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

Study Overview
=================
Brief Summary
-----------------
This study will evaluate the administration of AdV-tk followed by valacyclovir in children with malignant glioma, including glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA), as well as recurrent ependymomas in combination with radiation therapy. The primary objective is to determine if this approach is safe and can be effectively delivered without disturbing standard therapy.

Detailed Description
-----------------
This is an Open label, Phase I, dose escalation study. Patients will receive an injection of AdV-tk into the tumor or tumor bed during the surgical procedure followed by 14 days of anti-herpetic prodrug, valacyclovir, starting 1-3 days after vector injection. Standard radiotherapy will begin 3-7 days after AdV-tK injection. Standard chemotherapy may begin after completion of valacyclovir at the discretion of the treating physician and family. Two dose levels of AdV-tk will be evaluated with a fixed dose of valacyclovir.

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

Conditions
-----------------
Malignant Glioma, Recurrent Ependymoma

Intervention / Treatment
-----------------
* Biological: AdV-tk
* Drug: valacyclovir
* Radiation: Radiation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must be 3 years of age or older Patients must be planning to undergo standard of care treatment with surgery and radiation therapy. Patients must have malignant glioma or recurrent ependymoma Tumor must be accessible for injection and must not be located in the brainstem or deep midbrain Performance Score: Karnofsky ≥60% if >10y/o, Lansky ≥60 if ≤10y/o Bone Marrow Function: Patients must have adequate bone marrow function defined as a peripheral absolute neutrophil count ≥ 1000/µl, platelet count ≥ 100,000/µl (transfusion independent) and hemoglobin ≥ 8.0 gm/dL Renal Function: Patients must have serum creatinine ≤ 1.5 times upper limit of institutional normal for age and/or GFR ≥ 70 mL/min/1.73 m2. Hepatic Function: Bilirubin ≤ 1.5 times institutional normal; SGPT (ALT) < 3 times institutional normal Serum electrolyte values (sodium, potassium, magnesium, calcium) must be checked prior to enrollment and clinically significant abnormalities corrected prior to surgery/AdV-tk injection Patients with seizure disorder may be enrolled if well controlled Signed informed consent according to institutional guidelines must be obtained 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 history of HIV or underlying immunodeficiency 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 Other serious co-morbid illness or compromised organ function No 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)

Ages Eligible for Study
-----------------
Minimum Age: 3 Years
Maximum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AdV-tk<br>AdV-tk + valacyclovir in combination with standard of care radiation | Biological: AdV-tk<br> <br> Drug: valacyclovir<br> <br> * Other names: Prodrug;Radiation: Radiation<br> <br> * Other names: Radiation therapy;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events |  | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 5 years | 
| Progression-free survival |  | 5 years | 
| Objective tumor response |  | 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Malignant glioma, Glioblastoma multiforme, Anaplastic astrocytoma, Recurrent ependymoma, Gene therapy, Immunotherapy