Gene Therapy, Valacyclovir, and Radiation Therapy in Treating Young Patients With Newly Diagnosed Supratentorial Malignant Glioma

Condition(s) targeted: Brain and Central Nervous System Tumors

Intervention: adenoviral vector encoding HSV thymidine kinase (Biological); valacyclovir (Drug); conventional surgery (Procedure); neoadjuvant therapy (Procedure); radiation therapy (Radiation)

Phase: Phase 1

Status: Recruiting

Sponsored by: Dana-Farber Cancer Institute

Official(s) and/or principal investigator(s):
Mark W. Kieran, MD, PhD, Study Chair, Affiliation: Dana-Farber Cancer Institute

RATIONALE: Gene therapy and valacyclovir may stimulate the immune system in different ways and stop tumor cells from growing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving gene therapy and valacyclovir together with radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of gene therapy given together with valacyclovir and radiation therapy in treating young patients with newly diagnosed supratentorial malignant glioma.

Official title: A Phase I Study of AdV-tk + Prodrug Therapy in Combination With Radiation Therapy for Pediatric Brain Tumors

Study design: Treatment, Open Label

Primary outcome: Maximum tolerated dose of adenoviral vector encoding herpes simplex virus thymidine kinase

Secondary outcome:

Overall survival

Progression-free survival

Objective tumor response

Detailed description: OBJECTIVES:

Primary

- To evaluate the safety of adjuvant adenoviral vector encoding herpes simplex virus

thymidine kinase when administered with valacyclovir and standard radiotherapy in pediatric patients with newly diagnosed, supratentorial malignant glioma.

Secondary

- To assess tumor response, progression-free survival, and overall survival of patients

treated with this regimen.

OUTLINE: This is a dose-escalation study of adenoviral vector encoding herpes simplex virus (HSV) thymidine kinase.

Patients undergo craniotomy with resection of malignant glioma. Patients receive adenoviral vector encoding HSV thymidine kinase (AdV-tk) subcutaneously into up to 10 sites in the wall of the resection cavity into the remaining tumor or tumor bed. Patients receive valacyclovir orally or IV beginning 1-3 days after AdV-tk injection and continuing for 14 days. Patients also undergo standard radiotherapy beginning 3-7 days after AdV-tk injection.

After completion of study therapy, patients are followed once a year for 5 years and then periodically thereafter.

Minimum age: 3 Years. Maximum age: 18 Years. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- Diagnosis of supratentorial malignant glioma meeting the following criteria:

- Newly diagnosed disease

- Tumor must be accessible for injection

- Tumor must not be located in the brainstem or deep midbrain, contained within the

ventricular system, or located in an infratentorial location

- Must be planning to undergo standard radiotherapy

PATIENT CHARACTERISTICS:

- Karnofsky performance status (PS) 60-100% (patients > 10 years of age) or Lansky PS

60-100% (patients ≤ 10 years of age)

- ANC ≥ 1,000/mm³ (transfusion independent)

- Hemoglobin ≥ 8. 0 gm/dL (transfusion allowed)

- Platelet count ≥ 100,000/mm³ (transfusion independent)

- Serum creatinine ≤ 1. 5 times upper limit of normal for age and/or glomerular

filtration rate ≥ 70 mL/min

- Bilirubin ≤ 1. 5 times normal

- ALT < 3 times normal

- Electrolytes (i. e., sodium, potassium, magnesium, and calcium) normal

- Seizure disorder allowed provided it is well controlled

- No prior or ongoing liver disease, including known cirrhosis or hepatitis B or C

infection

- Distant history of resolved hepatitis A infection allowed

- No known history of HIV

- No underlying immunodeficiency

- No acute infections (i. e., viral, bacterial, or fungal infections requiring therapy)

- Not pregnant or nursing

- Negative pregnancy test

- No other serious comorbid illness or compromised organ function

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior radiotherapy to the brain or prior treatment for brain tumor except for

surgery

- More than 30 days since prior and no other concurrent investigational antitumor

agents

- No concurrent immunosuppressive drugs, with the exception of corticosteroids

Children's Hospital Boston, Boston, Massachusetts 02115, United States; Recruiting
Clinical Trials Office - Children's Hospital Boston, Phone: 800-828-6622; 617-632-2506

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston, Massachusetts 02115, United States; Recruiting
Mark W. Kieran, MD, PhD, Phone: 617-632-4907

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: June 2008
Last updated: February 6, 2009