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

NCT00634231 | Completed Phase 1 DMC

• 1 other identifier: PeBrTK01
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

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.

Conditions

Malignant Glioma; Recurrent Ependymoma

Keywords

Malignant glioma; Glioblastoma multiforme; Anaplastic astrocytoma; Recurrent ependymoma; Gene therapy; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment emergent adverse events

  2 months

Secondary Outcomes (3)

• Overall survival

  5 years

• Progression-free survival

  5 years

• Objective tumor response

  5 years

Study Arms (1)

AdV-tk

EXPERIMENTAL

AdV-tk + valacyclovir in combination with standard of care radiation

Biological: AdV-tk; Drug: valacyclovir; Radiation: Radiation

Interventions

AdV-tk BIOLOGICAL

AdV-tk

valacyclovir DRUG

Also known as: Prodrug

AdV-tk

Radiation RADIATION

Also known as: Radiation therapy

AdV-tk

Eligibility Criteria

• Age: 3 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Candel Therapeutics, Inc.: lead
• Boston Children's Hospital: collaborator

Study Sites (2)

Ann & Robert H. Lurie Children's Hospital of Chicago (Formerly Children's Memorial Hospital)

Chicago, Illinois, 60611, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Kieran MW, Goumnerova L, Manley P, Chi SN, Marcus KJ, Manzanera AG, Polanco MLS, Guzik BW, Aguilar-Cordova E, Diaz-Montero CM, DiPatri AJ, Tomita T, Lulla R, Greenspan L, Aguilar LK, Goldman S. Phase I study of gene-mediated cytotoxic immunotherapy with AdV-tk as adjuvant to surgery and radiation for pediatric malignant glioma and recurrent ependymoma. Neuro Oncol. 2019 Mar 18;21(4):537-546. doi: 10.1093/neuonc/noy202.

  PMID: 30883662 RESULT

MeSH Terms

Conditions

Glioma; Ependymoma; Glioblastoma; Astrocytoma

Interventions

Valacyclovir; Prodrugs; Radiation; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pharmaceutical Preparations; Physical Phenomena; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2008
• First Posted: March 12, 2008
• Study Start: October 1, 2010
• Primary Completion: December 1, 2015
• Study Completion: June 1, 2021
• Last Updated: August 25, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)