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

Phase 1

Completed

• Conditions: Recurrent Ependymoma; Malignant Glioma
• Interventions: Biological: AdV-tk; Drug: valacyclovir; Radiation: Radiation

• Registration Number: NCT00634231
• Lead Sponsor: Candel Therapeutics, Inc.

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.

Study Timeline

• Study First Submitted: 2008-03-05
• Study First Submitted QC: 2008-03-05
• Study First Posted: 2008-03-12
• Study Start: 2010-10
• Primary Completion: 2015-12
• Study Completion: 2021-06
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-23
• Last Update Posted: 2023-08-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AdV-tk	Radiation	AdV-tk + valacyclovir in combination with standard of care radiation
AdV-tk	AdV-tk	AdV-tk + valacyclovir in combination with standard of care radiation
AdV-tk	valacyclovir	AdV-tk + valacyclovir in combination with standard of care radiation

Primary Outcome Measures

Name	Time	Method
Incidence of treatment emergent adverse events	2 months

Secondary Outcome Measures

Name	Time	Method
Progression-free survival	5 years
Overall survival	5 years
Objective tumor response	5 years

Trial Locations

Locations (2)

Ann & Robert H. Lurie Children's Hospital of Chicago (Formerly Children's Memorial Hospital); 🇺🇸 Chicago, Illinois, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States