NCT03178032

Brief Summary

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
12

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started May 2017

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 26, 2017

Completed
8 days until next milestone

First Submitted

Initial submission to the registry

June 3, 2017

Completed
3 days until next milestone

First Posted

Study publicly available on registry

June 6, 2017

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 31, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 31, 2021

Completed
Last Updated

April 6, 2023

Status Verified

April 1, 2023

Enrollment Period

3.7 years

First QC Date

June 3, 2017

Last Update Submit

April 5, 2023

Conditions

Brainstem GliomaNeoadjuvant Therapy

Keywords

Diffuse intrinsic pontine gliomasOncolytic adenovirus

Outcome Measures

Primary Outcomes (1)

  • Safety, tolerability and toxicity of DNX-2401 injected in the cerebellar peduncle

    The trial will look for hematologic and neurologic toxicity (NCI-CTCAE v 4.03).

    12 weeks after virus injection

Secondary Outcomes (4)

  • OS12

    12 months after virus injection

  • Images response

    12 months after virus injection

  • QoL

    12 months after virus injection

  • Samples collection

    12 weeks after virus injection

Study Arms (1)

single arm treatment DNX-2401

EXPERIMENTAL

Single arm receiving virus DNX-2401 infusion after tumor biopsy

Biological: DNX-2401

Interventions

DNX-2401BIOLOGICAL

Brain infusion of the virus through the cerebellar peduncle

Also known as: Delta-24
single arm treatment DNX-2401

Eligibility Criteria

Age1 Year - 18 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Informed consent OF PATIENT OR PARENTS
  • Patient must be, in the investigator opinion, able to comply with all the protocol procedures.
  • Age 1 - 18 years
  • 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.
  • Patient newly diagnosed of DIPG in MRI
  • Lesion considered by the investigator to be accessible for stereotactic biopsy. Lesion location will allow injection without entrance of virus in the ventricular system.
  • No previous treatment for DIPG

You may not qualify if:

  • Investigational medication in the previous 30 days.
  • Subjects with immunodeficiency, autoimmune conditions or active hepatitis.
  • 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.
  • Tumor with multiple locations or doubt in MRI of a DIPG.
  • 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.
  • Severe bone marrow hypoplasia.
  • AST (aspartate transaminase) and/or ALT (alanine transaminase)\> 3 times over upper normal laboratory level
  • Neutrophils \< 1 x 109/L
  • Thrombocytes ≤ 100 x 109/L
  • Hemoglobin \< 9g/dl
  • \. Patients with Li-Fraumeni Syndrome or with a known germ line deficit in the retinoblastoma gene or its related pathways.
  • \. 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Clinica Universidad de Navarra

Pamplona, Navarre, 31190, Spain

Location

Related Publications (5)

  • Alonso MM, Gomez-Manzano C, Bekele BN, Yung WK, Fueyo J. Adenovirus-based strategies overcome temozolomide resistance by silencing the O6-methylguanine-DNA methyltransferase promoter. Cancer Res. 2007 Dec 15;67(24):11499-504. doi: 10.1158/0008-5472.CAN-07-5312.

    PMID: 18089777RESULT

  • Jansen MH, Veldhuijzen van Zanten SE, Sanchez Aliaga E, Heymans MW, Warmuth-Metz M, Hargrave D, van der Hoeven EJ, Gidding CE, de Bont ES, Eshghi OS, Reddingius R, Peeters CM, Schouten-van Meeteren AY, Gooskens RH, Granzen B, Paardekooper GM, Janssens GO, Noske DP, Barkhof F, Kramm CM, Vandertop WP, Kaspers GJ, van Vuurden DG. Survival prediction model of children with diffuse intrinsic pontine glioma based on clinical and radiological criteria. Neuro Oncol. 2015 Jan;17(1):160-6. doi: 10.1093/neuonc/nou104. Epub 2014 Jun 5.

    PMID: 24903904RESULT

  • Jiang H, Gomez-Manzano C, Aoki H, Alonso MM, Kondo S, McCormick F, Xu J, Kondo Y, Bekele BN, Colman H, Lang FF, Fueyo J. Examination of the therapeutic potential of Delta-24-RGD in brain tumor stem cells: role of autophagic cell death. J Natl Cancer Inst. 2007 Sep 19;99(18):1410-4. doi: 10.1093/jnci/djm102. Epub 2007 Sep 11.

    PMID: 17848677RESULT

  • Gallego Perez-Larraya J, Garcia-Moure M, Labiano S, Patino-Garcia A, Dobbs J, Gonzalez-Huarriz M, Zalacain M, Marrodan L, Martinez-Velez N, Puigdelloses M, Laspidea V, Astigarraga I, Lopez-Ibor B, Cruz O, Oscoz Lizarbe M, Hervas-Stubbs S, Alkorta-Aranburu G, Tamayo I, Tavira B, Hernandez-Alcoceba R, Jones C, Dharmadhikari G, Ruiz-Moreno C, Stunnenberg H, Hulleman E, van der Lugt J, Idoate MA, Diez-Valle R, Esparragosa Vazquez I, Villalba M, de Andrea C, Nunez-Cordoba JM, Ewald B, Robbins J, Fueyo J, Gomez-Manzano C, Lang FF, Tejada S, Alonso MM. Oncolytic DNX-2401 Virus for Pediatric Diffuse Intrinsic Pontine Glioma. N Engl J Med. 2022 Jun 30;386(26):2471-2481. doi: 10.1056/NEJMoa2202028.

    PMID: 35767439DERIVED

  • Martinez-Velez N, Garcia-Moure M, Marigil M, Gonzalez-Huarriz M, Puigdelloses M, Gallego Perez-Larraya J, Zalacain M, Marrodan L, Varela-Guruceaga M, Laspidea V, Aristu JJ, Ramos LI, Tejada-Solis S, Diez-Valle R, Jones C, Mackay A, Martinez-Climent JA, Garcia-Barchino MJ, Raabe E, Monje M, Becher OJ, Junier MP, El-Habr EA, Chneiweiss H, Aldave G, Jiang H, Fueyo J, Patino-Garcia A, Gomez-Manzano C, Alonso MM. The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models. Nat Commun. 2019 May 28;10(1):2235. doi: 10.1038/s41467-019-10043-0.

    PMID: 31138805DERIVED

Study Officials

  • Jaime Gallego, MD, PhD

    Clinica Universidad de Navarra

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 3, 2017

First Posted

June 6, 2017

Study Start

May 26, 2017

Primary Completion

January 31, 2021

Study Completion

January 31, 2021

Last Updated

April 6, 2023

Record last verified: 2023-04

Data Sharing

IPD Sharing
Will share

During the trail the results will be presented in scientific meetings. After the trial, a paper will be published by the IP

Locations

ES(1)