ADV-TK Improves Outcome of Recurrent High-Grade Glioma

Study Overview
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Brief Summary
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Malignant gliomas are the most common primary brain tumor in adults, but the prognosis for patients with these tumors remains poor despite advances in diagnosis and standard therapies such as surgery, radiation therapy, and chemotherapy. The advantages of ADV-TK gene therapy highlight its efficacy and safety for glioma patients. This clinical trial was conducted to assess the anti-tumor efficacy and safety of intraarterial cerebral infusion of replication-deficient adenovirus mutant ADV-TK, in combination with systemic intravenous GCV administration in patients with recurrent high-grade glioma.

Official Title
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Adenovirus-Mediated Delivery of Herpes Simplex Virus Thymidine Kinase Administration Improves Outcome of Recurrent High-Grade Glioma

Conditions
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Malignant Glioma of Brain, Glioblastoma

Intervention / Treatment
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* Biological: ADV-TK/GCV
* Procedure: Surgery
* Drug: systemic chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed WHO grades 3 to 4 malignant glioma Diagnosed recurrence or progression by clinical or radiological evidence Fit for intraarterial infusion and intravenous chemotherapy Adequate hepatic, renal, and hematologic function. Legal age ≥18 years Life expectancy ≥12 weeks Eastern Cooperative Oncology Group performance (ECOG) ≥2 Chemotherapy completion ≥4 weeks prior and recovery from drug induced toxicities. Exclusion Criteria: Active pregnancy Prior gene therapy Second primary tumor Gravidity, lactation, hypersensitivity to antiviral drugs, immunologic deficit, active uncontrolled infections Requiring treatment with warfarin or any other anticoagulants

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADV-TK/GCV<br>ADV-TK was administered via intraarterial cerebral infusion. Systemic GCV therapy was delivered at a dose of 5mg/kg intravenous, every 12 h at 36 hours after ADV-TK therapy. | Biological: ADV-TK/GCV<br>* gene therapy<br>|
| Active Comparator: Control group<br>Patients received surgery or systemic chemotherapy or palliative care. | Procedure: Surgery<br> <br> Drug: systemic chemotherapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary end point was 6-month progression-free survival rate (PFS-6) |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival (PFS) |  | 3 years | 
| overall survival (OS) |  | 3 years | 
| safety |  | 1. at the time during treatments; 2. at 6-month; 3. at the end of 1-year following-up; 4. at the end of 2-year following up; 5. at the time the patient censored. | 
| clinical benefit | the rate of complete response, plus partial response, plus stable disease | at the end of 2nd ADK-TK/GCV therapy |