Phase I Trial of DNX-2401 for Diffuse Intrinsic Pontine Glioma newly diagnosed in pediatric patients.

Phase 1

• Conditions: Diffuse Intrinsic Pontine Glioma newly diagnosed in pediatric patients.; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-001577-33-ES
• Lead Sponsor: Clínica Universidad de Navarra

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-08-18
• Study Completion: 2022-01-24
• Last Update Posted: 26 September 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

1. Informed consent OF PATIENT OR PARENTS
2. Patient must be, in the investigator opinion, able to comply with all the protocol procedures.
3. Age 1 - 18 years
4. Negative pregnant blood test in case of fertile women (A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
5. Patient newly diagnosed of DIPG in MRI
6. Lansky Performance Status = 70 before inclusion
7. Lesion considered by the investigator to be accessible for stereotactic biopsy. Lesion location will allow injection without entrance of virus in the ventricular system.
8. No previous treatment for DIPG
Are the trial subjects under 18? yes
Number of subjects for this age range: 12
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Severe infections or intercurrent medical conditions including, but not limited to, severe renal, hepatic, heart or bone marrow failure, that, on investigator´s criteria, do not allow the inclusion. Patients must be afebrile at baseline [i.e., < 38 degrees (Cº)].
2. Investigational medication in the previous 30 days.
3. Subjects with immunodeficiency, autoimmune conditions or active hepatitis.
4. Any medical or psychological condition that might interfere with the subject'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 locations or doubt in MRI of a DIPG.
6. Pregnant or breast-feeding females will be excluded, due to the risk for the fetal development of a recombinant virus containing genes related to cellular growth and differentiation.
7. Severe bone marrow hypoplasia.
8. AST and/or ALT > 3 times over upper normal laboratory level
9. Neutrophils < 1 x 109/L
10. Thrombocytes = 100 x 109/L
11. Hemoglobin < 9g/dl
13. Patients with Li-Fraumini Syndrome or with a known germ line deficit in the retinoblastoma gene or its related pathways.
14. Vaccinations of any kind within 30 days prior to DNX-2401 administration.
15. Transfusions or medications (G-CSF) to treat pancytopenia or other hematological conditions within 28 days of baseline.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the safety, tolerability and toxicity of DNX-2401 injected in the cerebellar peduncle in pediatric subjects with DIPG. The trial will look for hematologic and neurologic toxicity (NCI-CTCAE v 4.03).;Secondary Objective: •To determine Overall Survival at 12 months (OS12), complete/partial response in MRI, immune response induced by DNX-2401.<br>•To measure quality of life (QoL) baseline assessment and any changes over time<br>•To collect tumor and blood samples for futures molecular and immune studies.;Primary end point(s): To determine the safety, tolerability and toxicity of DNX-2401 injected in the cerebellar peduncle in pediatric subjects with DIPG. The trial will look for hematologic and neurologic toxicity.;Timepoint(s) of evaluation of this end point: For each individual patient the timepoint of evaluation will be two months after DNX.2401 injection, Fort he whole trial, could be 26-30 months (if the 12 patients are recruited along 24 months)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - To determine Overall Survival at 12 months (OS12), complete/partial response in MRI and immune response induced by DNX-2401.<br>- To measure quality of life (QoL) baseline assessment and any changes over time.<br>- To collect tumor and blood samples for futures molecular and immune studies.;Timepoint(s) of evaluation of this end point: 12 months after virus injection.