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

Condition(s) targeted: Childhood Cancer

Intervention: Adv-tk (Drug); Valacyclovir (Drug); Radiotherapy (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

Overall contact:
Jay B Pietrantonio, BA, Phone: 617-632-6740, Email: Jayb_Pietrantonio@dfci.harvard.edu

The primary objectives of this study are to evaluate whether the administration of AdV-tk to malignant brain tumors followed by anti-herpetic prodrug in combination with radiation therapy will be safe, can be effectively delivered without disturbing standard therapy and will have anti-tumor activity in pediatric patients with 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, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study

Primary outcome:

Safety based on standard laboratory and clinical adverse event monitoring

Immunologic function

Secondary outcome:

Overall survival

Progression-free survival

Objective tumor response

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

Minimum age: 3 Years. Maximum age: 22 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients must have newly diagnosed supratentorial malignant glioma

- Patients must be 3 years of age or older.

- Tumor must be accessible for injection and must not be located in the brainstem, deep

midbrain, contained within the ventricular system, or located in an infratentorial location.

- Patients must be planning to undergo standard radiation therapy.

- 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 of > 1000/ µl (unsupported), hemoglobin 8. 0 gm/dL (may be supported), and platelet count > 100,000/ µl (unsupported)

- 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 x 1. 5 times institutional normal; SGPT (ALT) <3x

institutional normal for age

- Chemistry Function: Normal electrolyte values including sodium, potassium,

magnesium, calcium

- Patients with seizure disorder may be enrolled if well controlled.

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.

- Prior radiation therapy to the brain or prior treatment for brain tumor except for

surgery.

- 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).

Jay B Pietrantonio, BA, Phone: 617-632-6740, Email: Jayb_Pietrantonio@dfci.harvard.edu

Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States; Recruiting
Mark W Kieran, MD, PhD, Phone: 617-632-4907, Email: mark_kieran@dfci.harvard.edu
Jay Pietrantonio, BA, Phone: 617-632-6740, Email: JayB_Pietrantonio@DFCI.HARVARD.EDU
Mark W Kieran, MD, PhD, Principal Investigator

Starting date: April 2008
Last updated: May 7, 2009