- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03178032
Oncolytic Adenovirus, DNX-2401, for Naive Diffuse Intrinsic Pontine Gliomas
April 5, 2023 updated by: Clinica Universidad de Navarra, Universidad de Navarra
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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
Interventional
Enrollment (Actual)
12
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Navarra
-
Pamplona, Navarra, Spain, 31190
- Clinica Universidad de Navarra
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
1 year to 18 years (Child, Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: single arm treatment DNX-2401
Single arm receiving virus DNX-2401 infusion after tumor biopsy
|
Brain infusion of the virus through the cerebellar peduncle
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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).
|
12 weeks after virus injection
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
OS12
Time Frame: 12 months after virus injection
|
Overall Survival at 12 months
|
12 months after virus injection
|
Images response
Time Frame: 12 months after virus injection
|
Complete/partial response in MRI
|
12 months after virus injection
|
QoL
Time Frame: 12 months after virus injection
|
measure quality of life baseline assessment and any changes over time
|
12 months after virus injection
|
Samples collection
Time Frame: 12 weeks after virus injection
|
Collect tumor and blood samples for futures molecular and immune studies.
|
12 weeks after virus injection
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Jaime Gallego, MD, PhD, Clinica Universidad de Navarra
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 26, 2017
Primary Completion (Actual)
January 31, 2021
Study Completion (Actual)
January 31, 2021
Study Registration Dates
First Submitted
June 3, 2017
First Submitted That Met QC Criteria
June 3, 2017
First Posted (Actual)
June 6, 2017
Study Record Updates
Last Update Posted (Actual)
April 6, 2023
Last Update Submitted That Met QC Criteria
April 5, 2023
Last Verified
April 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Brain Neoplasms
- Central Nervous System Neoplasms
- Nervous System Neoplasms
- Brain Stem Neoplasms
- Infratentorial Neoplasms
- Glioma
- Diffuse Intrinsic Pontine Glioma
Other Study ID Numbers
- D24-DIPG
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
During the trail the results will be presented in scientific meetings.
After the trial, a paper will be published by the IP
Drug and device information, study documents
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Neoadjuvant Therapy
-
Saint Petersburg State Budgetary Healthcare Institution...Active, not recruitingThe Neoadjuvant TherapyRussian Federation
-
Hongqian GuoActive, not recruiting
-
Mayo ClinicCompletedBreast Cancer | Chemotherapy | Neoadjuvant Therapy | Hormone Replacement TherapyUnited States
-
Shandong UniversityUnknownBreast Neoplasms | Neoadjuvant TherapyChina
-
Wuhan Union Hospital, ChinaRecruitingBreast Cancer | Neoadjuvant TherapyChina
-
Lumicell, Inc.National Cancer Institute (NCI); Massachusetts General HospitalTerminatedBreast Cancer | Neoadjuvant TherapyUnited States
-
Oxford University Hospitals NHS TrustUniversity of OxfordCompleted
-
Cancer Institute and Hospital, Chinese Academy...Chinese Academy of Medical Sciences Cancer Hospital,Shanxi Center; Chinese... and other collaboratorsNot yet recruitingBreast Cancer | Neoadjuvant TherapyChina
-
Zhejiang Cancer HospitalUnknown
-
Blokhin's Russian Cancer Research CenterRecruitingBreast Cancer | Neoadjuvant Endocrine TherapyRussian Federation
Clinical Trials on DNX-2401
-
M.D. Anderson Cancer CenterDNAtrix, Inc.RecruitingRecurrent Glioblastoma | Recurrent Malignant Glioma | Recurrent Gliosarcoma | Recurrent Anaplastic Astrocytoma | IDH1 wt AlleleUnited States
-
DNAtrix, Inc.CompletedCentral Nervous System Diseases | Brain CancerUnited States
-
Clinica Universidad de Navarra, Universidad de...DNAtrix, Inc.Terminated
-
DNAtrix, Inc.CompletedGlioblastoma or GliosarcomaUnited States
-
DNAtrix, Inc.Merck Sharp & Dohme LLCCompletedNervous System Diseases | Glioma | Glioblastoma | Neuroectodermal Tumors | Brain Cancer | Gliosarcoma | Brain Neoplasm | Malignant Brain Tumor | Neoplasm, Neuroepithelial | Neoplasm by Histologic Type | Neoplasm, Nerve TissueUnited States, Canada
-
DNAtrix, Inc.H. Lee Moffitt Cancer Center and Research InstituteSuspendedMelanoma | Sarcoma | Breast Cancer | Gastric Cancer | Colorectal Cancer | Gastrointestinal Stromal Tumors | Periampullary Cancer | Liver Metastases | Renal Cell Cancer | Liver Metastasis Colon Cancer | Squamous Cell CarcinomaUnited States