Neoepitope-based Personalized Vaccine Approach in Patients With Newly Diagnosed Glioblastoma
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|ClinicalTrials.gov Identifier: NCT02510950|
Recruitment Status : Terminated (Low accrual)
First Posted : July 29, 2015
Last Update Posted : November 17, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma Multiforme Astrocytoma, Grade IV||Biological: Personalized peptide vaccine Drug: Poly-ICLC Drug: Temozolomide||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1 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 Patients With Newly Diagnosed Glioblastoma|
|Actual Study Start Date :||December 3, 2015|
|Actual Primary Completion Date :||February 14, 2017|
|Actual Study Completion Date :||February 14, 2017|
Experimental: Arm 1: Peptide/poly-ICLC
Biological: Personalized peptide vaccine
Other Name: HiltonolDrug: Temozolomide
Other Name: Temodar®
- Safety and tolerability of adjuvant personalized neoantigen peptide vaccine with poly-ICLC as measured by grade 3 and 4 adverse events as defined by CTCAE v. 4.03 [ Time Frame: 30 days after completion of treatment (approximately 7 months) ]
- Feasibility of the peptide vaccine with poly-ICLC as measured by the ability to identify patient tumor-derived candidate neoantigens and generate a tumor-specific vaccine from time of initial diagnosis to time of proposed administration of the vaccine [ Time Frame: Approximately 12-14 weeks ]
- Progression-free survival (PFS) rate [ Time Frame: Up to 24 months after last dose of vaccine ]
- 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
- Overall survival (OS) rate [ Time Frame: Up to 24 months after last dose of vaccine ]OS: duration of time from start of treatment to time of death from any cause
- Number of neoantigens present in patients with newly diagnosed GBM [ Time Frame: After completion of treatment (approximately 6 months) ]
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): NCT02510950
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|Principal Investigator:||Gavin Dunn, M.D., Ph.D.||Washington University School of Medicine|