Neoepitope-based Personalized Vaccine Approach in Pediatric Patients With Recurrent Brain Tumors
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|ClinicalTrials.gov Identifier: NCT03068832|
Recruitment Status : Not yet recruiting
First Posted : March 3, 2017
Last Update Posted : September 16, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Pediatric Brain Tumor||Biological: Personalized peptide vaccine Drug: Poly ICLC Procedure: Peripheral blood draw||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study to Assess the Safety, Feasibility, and Preliminary Efficacy of a Neoepitope-based Personalized Vaccine Approach in Pediatric Patients With Recurrent Brain Tumors|
|Estimated Study Start Date :||November 30, 2020|
|Estimated Primary Completion Date :||May 31, 2022|
|Estimated Study Completion Date :||April 30, 2025|
Experimental: Personalized peptide vaccine and poly-ICLC
Biological: Personalized peptide vaccine
-It may take 3-4 months for sequencing, neoantigen prediction, and peptide manufacturing
Drug: Poly ICLC
-Poly-ICLC is supplied by Oncovir in single-dose vials containing 1 mL of 2 mg/mL opalescent white suspension.
Procedure: Peripheral blood draw
- Safety and tolerability of adjuvant personalized neoantigen peptide vaccine administration with poly-ICLC as measured by grade 3 and 4 adverse events [ Time Frame: Up to 30 days following last day of study treatment (up to 4 months) ]-As defined by CTCAE v. 4.03
- Feasibility of adjuvant personalized neoantigen peptide vaccine administration with poly-ICLC as measured by the number of participants who have a neoantigen specific long peptide vaccine identified and generated [ Time Frame: 12-14 weeks ]-The vaccine study drug is a frozen solution for injection. It is a personalized vaccine composed of up to 20 synthesized peptides that are approximately 20 to 35 amino acids in length. The peptides are designed to generate an immune response to neoantigens found in each patient's tumor.
- Characterize tumor-infiltrating lymphocytes (TIL) [ Time Frame: Up to 2 weeks after the last dose (up to 4 months) ]-Paired t-test or paired-sample Wilcoxon Signed Rank test will be used to compare the gene expression of TIL in blood as measured before and after treatment.
- Frequency of expressed neoantigens using patient-specific HLA class I prediction algorithms [ Time Frame: Completion of treatment (up to 3 months) ]-Up to 20 of the highest priority sequencing-identified mutant tumor-specific antigens that are confirmed to bind and stabilize HLA class I molecules will be targeted
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03068832
|Contact: Joshua Rubin, M.D., Ph.D.||firstname.lastname@example.org|
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|Contact: Joshua Rubin, M.D., Ph.D. 314-454-6018 email@example.com|
|Principal Investigator: Joshua Rubin, M.D., Ph.D.|
|Sub-Investigator: Tanner M Johanns, M.D., Ph.D.|
|Sub-Investigator: William E Gillanders, M.D.|
|Sub-Investigator: Robert Schreiber, Ph.D.|
|Sub-Investigator: Maxim Artyomov, Ph.D.|
|Sub-Investigator: David Spencer, M.D., Ph.D.|
|Sub-Investigator: David Limbrick, M.D., Ph.D.|
|Sub-Investigator: Allison King, M.D., MPH|
|Sub-Investigator: Milan Chheda, M.D.|
|Sub-Investigator: George Ansstas, M.D.|
|Sub-Investigator: Jian Campian, M.D.|
|Principal Investigator:||Joshua Rubin, M.D., Ph.D.||Washington University School of Medicine|