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

Primary Purpose

Oncolytic Virus, Diffuse Intrinsic Pontine Glioma, Adverse Drug Event

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Ad-TD-nsIL12
Sponsored by
Capital Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Oncolytic Virus

Eligibility Criteria

1 Year - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Informed consent of the parents or patient. After surgical resection, biopsy, chemotherapy, or radiation therapy, tumor progression must be confirmed by MRI scan. Biopsy is performed prior to injection of Ad-TD-nsIL12 to confirm DIPG (frozen section-based). Pre-enrollment patients LPS (patients aged ≥1 and <16 years) and KPS (patients aged ≥16 years) ≥ 50. 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). Lesion considered by the investigator to be accessible for stereotactic biopsy. Exclusion Criteria: 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 (<38℃) at the time of viral therapy. 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 < 9g/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 viral treatment to treat pancytopenia or other hematological disorders.

Sites / Locations

  • Sanbo Brain Hospital, Capital Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental Group

Arm Description

Single intratumoral injection of Ad-TD-nsIL12. Total dose will be 3x10^9vp, 1x10^10vp or 3x10^10 vp suspended in 1 ml according to cohort design.

Outcomes

Primary Outcome Measures

Safety of Ad-TD-nsIL12 intratumoral injection in progressive 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.

Secondary Outcome Measures

Tumor response
To determine tumor response by RAPNO criteria
Over-all survival
To determine overall survival at 12 months (OS12).
QoL
To measure quality of life baseline assessment and any changes over time by PedsQLTM criteria.
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.

Full Information

First Posted
December 18, 2022
Last Updated
January 29, 2023
Sponsor
Capital Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT05717699
Brief Title
Oncolytic Virus Ad-TD-nsIL12 for Progressive Pediatric Diffuse Intrinsic Pontine Glioma
Official Title
Oncolytic Virus Ad-TD-nsIL12 for Progressive Pediatric Diffuse Intrinsic Pontine Glioma
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 4, 2023 (Actual)
Primary Completion Date
January 4, 2025 (Anticipated)
Study Completion Date
January 4, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Capital Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This is a single-arm, single-center, 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 progressive DIPG patients (NCI-CTCAE V5.0).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oncolytic Virus, Diffuse Intrinsic Pontine Glioma, Adverse Drug Event

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental Group
Arm Type
Experimental
Arm Description
Single intratumoral injection of Ad-TD-nsIL12. Total dose will be 3x10^9vp, 1x10^10vp or 3x10^10 vp suspended in 1 ml according to cohort design.
Intervention Type
Biological
Intervention Name(s)
Ad-TD-nsIL12
Intervention Description
This is a novel adenovirus 5-based Ad-TD, which had three gene deletions (E1ACR2, E1B19K and E3gp19K) but retains the E3B gene. This new mutant oncolytic adenovirus exhibited strong anti-tumor efficacy in vivo. On the basis of Ad-TD, Ad-TD-nsIL12 is armed with human non-secretory interleukin-12 (nsIL12, deletion of the signal peptide).
Primary Outcome Measure Information:
Title
Safety of Ad-TD-nsIL12 intratumoral injection in progressive pediatric DIPG patients.
Description
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.
Time Frame
3 months after virus injection
Secondary Outcome Measure Information:
Title
Tumor response
Description
To determine tumor response by RAPNO criteria
Time Frame
3 months after virus injection
Title
Over-all survival
Description
To determine overall survival at 12 months (OS12).
Time Frame
12 months after virus injection
Title
QoL
Description
To measure quality of life baseline assessment and any changes over time by PedsQLTM criteria.
Time Frame
2 years after virus injection
Title
Sample Collection
Description
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.
Time Frame
3 months after virus injection

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Informed consent of the parents or patient. After surgical resection, biopsy, chemotherapy, or radiation therapy, tumor progression must be confirmed by MRI scan. Biopsy is performed prior to injection of Ad-TD-nsIL12 to confirm DIPG (frozen section-based). Pre-enrollment patients LPS (patients aged ≥1 and <16 years) and KPS (patients aged ≥16 years) ≥ 50. 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). Lesion considered by the investigator to be accessible for stereotactic biopsy. Exclusion Criteria: 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 (<38℃) at the time of viral therapy. 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 < 9g/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 viral treatment to treat pancytopenia or other hematological disorders.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xiao Qian, Dr.
Phone
18020295435
Email
ryan521q@sina.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hongwei Zhang, Prof.
Organizational Affiliation
Capital Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sanbo Brain Hospital, Capital Medical University
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100010
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Weihai Ning, Dr.
Phone
+86 15961868172
Email
sanboocean@163.com

12. IPD Sharing Statement

Citations:
PubMed Identifier
33182528
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.
Results Reference
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PubMed Identifier
19223865
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.
Results Reference
background
PubMed Identifier
29123084
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. Erratum In: Nat Commun. 2018 Jan 10;9(1):203.
Results Reference
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Oncolytic Virus Ad-TD-nsIL12 for Progressive Pediatric Diffuse Intrinsic Pontine Glioma

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