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

NCT00751270 | Completed Phase 1 DMC

• 1 other identifier: BrTK01
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Malignant Glioma; Glioblastoma Multiforme; Anaplastic Astrocytoma

Keywords

Immunotherapy; Gene therapy; Tumor Vaccine; Cytotoxicity; Radiation

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment emergent adverse events

  Through month 3 and long term follow up for late effects.

Secondary Outcomes (3)

• Progression-free Survival

  Clinical monitoring, laboratory and radiological imagining and pathological/histological assessments (if performed)

• Overall Survival

  5 years

• Functional Assessment of Cancer Therapy - Brain (FACT-Br)

  24 months

Study Arms (2)

A

EXPERIMENTAL

Arm A for unresectable malignant glioma was closed due to poor accrual.

Biological: AdV-tk; Drug: Valacyclovir

B

EXPERIMENTAL

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; Drug: Valacyclovir

Interventions

AdV-tk BIOLOGICAL

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.

A; B

Valacyclovir DRUG

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.

A; B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Candel Therapeutics, Inc.: lead

Study Sites (2)

The Ohio State University Medical Center, Dept Neurosurgery

Columbus, Ohio, 43210, United States

Location

The Methodist Hosptial

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Chiocca EA, Aguilar LK, Bell SD, Kaur B, Hardcastle J, Cavaliere R, McGregor J, Lo S, Ray-Chaudhuri A, Chakravarti A, Grecula J, Newton H, Harris KS, Grossman RG, Trask TW, Baskin DS, Monterroso C, Manzanera AG, Aguilar-Cordova E, New PZ. Phase IB study of gene-mediated cytotoxic immunotherapy adjuvant to up-front surgery and intensive timing radiation for malignant glioma. J Clin Oncol. 2011 Sep 20;29(27):3611-9. doi: 10.1200/JCO.2011.35.5222. Epub 2011 Aug 15.

  PMID: 21844505 RESULT

Related Links

• Phase IB study of gene-mediated cytotoxic immunotherapy adjuvant to up-front surgery and intensive timing radiation for malignant glioma

MeSH Terms

Conditions

Glioma; Glioblastoma; Astrocytoma

Interventions

Valacyclovir

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• E. Antonio Chiocca, MD, PhD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2008
• First Posted: September 11, 2008
• Study Start: November 1, 2005
• Primary Completion: January 1, 2010
• Study Completion: January 1, 2011
• Last Updated: August 25, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)