Official Title: “A Phase 2a Study of AdV-tk + Valacyclovir Gene Therapy in Combination With Standard Radiation Therapy for Malignant Glioma”

The purpose of this study is to evaluate the safety and potential efficacy of Gene Mediated Cytotoxic Immunotherapy for malignant gliomas. The approach uses an adenoviral vector (disabled virus) engineered to express the Herpes thymidine kinase gene (AdV-tk), followed by an antiherpetic prodrug, valacyclovir. The AdV-tk vector is injected into the tumor bed after standard tumor surgery and valacyclovir pills are taken for 14 days. Standard radiation and chemotherapy are administered which have been shown to work cooperatively with AdV-tk + prodrug to kill tumor cells. The hypothesis is that this combination therapy can be safely delivered and will lead to improvement in the clinical outcome for patients with newly diagnosed malignant gliomas, including glioblastoma multiforme (WHO grade IV) and anaplastic astrocytomas (WHO grade III).

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: September 2009

Intervention(s) in this Clinical Trial

• Biological: AdV-tk
  • Single dose of 3x10e11 vector particles of AdV-tk delivered into remaining tumor or tumor bed after resection on day 0.
• Drug: Valacyclovir
  • Single course of valacyclovir at dose of 2 grams orally three times per day for 14 days starting on day 1-3

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Single arm, Arm B
  • This study is an extension of evaluation of the surgical resection arm, Arm B, from a phase Ib study in which dose escalation on arm B was completed. Arm A, biopsy only, is still enrolling on the phase Ib study.

Primary Measures

• Expand the safety evaluation at the maximum dose of AdV-tk evaluated in a completed phase Ib study
  • Time Frame: 2 months
    Safety Issue?: Yes

Secondary Measures

• Overall survival
  • Time Frame: 24 motnhs
    Safety Issue?: No
• Progression free survival
  • Time Frame: 24 months
    Safety Issue?: No
• Quality of life
  • Time Frame: 24 months
    Safety Issue?: No

Inclusion Criteria:

• Must have presumed malignant glioma based on clinical and radiologic evaluation and pathologic confirmation of malignant glioma must be made at the time of surgery if not previously determined
• 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.
• Must be planning to undergo standard radiation therapy.
• Performance status KPS 70 or more.
• SGOT (AST) < 3x upper limit of normal.
• Serum creatinine < 2mg/dl and calculated creatinine clearance >10ml/min.
• 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.
• Must give study specific informed consent prior to enrollment.
• 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.
• 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.
• May not receive temozolomide until valacyclovir completed
• 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).

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Advantagene, Inc.

Overall Clinical Trial Officials and Contacts

E. Antonio Chiocca, MD, PhD Principal Investigator The Ohio State University Medical Center  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00589875

Study ID Number: BrTK02

ClinicalTrials.gov Identifier: NCT00589875

Health Authority: United States: Food and Drug Administration