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

Malignant Glioma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00634231
• Other study ID #: PeBrTK01
• Status: Completed
• Phase: Phase 1
• Start date: October 2010
• Est. completion date: June 2021

Study information

• Verified date: August 2023
• Source: Candel Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00729105

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: June 2021
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 21 Years

Eligibility

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)

Related Conditions & MeSH terms

• Ependymoma
• Glioma
• Malignant Glioma
• Recurrent Ependymoma

Intervention

Biological:
• AdV-tk

Drug:
• valacyclovir

Radiation:
• Radiation

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Ann & Robert H. Lurie Children's Hospital of Chicago (Formerly Children's Memorial Hospital)	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Candel Therapeutics, Inc.	Boston Children's Hospital

Country where clinical trial is conducted

United States, 

References & 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 A — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment emergent adverse events		2 months
Secondary	Overall survival		5 years
Secondary	Progression-free survival		5 years
Secondary	Objective tumor response		5 years