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

NCT05717712 | Recruiting Phase 1

• 1 other identifier: Ad-TD-nsIL12 for primary DIPG
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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).

Conditions

Oncolytic Virus; Diffuse Intrinsic Pontine Glioma; Adverse Drug Event

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Tumor response

  3 months after virus injection

• Over-all survival (12 months)

  12 months after virus injection

• QoL

  2 years after virus injection

• Sample Collection

  3 months after virus injection

Study Arms (1)

Experimental Group

EXPERIMENTAL

Multiple intratumoral injections of Ad-TD-nsIL12.

Biological: Ad-TD-nsIL12

Interventions

Ad-TD-nsIL12 BIOLOGICAL

After stereotactic biopsy, the Ommaya reservoir will be inserted through the biopsy channel and two injections of Ad-TD-nsIL12 will be delivered after surgery by Ommaya reservoir (with an interval of 3 days). The interval between following injections in the subsequent treatment period will be 3 weeks ±4 days. The assigned dose for each patient will be 3x10\^9vp, 1x10\^10vp or 3x10\^10 vp suspended in 1 ml NS according to cohort design.

Experimental Group

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Capital Medical University: lead

Study Sites (1)

Sanbo Brain Hospital, Capital Medical University

Beijing, Beijing Municipality, 100010, China

RECRUITING

Related Publications (3)

• Zhang Z, Zhang C, Miao J, Wang Z, Wang Z, Cheng Z, Wang P, Dunmall LSC, Lemoine NR, Wang Y. A Tumor-Targeted Replicating Oncolytic Adenovirus Ad-TD-nsIL12 as a Promising Therapeutic Agent for Human Esophageal Squamous Cell Carcinoma. Cells. 2020 Nov 10;9(11):2438. doi: 10.3390/cells9112438.

  PMID: 33182528 RESULT

• Bortolanza S, Bunuales M, Otano I, Gonzalez-Aseguinolaza G, Ortiz-de-Solorzano C, Perez D, Prieto J, Hernandez-Alcoceba R. Treatment of pancreatic cancer with an oncolytic adenovirus expressing interleukin-12 in Syrian hamsters. Mol Ther. 2009 Apr;17(4):614-22. doi: 10.1038/mt.2009.9. Epub 2009 Feb 17.

  PMID: 19223865 RESULT

• Wang P, Li X, Wang J, Gao D, Li Y, Li H, Chu Y, Zhang Z, Liu H, Jiang G, Cheng Z, Wang S, Dong J, Feng B, Chard LS, Lemoine NR, Wang Y. Re-designing Interleukin-12 to enhance its safety and potential as an anti-tumor immunotherapeutic agent. Nat Commun. 2017 Nov 9;8(1):1395. doi: 10.1038/s41467-017-01385-8.

  PMID: 29123084 RESULT

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma; Drug-Related Side Effects and Adverse Reactions

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Chemically-Induced Disorders

Study Officials

• Hongwei Zhang, Prof.

  Capital Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiao Qian, Dr.

CONTACT

18020295435; ryan521q@sina.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 18, 2022
• First Posted: February 8, 2023
• Study Start: January 4, 2023
• Primary Completion: January 4, 2025
• Study Completion (Estimated): January 4, 2028
• Last Updated: February 28, 2024

Record last verified: 2024-02

Locations

CN (1)