Phase 2a Study of AdV-tk With Standard Radiation Therapy for Malignant Glioma (BrTK02) (BrTK02)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Advantagene, Inc.
ClinicalTrials.gov Identifier:
NCT00589875
First received: December 27, 2007
Last updated: March 2, 2016
Last verified: March 2016
  Purpose
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).

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

Resource links provided by NLM:


Further study details as provided by Advantagene, Inc.:

Primary Outcome Measures:
  • 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: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 2016
Primary Completion Date: December 2015 (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:
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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00589875

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
Sponsors and Collaborators
Advantagene, Inc.
Investigators
Principal Investigator: E. Antonio Chiocca, MD, PhD Ohio State University
  More Information

Publications:
Responsible Party: Advantagene, Inc.
ClinicalTrials.gov Identifier: NCT00589875     History of Changes
Other Study ID Numbers: BrTK02 
Study First Received: December 27, 2007
Last Updated: March 2, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Advantagene, Inc.:
Immunotherapy
Cytotoxicity
Tumor vaccine

Additional relevant MeSH terms:
Glioblastoma
Glioma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Valacyclovir
Acyclovir
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 22, 2016