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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
Sponsor:
Collaborators:
DNAtrix, Inc.
Alcyone Lifesciences, Inc.
Information provided by (Responsible Party):
Clinica Universidad de Navarra, Universidad de Navarra

Tracking Information
First Submitted Date  ICMJE June 3, 2017
First Posted Date  ICMJE June 6, 2017
Last Update Posted Date July 16, 2020
Actual Study Start Date  ICMJE May 26, 2017
Estimated Primary Completion Date January 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 3, 2017)
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 3, 2017)
  • OS12 [ Time Frame: 12 months after virus injection ]
    Overall Survival at 12 months
  • Images response [ Time Frame: 12 months after virus injection ]
    Complete/partial response in MRI
  • QoL [ Time Frame: 12 months after virus injection ]
    measure quality of life baseline assessment and any changes over time
  • Samples collection [ Time Frame: 12 weeks after virus injection ]
    Collect tumor and blood samples for futures molecular and immune studies.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Oncolytic Adenovirus, DNX-2401, for Naive Diffuse Intrinsic Pontine Gliomas
Official Title  ICMJE Phase I Trial of DNX-2401 for Diffuse Intrinsic Pontine Glioma Newly Diagnosed in Pediatric Patients.
Brief Summary Oncolytic adenovirus for pediatric naive DIPG, to be infused after tumor biopsy through the same trajectory in the cerebellar peduncle.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Brainstem Glioma
  • Neoadjuvant Therapy
Intervention  ICMJE Biological: DNX-2401
Brain infusion of the virus through the cerebellar peduncle
Other Name: Delta-24
Study Arms  ICMJE Experimental: single arm treatment DNX-2401
Single arm receiving virus DNX-2401 infusion after tumor biopsy
Intervention: Biological: DNX-2401
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Actual Enrollment  ICMJE
 (submitted: June 3, 2017)
12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 31, 2021
Estimated Primary Completion Date January 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03178032
Other Study ID Numbers  ICMJE D24-DIPG
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
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
Current Responsible Party Clinica Universidad de Navarra, Universidad de Navarra
Original Responsible Party Sonia Tejada, Clinica Universidad de Navarra, Universidad de Navarra, MD
Current Study Sponsor  ICMJE Clinica Universidad de Navarra, Universidad de Navarra
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • DNAtrix, Inc.
  • Alcyone Lifesciences, Inc.
Investigators  ICMJE
Principal Investigator: Jaime Gallego, MD, PhD Clinica Universidad de Navarra
PRS Account Clinica Universidad de Navarra, Universidad de Navarra
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP