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

Candel Therapeutics

Status and phase

Completed

Phase 1

Conditions

Recurrent Ependymoma

Malignant Glioma

Treatments

Biological: AdV-tk

Radiation: Radiation

Drug: valacyclovir

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00634231

PeBrTK01

Details and patient eligibility

About

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.

Full 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.

Enrollment

8 patients

Sex

All

Ages

3 to 21 years old

Volunteers

No Healthy Volunteers

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)