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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: Poly-ICLC; Device: Tumor Treating Fields; Biological: Peptides

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10461
      • Albert Einstein College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Albert Einstein College of Medicine
• Collaborators: NovoCure Ltd.
• Investigators: Principal Investigator: Adilia Hormigo, MD, PhD, Albert Einstein College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Actual): July 31, 2020
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: July 18, 2017
• First Submitted That Met QC Criteria: July 18, 2017
• First Posted (Actual): July 19, 2017

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Cancer; GBM; Immunotherapy; immunogenicity; Glioblastoma; Brain cancer; Personalized vaccine; Optune; NovoTTF-200A; Poly-ICLC (polyinosinic-polycytidylic acid)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Physiological Effects of Drugs; Immunologic Factors; Interferon Inducers; Poly ICLC
• Other Study ID Numbers: 2022-13817; 16-089 (Other Identifier: PRMC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes