Phase 1b Study of AdV-tk + Valacyclovir Combined With Radiation Therapy for Malignant Gliomas - Full Text View

Sponsor:	Advantagene, Inc.
Information provided by:	Advantagene, Inc.
ClinicalTrials.gov Identifier:	NCT00751270

Purpose

This phase I study evaluated a Gene Mediated Cytotoxic Immunotherapy approach for malignant gliomas, including glioblastoma multiforme and anaplastic astrocytoma. The purpose of this study was to assess the safety and feasibility of delivering an experimental approach called GliAtak which uses AdV-tk, an adenoviral vector containing the Herpes Simplex thymidine kinase gene, plus an oral anti-herpetic prodrug, valacyclovir, in combination with standard of care radiation.

Condition	Intervention	Phase
Malignant Glioma Glioblastoma Multiforme Anaplastic Astrocytoma	Biological: AdV-tk Drug: Valacyclovir	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 1b Study of AdV-tk + Valacyclovir Gene Therapy in Combination With Standard Radiation Therapy for Malignant Gliomas

Resource links provided by NLM:

Genetics Home Reference related topics: Help Me Understand Genetics

MedlinePlus related topics: Cancer

Drug Information available for: Valaciclovir Valacyclovir hydrochloride

U.S. FDA Resources

Further study details as provided by Advantagene, Inc.:

Primary Outcome Measures:

Safety of the intervention will be evaluated based on laboratory and clinical parameters graded using CTCAEver3. [ Time Frame: Through month 3 and long term follow up for late effects. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Tumor Response [ Time Frame: MRI imaging and pathological/histological response if available ] [ Designated as safety issue: No ]
Progression-free Survival [ Time Frame: Clinical monitoring, laboratory and radiological imagining and pathological/histological assessments (if performed) ] [ Designated as safety issue: No ]
Overall Survival [ Time Frame: Clinical monitoring, laboratory and radiological imagining and pathological/histological assessments (if performed) ] [ Designated as safety issue: No ]
Quality of Life (QOL) [ Time Frame: Periodic completion of FACT-Br QOL questionaire ] [ Designated as safety issue: No ]

Enrollment:	15
Study Start Date:	November 2005
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A Arm A for unresectable malignant glioma was closed due to poor accrual.	Biological: AdV-tk Three different dosing levels of AdV-tk (3x10e10, 1x10e11, 3X10e11) were evaluated. A single injection of AdV-tk at the assigned dose level was administered, followed by 14 days of the oral prodrug valacyclovir. Patients then received standard of care radiation therapy and chemotherapy. Drug: Valacyclovir The oral prodrug valacyclovir was given beginning 1-3 days following the AdV-tk. Valacyclovir tablets were taken three times a day for a total of 14 days.
Experimental: B Arm B for resectable malignant glioma completed the Phase I accrual and long term follow up continues. A follow on study at dose level 3 was opened as a Phase 2a study (see BrTK02).	Biological: AdV-tk Three different dosing levels of AdV-tk (3x10e10, 1x10e11, 3X10e11) were evaluated. A single injection of AdV-tk at the assigned dose level was administered, followed by 14 days of the oral prodrug valacyclovir. Patients then received standard of care radiation therapy and chemotherapy. Drug: Valacyclovir The oral prodrug valacyclovir was given beginning 1-3 days following the AdV-tk. Valacyclovir tablets were taken three times a day for a total of 14 days.

Arms

Assigned Interventions

Experimental: A

Arm A for unresectable malignant glioma was closed due to poor accrual.

Biological: AdV-tk

Three different dosing levels of AdV-tk (3x10e10, 1x10e11, 3X10e11) were evaluated. A single injection of AdV-tk at the assigned dose level was administered, followed by 14 days of the oral prodrug valacyclovir. Patients then received standard of care radiation therapy and chemotherapy.

Drug: Valacyclovir

The oral prodrug valacyclovir was given beginning 1-3 days following the AdV-tk. Valacyclovir tablets were taken three times a day for a total of 14 days.

Experimental: B

Arm B for resectable malignant glioma completed the Phase I accrual and long term follow up continues. A follow on study at dose level 3 was opened as a Phase 2a study (see BrTK02).

Biological: AdV-tk

Three different dosing levels of AdV-tk (3x10e10, 1x10e11, 3X10e11) were evaluated. A single injection of AdV-tk at the assigned dose level was administered, followed by 14 days of the oral prodrug valacyclovir. Patients then received standard of care radiation therapy and chemotherapy.

Drug: Valacyclovir

The oral prodrug valacyclovir was given beginning 1-3 days following the AdV-tk. Valacyclovir tablets were taken three times a day for a total of 14 days.

Detailed Description:

This study was designed to include patients with newly diagnosed unresectable (Arm A) and resectable (Arm B) malignant glioma. Three dose levels of AdV-tk were evaluated with a fixed dose level of valacyclovir prodrug. AdV-tk was delivered to tumor cells by stereotactic injection into the tumor at the time of biopsy (Arm A) or injection into the tumor bed following resection (Arm B). Oral valacyclovir began 1-3 days after the AdV-tk injection and continued for 14 days. Standard radiation therapy began 3-7 days following the AdV-tk injection to maximize synergy with radiation. Standard temozolomide could be administered after completion of valacyclovir.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Presumed malignant glioma based on clinical and radiologic evaluation (pathologic confirmation of malignant glioma must be made at the time of stereotactic biopsy or resection 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).
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.
Patients must be planning to undergo standard radiation therapy.
Patients must be 18 years of age or older.
Performance status must be KPS > or equal to 70.
Patients must have SGOT (AST) < 3x upper limit of normal.
Patients must have serum creatinine < 2mg/dl and calculated creatinine clearance >10ml/min.
Patients must have 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.
Patients must give study specific informed consent prior to enrollment.
Patients must be able to tolerate MRI scan procedure

Exclusion Criteria:

Prior or ongoing liver disease including known cirrhosis, hepatitis B or C infection but not to exclude patients with a distant history of resolved hepatitis A infection.
Patients on immunosuppressive drugs (with exception of corticosteroid)
Known HIV+ patients.
Patients with 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).
Prior radiation therapy to the brain or prior treatment for brain tumor (except prior biopsy or subtotal resection).
Other serious co-morbid illness or compromised organ function.
Patients may not receive temozolomide until valacyclovir completed and 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 study entry until tumor progression).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00751270

Locations

United States, Ohio
The Ohio State University Medical Center, Dept Neurosurgery
Columbus, Ohio, United States, 43210
United States, Texas
The Methodist Hosptial
Houston, Texas, United States, 77030

Sponsors and Collaborators

Advantagene, Inc.

Investigators

Principal Investigator:

E. Antonio Chiocca, MD, PhD

The Ohio State University Medical Center

More Information

No publications provided

Responsible Party:	Laura Aguilar, MD, PhD, Advantagene, Inc.
ClinicalTrials.gov Identifier:	NCT00751270 History of Changes
Other Study ID Numbers:	BrTK01, 5R44CA107745
Study First Received:	September 9, 2008
Last Updated:	December 23, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Advantagene, Inc.:

Immunotherapy
Gene therapy
Tumor Vaccine
Cytotoxicity
Radiation

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
Acyclovir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012