Oncolytic Virus Ad-TD-nsIL12 for Primary Pediatric Diffuse Intrinsic Pontine Glioma

Study Overview
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Brief Summary
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This is a drug safety assessment clinical trial with a 3+3 dose escalation design, to observe the safety, tolerability and toxicity of a novel oncolytic virus Ad-TD-nsIL12 intratumoral injection in primary DIPG patients (NCI-CTCAE V5.0).

Official Title
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Oncolytic Virus Ad-TD-nsIL12 for Primary Pediatric Diffuse Intrinsic Pontine Glioma

Conditions
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Oncolytic Virus, Diffuse Intrinsic Pontine Glioma, Adverse Drug Event

Intervention / Treatment
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* Biological: Ad-TD-nsIL12


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent of the parents or patient. Patient must be, in the investigator opinion, able to comply with all the protocol procedures. Age 1-18 years. A negative pregnancy test in fertile women (women are considered of childbearing potential (WOCBP) after menarche, unless permanently infertile, including hysterectomy, bilateral salpingectomy, and bilateral oophorectomy). Patient newly diagnosed of DIPG in MRI. Pre-enrollment patients LPS (patients aged ≥1 and <16 years) and KPS (patients aged ≥16 years) ≥ 50. Lesion considered by the investigator to be accessible for stereotactic biopsy. The location of the lesion allows injection without virus entering the ventricular system. No previous treatment for DIPG. Exclusion Criteria: Serious infections or intercurrent conditions, including but not limited to severe renal failure, liver failure, heart failure, or bone marrow failure, which are not permitted for inclusion according to the investigator's criteria. Patients must be afebrile at baseline (<38℃). Other investigational medications within 30 days prior to viral treatment. Participants with immunodeficiency, autoimmune disease, or active hepatitis. Any medical or psychological condition that might interfere with the patient's ability to participate if older than 16 years or parents ability when younger than 16, or give informed consent or would compromise the patient's ability to tolerate therapy or any disease that will obscure toxicity or dangerously alter drug metabolism. Tumor with multiple location. Pregnant or breast-feeding females. Severe bone marrow hypoplasia. Transaminases (aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)) or total bilirubin > 3 times the upper limit of normal. Neutrophils < 1x10^9/L. Platelets ≤ 100x10^9/L. Hemoglobin < 9 g/dl. Patients with Li-Fraumini syndrome or a known germline defect in the retinoblastoma gene or its associated pathways. Administer any type of vaccine within 30 days prior to Ad-TD-nsIL12 administration. Blood transfusions or drugs (such as G-CSF) within 28 days before baseline to treat pancytopenia or other blood disorders.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group<br>Single intratumoral injection of Ad-TD-nsIL12. Total dose will be 3x10^9vp, 1x10^10vp or 3x10^10 vp suspended in 1 ml according to cohort design. | Biological: Ad-TD-nsIL12<br>* This is a novel adenovirus 5-based Ad-TD, which had three gene deletions (E1ACR2, E1B19K and E3gp19K) but retains the E3B gene. This new mutant oncolytic adenovirus exhibited strong anti-tumor efficacy in vivo. On the basis of Ad-TD, Ad-TD-nsIL12 is armed with human non-secretory interleukin-12 (nsIL12, deletion of the signal peptide).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of Ad-TD-nsIL12 intratumoral injection in primary pediatric DIPG patients. | The trial will look for possible hematologic and neurologic toxicity of Ad-TD-nsIL12 by NCI-CTCAE v5.0 to determine maximum tolerated dose of this oncolytic adenovirus. | 3 months after virus injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response | To determine tumor response by RAPNO criteria. | 3 months after virus injection | 
| Over-all survival (12 months) | To determine overall survival at 12 months (OS12). | 12 months after virus injection | 
| QoL | To measure quality of life baseline assessment and any changes over time by PedsQLTM criteria. | 2 years after virus injection | 
| Sample Collection | Pre- and post- treatment tumor tissue will be collected and tested to determine the immune response of patients. Collected blood will be used to test possible hematotoxicity of Ad-TD-nsIL12. | 3 months after virus injection |