This trial is active, not recruiting.

Conditions malignant glioma, glioblastoma multiforme, anaplastic astrocytoma
Treatments adv-tk, valacyclovir
Phase phase 2
Sponsor Advantagene, Inc.
Start date March 2007
End date December 2015
Trial size 52 participants
Trial identifier NCT00589875, BrTK02


The purpose of this study was to evaluate the safety and potential efficacy of Gene Mediated Cytotoxic Immunotherapy for malignant gliomas. The approach used an adenoviral vector (disabled virus) engineered to express the Herpes thymidine kinase gene (aglatimagene besadenovec, AdV-tk), followed by an antiherpetic prodrug, valacyclovir. The AdV-tk vector was injected into the resection bed after standard tumor surgery and valacyclovir pills were taken for 14 days. Standard radiation and chemotherapy were 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).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
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.
Single dose of 3x10e11 vector particles of AdV-tk delivered to the tumor bed after resection on day 0.
valacyclovir Valtrex
Single course of valacyclovir at dose of 2 grams orally three times per day for 14 days starting on day 1-3

Primary Outcomes

Expand the safety evaluation at the maximum dose of AdV-tk evaluated in a completed phase Ib study
time frame: 2 months
Overall survival
time frame: 5 years

Secondary Outcomes

Progression free survival
time frame: 24 months
Quality of life
time frame: 24 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Must have presumed resectable or partially resectable malignant glioma based on clinical and radiologic evaluation (pathologic confirmation of malignant glioma must be made at the time of surgery if not previously determined). Patients who have previously received AdV-tk + prodrug on this study may receive an additional AdV-tk + prodrug course at recurrence if eligibility criteria are still met. - 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. For re-administration, patients must be re-consented. - Must be able to tolerate MRI scan procedure Exclusion Criteria: - Active liver disease including cirrhosis or hepatitis - 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). - Other serious co-morbid illness or compromised organ function. - May not receive chemotherapy 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 AdV-tk injection until tumor progression).

Additional Information

Official title A Phase 2a Study of AdV-tk + Valacyclovir Gene Therapy in Combination With Standard Radiation Therapy for Malignant Glioma
Principal investigator E. Antonio Chiocca, MD, PhD
Description Patients had resectable or partially resectable malignant glioma and received injection of AdV-tk into remaining tumor or tumor bed after resection. Pathologic confirmation of malignant glioma must be made prior to AdV-tk injection; if this was not possible, the injection was not performed and the subject was no longer eligible for the study. The oral prodrug, valacyclovir, started 1-3 days after AdV-tk injection and continued for 14 days. Standard radiotherapy began on average 7 days after AdV-tk injection for the up-front course. Patients received temozolomide as per standard of care after completion of prodrug.
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by Advantagene, Inc..