Phase 2a Study of AdV-tk With Standard Radiation Therapy for Malignant Glioma (BrTK02)
This trial is active, not recruiting.
|Conditions||malignant glioma, glioblastoma multiforme, anaplastic astrocytoma|
|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|
|Duarte, CA||City of Hope Medical Center||no longer recruiting|
|Chicago, IL||The University of Chicago||no longer recruiting|
|Columbus, OH||The Ohio State University Medical Center, Dept. Neurological Surgery||no longer recruiting|
|Houston, TX||The Methodist Hospital Neurological Institute||no longer recruiting|
|Endpoint classification||safety/efficacy study|
|Intervention model||single group assignment|
Expand the safety evaluation at the maximum dose of AdV-tk evaluated in a completed phase Ib study
time frame: 2 months
time frame: 5 years
Progression free survival
time frame: 24 months
Quality of life
time frame: 24 months
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).
|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.|
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