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

Phase 1

Recruiting

• Conditions: Adverse Drug Event; Diffuse Intrinsic Pontine Glioma; Oncolytic Virus
• Interventions: Biological: Ad-TD-nsIL12

• Registration Number: NCT05717712
• Lead Sponsor: Capital Medical University

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-12-18
• Study Start: 2023-01-04
• Study First Submitted QC: 2023-01-29
• Study First Posted: 2023-02-08
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-25
• Last Update Posted: 2024-02-28
• Primary Completion: 2025-01-04
• Study Completion: 2028-01-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

1. Informed consent of the parents or patient.
2. Patient must be, in the investigator opinion, able to comply with all the protocol procedures.
3. Age 1-18 years.
4. 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).
5. Patient newly diagnosed of DIPG in MRI.
6. Pre-enrollment patients LPS (patients aged ≥1 and <16 years) and KPS (patients aged ≥16 years) ≥ 50.
7. Lesion considered by the investigator to be accessible for stereotactic biopsy. The location of the lesion allows injection without virus entering the ventricular system.
8. No previous treatment for DIPG.

Exclusion Criteria

1. 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℃).
2. Other investigational medications within 30 days prior to viral treatment.
3. Participants with immunodeficiency, autoimmune disease, or active hepatitis.
4. 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.
5. Tumor with multiple location.
6. Pregnant or breast-feeding females.
7. Severe bone marrow hypoplasia.
8. Transaminases (aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)) or total bilirubin > 3 times the upper limit of normal.
9. Neutrophils < 1x10^9/L.
10. Platelets ≤ 100x10^9/L.
11. Hemoglobin < 9 g/dl.
12. Patients with Li-Fraumini syndrome or a known germline defect in the retinoblastoma gene or its associated pathways.
13. Administer any type of vaccine within 30 days prior to Ad-TD-nsIL12 administration.
14. Blood transfusions or drugs (such as G-CSF) within 28 days before baseline to treat pancytopenia or other blood disorders.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental Group	Ad-TD-nsIL12	Multiple intratumoral injections of Ad-TD-nsIL12.

Primary Outcome Measures

Name	Time	Method
Safety of Ad-TD-nsIL12 intratumoral injection in primary pediatric DIPG patients.	3 months after virus injection	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.

Secondary Outcome Measures

Name	Time	Method
Tumor response	3 months after virus injection	To determine tumor response by RAPNO criteria.
Over-all survival (12 months)	12 months after virus injection	To determine overall survival at 12 months (OS12).
QoL	2 years after virus injection	To measure quality of life baseline assessment and any changes over time by PedsQLTM criteria.
Sample Collection	3 months after virus injection	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.

Trial Locations

Locations (1)

Sanbo Brain Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China