complete one year of vaccinations and have stable disease will be given the option of resuming vaccinations if they develop subsequent progression.
  • Personalized neoantigen DNA vaccine

Eligibility Criteria

        Inclusion Criteria:

          -  Any patient ≤ 39 years of age who was diagnosed with a pediatric brain tumor of any
             histologic subtype, who has now developed recurrent or refractory disease.

          -  Eligible to receive vaccine injections by TDS-IM electroporation device.

          -  Availability of tissue for sequencing to determine presence of targetable neoantigen.
             This may be fresh tissue collected as part of routine care, another research project
             or archived tissue from a previous craniotomy with biopsy, subtotal resection, total
             gross resection, or re-resection.

          -  Karnofsky/Lansky performance status ≥ 60%

        Normal bone marrow and organ function as defined below:

          -  Absolute neutrophil count ≥ 1,500/mcL

          -  Platelets ≥ 100,000/mcL

          -  Total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN)

          -  AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN

          -  Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m^2 for patients with
             creatinine levels above institutional normal

               -  Systemic corticosteroid therapy is permitted provided dosing is minimal based on
                  age 0.1mg/kg/day with a max of 4mg daily (dexamethasone or equivalent) on the day
                  of vaccine administration.

               -  Bevacizumab will be allowed if given for symptomatic control of vasogenic edema
                  and to avoid high dose of corticosteroids at the discretion of the treating
                  physician.

               -  Women of childbearing 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.

               -  Ability to understand and willingness to sign an IRB approved written informed
                  consent document (or that of legally authorized representative, if applicable).

        Exclusion Criteria:

          -  As this is a safety and feasibility study, prior immunotherapy will be permitted.
             However, any prior immunotherapy must be discontinued at least 2 weeks before vaccine
             administration. Non-immunologic therapy may be continued.

          -  No candidate neoantigen identified during screening.

          -  A history of other malignancy ≤ 3 years previous with the exception of non-melanoma
             skin cancer, any in situ cancer that has been successfully resected and cured, treated
             superficial bladder cancer, or any early-stage solid tumor that was successfully
             resected without need for adjuvant radiation or chemotherapy.

          -  Currently receiving any other investigational agents.

          -  Known allergy, or history of serious adverse reaction to, vaccines such as
             anaphylaxis, hives, or respiratory difficulty.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  History of pre-existing immunodeficiency disorder, autoimmune condition requiring
             immunosuppressive therapy, or chronic infection (i.e. hepatitis B, hepatitis C, HIV).
             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 which might make it difficult for the patient to
             complete the full course of treatments or to generate an immune response to vaccines.

          -  Presence of clinically significant increased intracranial pressure (e.g. impending
             herniation) or hemorrhage, uncontrolled seizures, or requirement for immediate
             palliative treatment.

          -  Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
             pregnancy test within 7 days of first dose of vaccine.

          -  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.

          -  Acute or chronic, clinically significant hematologic, pulmonary, cardiovascular, or
             hepatic or renal functional abnormality as determined by the investigator based on
             medical history, physical examination, EKG, and/or laboratory screening test.

          -  Any chronic or active neurologic disorder, including seizures and epilepsy, excluding
             a single febrile seizure as a child.

          -  Syncopal episode within 12 months of screening.

          -  Current use of any electronic stimulation device, such as cardiac demand pacemakers,
             automatic implantable cardiac defibrillator, nerve stimulators, or deep brain
             stimulators.
      
Maximum Eligible Age:39 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of adjuvant personalized neoantigen DNA vaccine as measured by the number of grade 3 and 4 adverse events
Time Frame:Through 30 days after completion of treatment (estimated to be 13 months)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Median Progression Free Survival (PFS)
Time Frame:2 years
Safety Issue:
Description:PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progressive Disease (PD): At least a 25% increase in the sum of products of perpendicular diameters of at least 1 target lesion, taking as reference the smallest sum of products of perpendicular diameters on study (this includes the baseline sum if that is the smallest on study). The absolute increase in any dimension must be at least 5mm when calculating the products of perpendicular diameters. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy* not caused by comorbid events.
Measure:Median Overall Survival
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Washington University School of Medicine

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