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

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.

Study Overview

• Status: Completed
• Conditions: Malignant Glioma; Recurrent Ependymoma
• Intervention / Treatment: Radiation: Radiation; Drug: valacyclovir; Biological: AdV-tk

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 Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago (Formerly Children's Memorial Hospital)
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AdV-tk; AdV-tk + valacyclovir in combination with standard of care radiation	Radiation: Radiation; Other Names: Radiation therapy; Drug: valacyclovir; Other Names: Prodrug; Biological: AdV-tk

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of treatment emergent adverse events	2 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	5 years
Progression-free survival	5 years
Objective tumor response	5 years

Collaborators and Investigators

• Sponsor: Candel Therapeutics, Inc.
• Collaborators: Boston Children's Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2010
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): June 1, 2021

Study Registration Dates

• First Submitted: March 5, 2008
• First Submitted That Met QC Criteria: March 5, 2008
• First Posted (Estimated): March 12, 2008

Study Record Updates

• Last Update Posted (Actual): August 25, 2023
• Last Update Submitted That Met QC Criteria: August 23, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Immunotherapy; Anaplastic astrocytoma; Gene therapy; Glioblastoma multiforme; Recurrent ependymoma; Malignant glioma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Ependymoma; Anti-Infective Agents; Antiviral Agents; Valacyclovir
• Other Study ID Numbers: PeBrTK01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO