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

Glioblastoma Multiforme Clinical Trial

— BrTK01  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00751270
• Other study ID #: BrTK01
• Status: Completed
• Phase: Phase 1
• Start date: November 2005
• Est. completion date: January 2011

Study information

• Verified date: August 2023
• Source: Candel Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: January 2011
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Anaplastic Astrocytoma
• Astrocytoma
• Glioblastoma
• Glioblastoma Multiforme
• Glioma
• Malignant Glioma

Intervention

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.

Locations

Country	Name	City	State
United States	The Ohio State University Medical Center, Dept Neurosurgery	Columbus	Ohio
United States	The Methodist Hosptial	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Candel Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

References & 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 o — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment emergent adverse events		Through month 3 and long term follow up for late effects.
Secondary	Progression-free Survival		Clinical monitoring, laboratory and radiological imagining and pathological/histological assessments (if performed)
Secondary	Overall Survival		5 years
Secondary	Functional Assessment of Cancer Therapy - Brain (FACT-Br)		24 months

External Links

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