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

Sponsor

Candel Therapeutics, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00634231

Collaborator

Boston Children's Hospital (Other)

Enrollment

Locations

Arm

128

Actual Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Malignant Glioma Recurrent Ependymoma	Biological: AdV-tk Drug: valacyclovir Radiation: Radiation	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

8 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 1, 2010

Actual Primary Completion Date :

Dec 1, 2015

Actual Study Completion Date :

Jun 1, 2021

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: AdV-tk

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

Biological: AdV-tk

Drug: valacyclovir

Other Names:

Prodrug

Radiation: Radiation

Other Names:

Radiation therapy

Outcome Measures

Primary Outcome Measures

Safety based on standard laboratory and clinical adverse event monitoring [2 months]

Secondary Outcome Measures

Overall survival [5 years]
Progression-free survival [5 years]
Objective tumor response [5 years]
Immunologic function [3 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 21 Years

Sexes Eligible for Study:

All

Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ann & Robert H. Lurie Children's Hospital of Chicago (Formerly Children's Memorial Hospital)	Chicago	Illinois	United States	60611
2	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115