Safety and Immunogenicity of Personalized Genomic Vaccine and Tumor Treating Fields (TTFields) to Treat Glioblastoma

Study Overview
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Brief Summary
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The purpose of this study is to use precision medicine in the form of a vaccine, a mutation-derived tumor antigen vaccine (MTA-based vaccine) in combination with standard care treatment of glioblastoma (GBM) and Tumor Treating Fields (TTFields). The study is designed to determine whether this treatment combination is well tolerated and safe.

Detailed Description
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This is a single-arm, single institution phase 1a / 1b study to test the safety, tolerability, and immunogenicity of MTA-based personalized vaccine in patients with newly diagnosed GBM along with the use of continual TTFields. MTA-based personalized vaccine is prepared in the laboratory with several peptides based on each patient's own tumor sequence. The vaccine is given after the radiation and chemotherapy portion of the treatment, in the maintenance phase of temozolomide in conjunction with the TTFields.

Official Title
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Phase I Study of Tumor Treatment Fields and a Personalized Mutation-derived Tumor Vaccine in Patients With Newly Diagnosed Glioblastoma (GCO 17-0566)

Conditions
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Glioblastoma

Intervention / Treatment
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* Drug: Poly-ICLC
* Device: Tumor Treating Fields
* Biological: Peptides


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 Confirmation of GBM (WHO grade IV). Maximal debulking surgery and undergo radiotherapy concomitant with Temozolomide (45-70Gy) Stable disease after treatment of radiation with chemotherapy Life expectancy > 16 weeks. Performance status of 0-2 (Eastern Cooperative Oncology Group). First vaccine treatment start date at least 4 weeks out but not more than 8 weeks from the last dose of concomitant Temozolomide or radiotherapy. Must have tumor tissue sufficient sequencing. Have adequate bone marrow function Require Dexamethasone ≤ 4mg daily on a stable dose Acceptable hematologic, hepatic, and renal function and these tests must be performed within 14 days prior to study The participant must be deemed competent to give informed consent. The participant must agree to use two effective forms of contraception beginning at least four (4) weeks prior to study entry. Exclusion Criteria: Progression of disease at time of screening. Implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias. Infra-tentorial tumor or multifocal disease. History of hypersensitivity reaction to Temozolomide. Receiving any other investigational agents. Prior history of unrelated neoplastic disease, and having received systemic therapy for the secondary malignancy within the twelve (12) month period preceding the screening evaluation. (HIV/AIDS), Chronic hepatitis B or hepatitis C. History of, or is reasonably suspected to meet criteria for the diagnosis of a known congenital or acquired disorder causing systemic immunosuppression. History of, or is reasonably suspected to meet criteria for the diagnosis of a systemic auto-immune/inflammatory disease or other autoimmune disorder with the exception of: Vitiligo Positive pregnancy test [45 CFR 46.203(b)]. (CFR = Code of Federal Regulations)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mutation-derived tumor vaccine<br>MTA-based Personalized Vaccine (peptides + Poly-ICLC with Tumor Treating Fields | Drug: Poly-ICLC<br>* Poly-ICLC 100mcg per peptide per dose<br>* Other names: Hiltonol®;Device: Tumor Treating Fields<br>* an FDA approved treatment for patients with recurrent GBM and newly diagnosed GBM<br>* Other names: Optune®;Biological: Peptides<br>* synthetic long peptides (SLP) as vaccine substrate<br>* Other names: Personalized peptides;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicities (DLT) | Feasibility administration of one vaccine; toxicity will be measured by severity of Adverse events with toxicity grading defined by Cancer Therapy Evaluation Program's (CTEP) v4.0 of National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) scale | 42 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity grading using CTCAE scale | Safety will be measured by number of Adverse events with toxicity grading defined by Cancer Therapy Evaluation Program's (CTEP) v4.0 of National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) scale | 1 year | 
| The percent Progression Free Survival (PFS) |  | 6 months | 
| Overall Survival (OS) Rate |  | 1 year | 
| Overall Response Rate | Overall response as measured by RANO (Response assessment in neuro-oncology) Response Criteria: Complete response, Partial response, Stable Disease, and Progressive Disease | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GBM, Brain cancer, Glioblastoma, Personalized vaccine, Poly-ICLC (polyinosinic-polycytidylic acid), Immunotherapy, Cancer, NovoTTF-200A, Optune, immunogenicity