Neoplasms

All Conditions

Rare Diseases

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Vaccines

Temozolomide

Poly ICLC

Antineoplastic Agents, Alkylating

Alkylating Agents

Interferons

Immunologic Factors

* For all patients, concurrent chemoradiation with temozolomide will be given per standard of care and is outside the scope of this study as per standard of care.
* The long peptide + poly-ICLC will be given on Cycle 1 Day 1 of maintenance temozolomide.
* If the vaccine is not ready by this time, the first vaccination will begin on Day 1 of the next cycle of maintenance temozolomide.
* The peptide + poly-ICLC vaccine will be given again on Days 8, 15, and 22 of the first cycle, as a priming strategy.
* On all subsequent cycles, the peptide vaccine + poly-ICLC will be given on Day 22 (+/-3 days).

Personalized peptide vaccine

Poly-ICLC

Gavin Dunn, M.D., Ph.D.

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) will provide a reasonably reliable estimate of the safety and immunogenicity of the vaccine.

Neoepitope-based Personalized Vaccine Approach in Patients With Newly Diagnosed Glioblastoma

A Pilot Study to Assess the Safety, Feasibility, and Preliminary Efficacy of a Neoepitope-based Personalized Vaccine Approach in Patients With Newly Diagnosed Glioblastoma

* PFS: duration of time from start of treatment to time of progression or death, whichever occurs first.
* Progression will be evaluated using the updated response assessment criteria for high-grade gliomas: Response Assessment in Neuro-Oncology (RANO) working group guideline

OS: duration of time from start of treatment to time of death from any cause

Washington University School of Medicine

Symptoms and General Pathology

Nervous System Diseases

Recurrence

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Brain Tumor, Childhood

Gastrointestinal Agents

Poly I-C

Carboxymethylcellulose Sodium

Laxatives

Cathartics

Antiviral Agents

* 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.

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

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

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

Peripheral blood draw

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

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.

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

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

-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.

-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.

-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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Neoepitope-based Personalized Vaccine Approach in Patients With Newly Diagnosed Glioblastoma	NCT02510950	Glioblastoma Mu... Astrocytoma, Gr...	Personalized pe... Poly-ICLC Temozolomide	18 Years -	Washington University School of Medicine
Neoepitope-based Personalized Vaccine Approach in Patients With Newly Diagnosed Glioblastoma	NCT02510950	Glioblastoma Mu... Astrocytoma, Gr...	Personalized pe... Poly-ICLC Temozolomide	18 Years -	Washington University School of Medicine
Neoepitope-based Personalized Vaccine Approach in Pediatric Patients With Recurrent Brain Tumors	NCT03068832	Pediatric Brain...	Personalized pe... Poly ICLC Peripheral bloo...	- 21 Years	Washington University School of Medicine

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