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Oncolytic Adenovirus, DNX-2401, for Naive Diffuse Intrinsic Pontine Gliomas

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ClinicalTrials.gov Identifier: NCT03178032
Recruitment Status : Unknown
Verified July 2020 by Clinica Universidad de Navarra, Universidad de Navarra.
Recruitment status was:  Active, not recruiting
First Posted : June 6, 2017
Last Update Posted : July 16, 2020
DNAtrix, Inc.
Alcyone Lifesciences, Inc.
Information provided by (Responsible Party):
Clinica Universidad de Navarra, Universidad de Navarra

Brief Summary:
Oncolytic adenovirus for pediatric naive DIPG, to be infused after tumor biopsy through the same trajectory in the cerebellar peduncle.

Condition or disease Intervention/treatment Phase
Brainstem Glioma Neoadjuvant Therapy Biological: DNX-2401 Phase 1

Detailed Description:
Diffuse pontine gliomas (DIPG) are one of the most lethal pediatric tumors. All treatment approaches for these tumors have failed, leaving a terrible prospect with median survival under one year, and survival at 5 years virtually of zero. Moreover, most of the long term survivors suffer from long-term side effects of the aggressive treatment. Thus, new therapeutic strategies are required that allow not only for more effective treatments of these tumors but also that defer the severe side effects derived from the current therapeutic choices. DNX-2401 is an oncolytic virus engineered to replicate specifically in tumor cells with an abnormal retinoblastoma (RB) pathway. Moreover, this virus infects cells through integrins, which are more abundant in glioma cells. Here we propose a phase I, unicentric, non-randomized clinical trial to study the safety and potential efficacy of intratumoral administration of DNX-2401 in DIPG. The virus administration will be done after stereotactic tumor biopsy, using the same trajectory, after verification of catheter position with intraoperative MRI. After 3-4 weeks patients will receive standard radiotherapy and/or chemotherapy. The primary objective is to confirm the safety of the target dose known from adults trials. Secondary endpoints are overall survival at 12 months (OS12), percentage of responses and induced immune response against tumor. The follow up includes close monitoring of neurological status, blood tests and brain MRI. If this trial shows evidence of safety and efficacy will propel a multicenter clinical trial.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Trial of DNX-2401 for Diffuse Intrinsic Pontine Glioma Newly Diagnosed in Pediatric Patients.
Actual Study Start Date : May 26, 2017
Estimated Primary Completion Date : January 31, 2021
Estimated Study Completion Date : January 31, 2021

Arm Intervention/treatment
Experimental: single arm treatment DNX-2401
Single arm receiving virus DNX-2401 infusion after tumor biopsy
Biological: DNX-2401
Brain infusion of the virus through the cerebellar peduncle
Other Name: Delta-24

Primary Outcome Measures :
  1. Safety, tolerability and toxicity of DNX-2401 injected in the cerebellar peduncle [ Time Frame: 12 weeks after virus injection ]
    The trial will look for hematologic and neurologic toxicity (NCI-CTCAE v 4.03).

Secondary Outcome Measures :
  1. OS12 [ Time Frame: 12 months after virus injection ]
    Overall Survival at 12 months

  2. Images response [ Time Frame: 12 months after virus injection ]
    Complete/partial response in MRI

  3. QoL [ Time Frame: 12 months after virus injection ]
    measure quality of life baseline assessment and any changes over time

  4. Samples collection [ Time Frame: 12 weeks after virus injection ]
    Collect tumor and blood samples for futures molecular and immune studies.

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

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 (aspartate transaminase) and/or ALT (alanine transaminase)> 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-Fraumeni 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03178032

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Clinica Universidad de Navarra
Pamplona, Navarra, Spain, 31190
Sponsors and Collaborators
Clinica Universidad de Navarra, Universidad de Navarra
DNAtrix, Inc.
Alcyone Lifesciences, Inc.
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Principal Investigator: Jaime Gallego, MD, PhD Clinica Universidad de Navarra
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Clinica Universidad de Navarra, Universidad de Navarra
ClinicalTrials.gov Identifier: NCT03178032    
Other Study ID Numbers: D24-DIPG
First Posted: June 6, 2017    Key Record Dates
Last Update Posted: July 16, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: During the trail the results will be presented in scientific meetings. After the trial, a paper will be published by the IP

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Clinica Universidad de Navarra, Universidad de Navarra:
Diffuse intrinsic pontine gliomas
Oncolytic adenovirus
Additional relevant MeSH terms:
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Diffuse Intrinsic Pontine Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Brain Stem Neoplasms
Infratentorial Neoplasms
Brain Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases