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

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

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.

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.

Intervention(s) in this Clinical Trial

• Drug: Adv-tk
  • Patients will receive injection of AdV-tk into remaining tumor or tumor bed after resection of malignant glioma. Two dose levels of AdV-tk will be evaluated: Level 1 1x1011 vp per injection Level 2 3x1011 vp per injection Dose escalation will be performed according to the dose escalation and stopping rules in section 7.4 of the protocol with 3-6 patients per dose level.
• Drug: Valacyclovir
  • The prodrug, at a fixed dose, will be started 1-3 days after AdV-tk injection and continue for 14 days.
• Radiation: Radiotherapy
  • Radiation will be determined and administered as per standard of care for the patient's disease. It will start 3-7 days after AdV-tk injection.

Primary Measures

• Safety based on standard laboratory and clinical adverse event monitoring
  • Time Frame: 14 days of valcyclovir
    Safety Issue?: Yes
• Immunologic function
  • Time Frame: 6 weeks
    Safety Issue?: Yes

Secondary Measures

• Overall survival
  • Time Frame: 5 years
    Safety Issue?: Yes
• Progression-free survival
  • Time Frame: 5 years
    Safety Issue?: Yes
• Objective tumor response
  • Time Frame: 5 years
    Safety Issue?: Yes

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).

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 3 Years

Maximum Age for this Clinical Trial: 22 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Dana-Farber Cancer Institute Other

Overall Clinical Trial Officials and Contacts

Mark W Kieran, MD, PhD Study Chair Dana-Farber Cancer Institute  

Overall Contact: Jessica L Lawlor, BA 617-632-5376 Jessical_lawlor@dfci.harvard.edu

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00634231

Study ID Number: 07-098

ClinicalTrials.gov Identifier: NCT00634231

Health Authority: United States: Food and Drug Administration