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

NCT ID: NCT05717712

Last Updated: 2024-02-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-04
• Study Completion Date: 2028-01-04

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental Group

Multiple intratumoral injections of Ad-TD-nsIL12.

Group Type: EXPERIMENTAL

Ad-TD-nsIL12

Intervention Type: 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.

Interventions

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Capital Medical University

OTHER

Sponsor Role: lead

Responsible Party

Hongwei Zhang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hongwei Zhang, Prof.

Role: PRINCIPAL_INVESTIGATOR

Capital Medical University

Locations

Sanbo Brain Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xiao Qian, Dr.

Role: CONTACT

ryan521q@sina.com

18020295435

Facility Contacts

Weihai Ning, Dr.

Role: primary

sanboocean@163.com

+86 15961868172

References

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.

Reference Type: RESULT

PMID: 33182528 (View on PubMed)

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.

Reference Type: RESULT

PMID: 19223865 (View on PubMed)

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.

Reference Type: RESULT

PMID: 29123084 (View on PubMed)

Other Identifiers

Ad-TD-nsIL12 for primary DIPG

Identifier Type: -

Identifier Source: org_study_id