Phase 1b Study of AdV-tk + Valacyclovir Combined With Radiation Therapy for Malignant Gliomas (BrTK01)

August 23, 2023 updated by: Candel Therapeutics, Inc.

A Phase 1b Study of AdV-tk + Valacyclovir Gene Therapy in Combination With Standard Radiation Therapy for Malignant Gliomas

This phase I study evaluated a Gene Mediated Cytotoxic Immunotherapy approach for malignant gliomas, including glioblastoma multiforme and anaplastic astrocytoma. The purpose of this study was to assess the safety and feasibility of delivering an experimental approach called GliAtak which uses AdV-tk, an adenoviral vector containing the Herpes Simplex thymidine kinase gene, plus an oral anti-herpetic prodrug, valacyclovir, in combination with standard of care radiation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study was designed to include patients with newly diagnosed unresectable (Arm A) and resectable (Arm B) malignant glioma. Three dose levels of AdV-tk were evaluated with a fixed dose level of valacyclovir prodrug. AdV-tk was delivered to tumor cells by stereotactic injection into the tumor at the time of biopsy (Arm A) or injection into the tumor bed following resection (Arm B). Oral valacyclovir began 1-3 days after the AdV-tk injection and continued for 14 days. Standard radiation therapy began 3-7 days following the AdV-tk injection to maximize synergy with radiation. Standard temozolomide could be administered after completion of valacyclovir.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State University Medical Center, Dept Neurosurgery
    • Texas
      • Houston, Texas, United States, 77030
        • The Methodist Hosptial

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Presumed malignant glioma based on clinical and radiologic evaluation (pathologic confirmation of malignant glioma must be made at the time of stereotactic biopsy or resection prior to AdV-tk injection; if this is not possible, the injection will not be performed and the subject will no longer be eligible for the study).
  • Tumor must be accessible for injection and must not be located in the brainstem, midbrain, contained within the ventricular system, or located in an infratentorial location.
  • Patients must be planning to undergo standard radiation therapy.
  • Patients must be 18 years of age or older.
  • Performance status must be KPS > or equal to 70.
  • Patients must have SGOT (AST) < 3x upper limit of normal.
  • Patients must have serum creatinine < 2mg/dl and calculated creatinine clearance >10ml/min.
  • Patients must have platelets > 100,000/mm3 and WBC > 3000/mm3.
  • Patients of reproductive age must agree to use a medically accepted form of birth control while on the study.
  • Patients must give study specific informed consent prior to enrollment.
  • Patients must be able to tolerate MRI scan procedure

Exclusion Criteria:

  • Prior or ongoing liver disease including known cirrhosis, hepatitis B or C infection but not to exclude patients with a distant history of resolved hepatitis A infection.
  • Patients on immunosuppressive drugs (with exception of corticosteroid)
  • Known HIV+ patients.
  • Patients with acute infections (viral, bacterial or fungal infections requiring therapy).
  • Pregnant or breast feeding patients. Female patients of childbearing age must have negative serum or urine pregnancy test within 1 week of beginning therapy.
  • Evidence of metastatic disease or other malignancy (except squamous or basal cell skin cancers).
  • Prior radiation therapy to the brain or prior treatment for brain tumor (except prior biopsy or subtotal resection).
  • Other serious co-morbid illness or compromised organ function.
  • Patients may not receive temozolomide until valacyclovir completed and may not receive other investigational anti-tumor agents within 30 days prior to study entry or during active participation in the study (defined as from study entry until tumor progression).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A
Arm A for unresectable malignant glioma was closed due to poor accrual.
Biological: AdV-tk
Three different dosing levels of AdV-tk (3x10e10, 1x10e11, 3X10e11) were evaluated. A single injection of AdV-tk at the assigned dose level was administered, followed by 14 days of the oral prodrug valacyclovir. Patients then received standard of care radiation therapy and chemotherapy.
Drug: Valacyclovir
The oral prodrug valacyclovir was given beginning 1-3 days following the AdV-tk. Valacyclovir tablets were taken three times a day for a total of 14 days.
Experimental: B
Arm B for resectable malignant glioma completed the Phase I accrual and long term follow up continues. A follow on study at dose level 3 was opened as a Phase 2a study (see BrTK02).
Biological: AdV-tk
Three different dosing levels of AdV-tk (3x10e10, 1x10e11, 3X10e11) were evaluated. A single injection of AdV-tk at the assigned dose level was administered, followed by 14 days of the oral prodrug valacyclovir. Patients then received standard of care radiation therapy and chemotherapy.
Drug: Valacyclovir
The oral prodrug valacyclovir was given beginning 1-3 days following the AdV-tk. Valacyclovir tablets were taken three times a day for a total of 14 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of treatment emergent adverse events
Time Frame: Through month 3 and long term follow up for late effects.
Through month 3 and long term follow up for late effects.

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall Survival
Time Frame: 5 years
5 years
Progression-free Survival
Time Frame: Clinical monitoring, laboratory and radiological imagining and pathological/histological assessments (if performed)
Clinical monitoring, laboratory and radiological imagining and pathological/histological assessments (if performed)
Functional Assessment of Cancer Therapy - Brain (FACT-Br)
Time Frame: 24 months
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Candel Therapeutics, Inc.

Investigators

  • Principal Investigator: E. Antonio Chiocca, MD, PhD, Ohio State University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2005

Primary Completion (Actual)

January 1, 2010

Study Completion (Actual)

January 1, 2011

Study Registration Dates

First Submitted

September 9, 2008

First Submitted That Met QC Criteria

September 10, 2008

First Posted (Estimated)

September 11, 2008

Study Record Updates

Last Update Posted (Actual)

August 25, 2023

Last Update Submitted That Met QC Criteria

August 23, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BrTK01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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