Phase 2a Study of AdV-tk With Standard Radiation Therapy for Malignant Glioma (BrTK02)
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). In addition, re-treatment at recurrence is being evaluated in patients who previously received AdV-tk + prodrug on this study.
Accrual of new patients has been completed. The study remains open for evaluation and re-treatment at recurrence.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2a Study of AdV-tk + Valacyclovir Gene Therapy in Combination With Standard Radiation Therapy for Malignant Glioma|
- Expand the safety evaluation at the maximum dose of AdV-tk evaluated in a completed phase Ib study [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
- Overall survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]
- Progression free survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]
- Quality of life [ Time Frame: 24 months ] [ Designated as safety issue: No ]
|Study Start Date:||March 2007|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Experimental: Single arm
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.Drug: Valacyclovir
Single course of valacyclovir at dose of 2 grams orally three times per day for 14 days starting on day 1-3
Other Name: Valtrex
Up-front patients must have resectable or partially resectable malignant glioma and receive 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 is not possible, the injection will not be performed and the subject will no longer be eligible for the study.
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.
The dose level of AdV-tk is 3x10e11 vector particles. The oral prodrug, valacyclovir, is started 1-3 days after AdV-tk injection and continue for 14 days. Standard radiotherapy will begin 3-7 days after AdV-tk injection for the up-front course. For the recurrent course, if radiation is indicated, it will also begin 3-7 days after AdV-tk injection.
Patients may receive temozolomide as per standard of care after completion of prodrug. For recurrent administration, standard of care chemotherapy may be administered after completion of prodrug.
|United States, California|
|City of Hope Medical Center|
|Duarte, California, United States, 91010|
|United States, Illinois|
|The University of Chicago|
|Chicago, Illinois, United States, 60637|
|United States, Ohio|
|The Ohio State University Medical Center, Dept. Neurological Surgery|
|Columbus, Ohio, United States, 43210|
|United States, Texas|
|The Methodist Hospital Neurological Institute|
|Houston, Texas, United States, 77030|
|Principal Investigator:||E. Antonio Chiocca, MD, PhD||Ohio State University|