Phase 2a Study of AdV-tk With Standard Radiation Therapy for Malignant Glioma (BrTK02)
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Malignant Glioma Glioblastoma Multiforme Anaplastic Astrocytoma |
Biological: AdV-tk Drug: Valacyclovir |
Phase 2 |
| Study Type: | Interventional |
| 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 ]
| Enrollment: | 52 |
| 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) |
| Arms | Assigned Interventions |
|---|---|
|
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.
|
Biological: AdV-tk
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
|
Detailed Description:
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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).
Contacts and Locations| 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 | The Ohio State University Medical Center |
More Information
No publications provided
| Responsible Party: | Advantagene, Inc. |
| ClinicalTrials.gov Identifier: | NCT00589875 History of Changes |
| Other Study ID Numbers: | BrTK02, 5R44CA107745 |
| Study First Received: | December 27, 2007 |
| Last Updated: | February 24, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Advantagene, Inc.:
|
Immunotherapy Cytotoxicity Tumor vaccine |
Additional relevant MeSH terms:
|
Astrocytoma Glioblastoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms |
Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Valacyclovir Antiviral Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions |
ClinicalTrials.gov processed this record on October 17, 2012
