Clinical trial NCT05717712: Oncolytic Virus Ad-TD-nsIL12 for Primary Pediatric Diffuse Intrinsic Pontine Glioma
Official title: Oncolytic Virus Ad-TD-nsIL12 for Primary Pediatric Diffuse Intrinsic Pontine Glioma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Oncolytic Virus
Diffuse Intrinsic Pontine Glioma
Adverse Drug Event
Lead sponsor: Capital Medical University
Sponsor class: OTHER
First posted: 2023-02-08
Enrollment: 18
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Safety of Ad-TD-nsIL12 intratumoral injection in primary pediatric DIPG patients.
timeFrame: 3 months after virus injection
Secondary outcomes:
measure: Tumor response
timeFrame: 3 months after virus injection
measure: Over-all survival (12 months)
timeFrame: 12 months after virus injection
measure: QoL
timeFrame: 2 years after virus injection
measure: Sample Collection
timeFrame: 3 months after virus injection
Other outcomes:
Locations:
city: Beijing
country: China
facility: Sanbo Brain Hospital, Capital Medical University
state: Beijing
Study officials:
affiliation: Capital Medical University
name: Hongwei Zhang, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
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(11):2438. doi: 10.3390/cells9112438.
citation: 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.
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. 2017 Nov 9;8(1):1395. doi: 10.1038/s41467-017-01385-8.