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

NCT ID: NCT03068832

Last Updated: 2021-05-25

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-30
• Study Completion Date: 2026-02-28

Brief Summary

The early clinical development paradigm for chemotherapeutic agents has significantly influenced the development of therapeutic cancer vaccines. However, there are major differences between these two classes of therapeutics that have important implications for early clinical development. Specifically, the phase 1 concept of dose escalation to find a maximum-tolerated dose does not apply to most therapeutic cancer vaccines. Most therapeutic cancer vaccines are associated with minimal toxicity at a range that is feasible to manufacture or administer, and there is little reason to believe that the maximum-tolerated dose is the most effective dose.

In a recent article from the biostatistics literature, Simon et al. write that "the initial clinical trial of many new vaccines will not be a toxicity or dose-ranging trial but rather will involve administration of a fixed dose of vaccine … in most cases the dose selected will be based on preclinical findings or practical considerations. Using several dose levels in the initial study to find the minimal active dose or to characterize the dose-activity relationship is generally not realistic".

Consistent with these recommendations, the general philosophy of the phase 1 clinical trial is to facilitate a prompt preliminary evaluation of the safety and immunogenicity of the personalized synthetic long peptide vaccine strategy. The proposed clinical trial will test a fixed dose of vaccine. There is considerable experience with the synthetic long peptide vaccine platform. The synthetic long peptide vaccine platform has an excellent safety profile, and the optimal dose appears to be based on practical considerations (solubility of the peptide). The dose to be tested in the proposed clinical trial is consistent with other similar cancer vaccine trials that have been recently completed or are currently ongoing. The sample size (n=10-20) will provide a reasonably reliable estimate of the safety and immunogenicity of the vaccine.

Conditions

Pediatric Brain Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Personalized peptide vaccine and poly-ICLC

• The synthetic long peptide(s) and poly-ICLC will be given on Cycle 1 Day 1 when available.
• Additional peptide vaccine doses will be administered again on Days 4, 8, 15, and 22 of the first cycle as a priming strategy. On all subsequent cycles, the peptide vaccine will be given on Day 1.
• Peptide vaccine administration will continue until supply is exhausted or development of intolerance or disease progression in the case of fatal high grade neoplasms. Otherwise, vaccination will continue until supply is exhausted or 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 if remaining vaccine is available.

Group Type: EXPERIMENTAL

Personalized peptide vaccine

Intervention Type: BIOLOGICAL

-It may take 3-4 months for sequencing, neoantigen prediction, and peptide manufacturing

Poly ICLC

Intervention Type: DRUG

-Poly-ICLC is supplied by Oncovir in single-dose vials containing 1 mL of 2 mg/mL opalescent white suspension.

Peripheral blood draw

Intervention Type: PROCEDURE

• After trial enrollment and up to 7 days after the 1st vaccine dose
• 2 weeks after last dose
• Time of progression or discontinuation

Interventions

Personalized peptide vaccine

-It may take 3-4 months for sequencing, neoantigen prediction, and peptide manufacturing

Intervention Type: BIOLOGICAL

Poly ICLC

-Poly-ICLC is supplied by Oncovir in single-dose vials containing 1 mL of 2 mg/mL opalescent white suspension.

Intervention Type: DRUG

Peripheral blood draw

• After trial enrollment and up to 7 days after the 1st vaccine dose
• 2 weeks after last dose
• Time of progression or discontinuation

Intervention Type: PROCEDURE

Other Intervention Names

Poly-ICLC; Hiltonol

Eligibility Criteria

Inclusion Criteria

• Any patient, regardless of current age, who was diagnosed between the ages of 0-21 years with a pediatric brain tumor of any histologic subtype, who has now developed recurrent or refractory disease.
• 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 m2 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 peptide 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.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to poly-ICLC or other agents used in the study.
• 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.

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joshua Rubin, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Related Links

http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

201807123

Identifier Type: -

Identifier Source: org_study_id