Adverse Drug Event, Diffuse Intrinsic Pontine Glioma, Oncolytic Virus
Conditions
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).
Interventions
BIOLOGICALAd-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.
Sponsors
Capital Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 18 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Over-all survival (12 months) | 12 months after virus injection | To determine overall survival at 12 months (OS12). |
| Tumor response | 3 months after virus injection | To determine tumor response by RAPNO criteria. |
| 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. |
Countries
China
Contacts
Primary ContactXiao Qian, Dr.
Outcome results
None listed