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Brainstem GliomaPhase 1NCT03178032

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

A Phase 1 study testing DNX-2401 in people with Brainstem Glioma and Neoadjuvant Therapy, run by Clinica Universidad de Navarra, Universidad de Navarra at 1 site in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 1 year to 18 years
Conditions the study is for
Brainstem Glioma, Neoadjuvant Therapy
What is being tested?
DNX-2401
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteSpain
Study dates
26 May 2017to 31 Jan 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
  • Lansky Performance Status ≥ 70 before inclusion
  • 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

Who cannot join

  • 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)].
  • 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.
Show all 13Show fewer
  • 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
  • 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.

Trial locations and contacts

1 site in 1 country.

Spain1 site

  • Clinica Universidad de Navarra

    Pamplona, Navarre, 31190

Other trials in Spain

About this study

Official title: Phase I Trial of DNX-2401 for Diffuse Intrinsic Pontine Glioma Newly Diagnosed in Pediatric Patients.

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

Read the 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.

Being tested
DNX-2401
Keywords
Diffuse intrinsic pontine gliomas, Oncolytic adenovirus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DNX-2401Biological

    Also called Delta-24

    Brain infusion of the virus through the cerebellar peduncle

Study groups in NCT03178032
Study groupRoleWhat they receive
single arm treatment DNX-2401ExperimentalSingle arm receiving virus DNX-2401 infusion after tumor biopsy
Receives: Biological: DNX-2401

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: 12 weeks after virus injection

Secondary outcomes (4)

  1. OS12

    Overall Survival at 12 months

    Measured: 12 months after virus injection

  2. Images response

    Complete/partial response in MRI

    Measured: 12 months after virus injection

  3. QoL

    measure quality of life baseline assessment and any changes over time

    Measured: 12 months after virus injection

  4. Samples collection

    Collect tumor and blood samples for futures molecular and immune studies.

    Measured: 12 weeks after virus injection

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jun 2017
  2. Study start26 May 2017
  3. Primary completion31 Jan 2021
  4. Study completion31 Jan 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03178032
Sponsor's protocol ID
D24-DIPG
Status last verified
Apr 2023
First submitted
3 Jun 2017
Last updated
6 Apr 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: During the trail the results will be presented in scientific meetings. After the trial, a paper will be published by the IP

Publications

  • 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.

    PubMed 18089777

  • 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.

    PubMed 24903904

  • 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.

    PubMed 17848677

  • 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.

    PubMed 35767439

  • 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.

    PubMed 31138805

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing DNX-2401 in people with Brainstem Glioma and Neoadjuvant Therapy, run by Clinica Universidad de Navarra, Universidad de Navarra at 1 site in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety, tolerability and toxicity of DNX-2401 injected in the cerebellar peduncle (time frame: 12 weeks after virus injection). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03178032, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2023.

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