Back to resultsA Phase I Study of AdV-tk + Prodrug Therapy in Combination With Radiation Therapy for Pediatric Brain Tumors
Primary Purpose
Malignant Glioma, Recurrent Ependymoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AdV-tk
valacyclovir
Radiation
Sponsored by
About this trial
This is an interventional treatment trial for Malignant Glioma focused on measuring Malignant glioma, Glioblastoma multiforme, Anaplastic astrocytoma, Recurrent ependymoma, Gene therapy, Immunotherapy
Eligibility Criteria
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)
Sites / Locations
- Ann & Robert H. Lurie Children's Hospital of Chicago (Formerly Children's Memorial Hospital)
- Dana-Farber Cancer Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
AdV-tk
Arm Description
AdV-tk + valacyclovir in combination with standard of care radiation
Outcomes
Primary Outcome Measures
Incidence of treatment emergent adverse events
Secondary Outcome Measures
Overall survival
Progression-free survival
Objective tumor response
Full Information
NCT ID
NCT00634231
First Posted
March 5, 2008
Last Updated
August 23, 2023
Sponsor
Candel Therapeutics, Inc.
Collaborators
Boston Children's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT00634231
Brief Title
A Phase I Study of AdV-tk + Prodrug Therapy in Combination With Radiation Therapy for Pediatric Brain Tumors
Official Title
A Phase I Study of AdV-tk + Prodrug Therapy in Combination With Radiation Therapy for Pediatric Brain Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
October 2010 (Actual)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
June 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Candel Therapeutics, Inc.
Collaborators
Boston Children's Hospital
4. Oversight
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Glioma, Recurrent Ependymoma
Keywords
Malignant glioma, Glioblastoma multiforme, Anaplastic astrocytoma, Recurrent ependymoma, Gene therapy, Immunotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AdV-tk
Arm Type
Experimental
Arm Description
AdV-tk + valacyclovir in combination with standard of care radiation
Intervention Type
Biological
Intervention Name(s)
AdV-tk
Intervention Type
Drug
Intervention Name(s)
valacyclovir
Other Intervention Name(s)
Prodrug
Intervention Type
Radiation
Intervention Name(s)
Radiation
Other Intervention Name(s)
Radiation therapy
Primary Outcome Measure Information:
Title
Incidence of treatment emergent adverse events
Time Frame
2 months
Secondary Outcome Measure Information:
Title
Overall survival
Time Frame
5 years
Title
Progression-free survival
Time Frame
5 years
Title
Objective tumor response
Time Frame
5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Facility Information:
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago (Formerly Children's Memorial Hospital)
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
30883662
Citation
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.
Results Reference
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A Phase I Study of AdV-tk + Prodrug Therapy in Combination With Radiation Therapy for Pediatric Brain Tumors
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