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

Condition(s) targeted: Malignant Glioma; Glioblastoma Multiforme; Anaplastic Astrocytoma

Intervention: AdV-tk (Biological); Valacyclovir (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Advantagene, Inc.

Official(s) and/or principal investigator(s):
E. Antonio Chiocca, MD, PhD, Principal Investigator, Affiliation: The Ohio State University Medical Center

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).

Official title: A Phase 2a Study of AdV-tk + Valacyclovir Gene Therapy in Combination With Standard Radiation Therapy for Malignant Glioma

Study design: Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Safety/Efficacy Study

Primary outcome: Expand the safety evaluation at the maximum dose of AdV-tk evaluated in a completed phase Ib study

Secondary outcome:

Overall survival

Progression free survival

Quality of life

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Must have presumed malignant glioma based on clinical and radiologic evaluation and

pathologic confirmation of malignant glioma must be made at the time of surgery if not previously determined

- 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.

- 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.

- 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.

- May not receive temozolomide 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 study entry until tumor progression).

City of Hope Medical Center, Duarte, California 91010, United States; Recruiting
Greta Manila, NP, Phone: 626-471-9393
Roger Harthrong, NP, Phone: 626-471-9393
Jana Portnow, MD, Principal Investigator

The Ohio State University Medical Center, Dept. Neurological Surgery, Columbus, Ohio 43210, United States; Recruiting
Susan D Bell, RN,MS, Phone: 614-293-3143, Email: Susan.Bell@osumc.edu
E. Antonio Chiocca, MD, PhD, Phone: 614-293-9312
E. Antonio Chiocca, MD, PhD, Principal Investigator

The Methodist Hospital Neurological Institute, Houston, Texas 77030, United States; Recruiting
Pamela Z. New, MD, Phone: 713-441-3800, Email: pnew@tmhs.org
Pamela Z New, MD, Principal Investigator
David Baskin, MD, Sub-Investigator
Todd Trask, MD, Sub-Investigator

Starting date: March 2007
Last updated: February 4, 2009