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

Diffuse Intrinsic Pontine Glioma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05717712
• Other study ID #: Ad-TD-nsIL12 for primary DIPG
• Status: Recruiting
• Phase: Phase 1
• Start date: January 4, 2023
• Est. completion date: January 4, 2028

Study information

• Verified date: February 2024
• Source: Capital Medical University
• Contact: Xiao Qian, Dr.
• Phone: 18020295435
• Email: ryan521q[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: January 4, 2028
• Est. primary completion date: January 4, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Biological:
• Ad-TD-nsIL12
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.

Locations

Country	Name	City	State
China	Sanbo Brain Hospital, Capital Medical University	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Capital Medical University

Country where clinical trial is conducted

China, 

References & Publications (3)

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):6 — View Citation

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. 2 — View Citation

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( — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Tumor response	To determine tumor response by RAPNO criteria.	3 months after virus injection
Secondary	Over-all survival (12 months)	To determine overall survival at 12 months (OS12).	12 months after virus injection
Secondary	QoL	To measure quality of life baseline assessment and any changes over time by PedsQLTM criteria.	2 years after virus injection
Secondary	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