AzTrials
AzTrials

Glioblastoma MultiformePhase 1D24GBMNCT01956734

Virus DNX2401 and Temozolomide in Recurrent Glioblastoma

A Phase 1 study testing DNX2401 and Temozolomide in people with Glioblastoma Multiforme and Recurrent Tumor, 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
Search all trials

Trial summary

Phase I trial, unicentric, uncontrolled. Intratumoral injection or intramural (into the resected tumor cavity) of DNX2401 into brain tissue will be followed by up to two 28 - day cycles of oral temozolomide (TMZ) in schedule of 7 days on/7 days off to evaluate safety of the combination. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Glioblastoma Multiforme, Recurrent Tumor
What is being tested?
DNX2401 and Temozolomide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
1 siteSpain
Study dates
Sep 2013to Mar 2017
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 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients willing and able to give informed consent and willing to comply with all the protocol procedures.
  • Patient must be, in the investigator opinion, able to comply with all the protocol procedures.
  • Age 18-75 years.
  • Negative pregnant test in case of fertile women.
  • Patient diagnosed GBM in first recurrence after radiotherapy and TMZ. Must have completed at least radiotherapy and one TMZ cycle afterwards.
  • Intraoperative histological verification of recurrence is needed to confirm inclusion.
Show all 10Show fewer
  • Karnofsky Performance Status ≥ 70 before inclusion
  • Lesion considered by the investigator to be resectable or accessible for stereotactic biopsy. Lesion location will allow injection without entrance of virus in the ventricular system.
  • Last TMZ cycle must have been finished at least 4 weeks before entry in the study.
  • Must have adequate renal, bone marrow and liver function.

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.
  • Participation on another clinical trial in the previous 30 days.
  • Previous hypersensitivity to temozolomide or any associated components. Previous serious toxicity to temozolomide.
  • Subjects with immunodeficiency, autoimmune conditions or active hepatitis.
  • Any medical or psychological condition that might interfere with the subject's ability to participate or give informed consent.
  • Tumor with multiple locations, unless all the lesions are considered resectable, or all the lesions except one can be resected, and the last one can be injected; diffuse subependymal spreading or location that would need injection through ventricle.
Show all 10Show fewer
  • Current diagnosis of other cancer except in situ cervical cancer, basal or squamous cell carcinoma of the skin. Patients with a history of another cancer remain eligible if they are cancer free for at least three years.
  • 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.
  • Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) > 3 times over normal laboratory level.

Trial locations and contacts

1 site in 1 country.

Spain1 site

  • Clinica Universidad de Navarra

    Pamplona, Navarre, 31008

Other trials in Spain

About this study

Official title: Phase I Trial of Combination of DNX-2401 (Formerly Named Delta-24-RGD) Oncolytic Adenovirus With a Short Course of Temozolomide for Treatment of Glioblastoma at First Recurrent

Phase I trial, unicentric, uncontrolled. Intratumoral injection or intramural (into the resected tumor cavity) of DNX2401 into brain tissue will be followed by up to two 28 - day cycles of oral temozolomide (TMZ) in schedule of 7 days on/7 days off to evaluate safety of the combination. Completion of two full cycles of TMZ will be dependent upon tolerance and toxicity.

The rationale in using the virus with chemotherapy begins with the lessons learned in many clinical trials in glioblastoma (GBM) about both the great difficulty of treating this disease with monotherapy and the limitations of the therapeutic virus. The best clinical results in recent years have been achieved with combinations of multiple therapeutics efforts, including, maximum resection and chemotherapy, immunotherapy and targeted therapies.

Read more

There are very strong preclinical data about the synergy of DNX-2401 and TMZ proposed in our trial design. The dose-dense schemes of TMZ like the one we will use, have been developed with the aim to saturate o6-methylguanine-DNA-methyltransferase (MGMT). The published results to date have shown reasonable toxicity albeit with modest efficacy' these schemes are now in phase III trials. In addition, autophagy triggered by TMZ could help viral replication in the tumor cells 11.

The last argument in favor of this virus + TMZ combination is the proved efficacy in killing GBM tumor stem cells. In vitro and animals models have shown this combination is much more effective that any of the treatments alone against GBM stem cells and the tumors derived from them.

Read the detailed description

DNX2401 will be injected after stereotactic biopsy reveals intraoperative pathology confirming the presence of recurrent glioblastoma. The injection will be either intratumoral or intramural with injections throughout the post-resection cavity.

Being tested
DNX2401 and Temozolomide
Keywords
glioblastoma, first recurrence, temozolomide
Medical subject headings
Glioblastoma, Recurrence

What participants receive

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

  • DNX2401 and TemozolomideProcedure or surgery

    Virus injection in the brain parenchyma after pathology confirmation of recurrent glioblastoma.

    Temozolomide oral 14 days after virus injection.

Study groups in NCT01956734
Study groupRoleWhat they receive
DNX2401 and TemozolomideExperimentalDNX2401: Virus injection in the brain parenchyma. Total dose will be 3x1010 vp suspended in 1 ml for all cases. Temozolomide: 14 (window 14-28 days) days after the virus injection, patients will begin therapy with temozolomide in a dose of 150mg/m2 in days 1-7 and 15 -21 of a 28 days cycle, (dose dense scheme 7 days on, 7 days off), until a maximum of 2 x 28 days cycles in absence of toxicity.
Receives: Procedure: DNX2401 and Temozolomide

What is being measured

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

  1. Number of participans with adverse events

    Tolerance of the combination of DNX-2401 and temozolomide will be evaluated through neurological and hematological status. Any toxicity will be graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTCAE) version 4.03.

    Measured: 3 months

Secondary outcomes (4)

  1. Efficacy of the combination: PFS6 and OS12

    To determine, using the Revised Assessment in Neuro-Oncology (RANO) criteria, time to disease progression, progression-free survival at 6 months (PFS6), median progression-free survival, overall survival at 12 months (OS12) and median overall survival following intratumoral or intramural injection of DNX-2401 and two cycles of temozolomide

    Measured: 12 months

  2. Tumor response

    To assess tumor response using RANO criteria

    Measured: 12 months

  3. Quality of life

    To measure quality of life (QoL) baseline assessment and any changes over time

    Measured: 18 months

  4. Biological response

    To determine immunogenicity, biomarkers and tumor genetics

    Measured: 3 months

Timeline

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

  1. First posted8 Oct 2013 (estimated)
  2. Study startSep 2013
  3. Primary completionDec 2015
  4. Study completionMar 2017

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
31 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01956734
Sponsor's protocol ID
D24GBM EudraCT: 2011-005935-21
Acronym
D24GBM
Status last verified
Jun 2017
First submitted
27 Sep 2013
Last updated
24 Oct 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Fueyo J, Gomez-Manzano C, Alemany R, Lee PS, McDonnell TJ, Mitlianga P, Shi YX, Levin VA, Yung WK, Kyritsis AP. A mutant oncolytic adenovirus targeting the Rb pathway produces anti-glioma effect in vivo. Oncogene. 2000 Jan 6;19(1):2-12. doi: 10.1038/sj.onc.1203251.

    PubMed 10644974

  • Jiang H, Gomez-Manzano C, Lang FF, Alemany R, Fueyo J. Oncolytic adenovirus: preclinical and clinical studies in patients with human malignant gliomas. Curr Gene Ther. 2009 Oct;9(5):422-7. doi: 10.2174/156652309789753356.

    PubMed 19860656

  • 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

  • Jiang H, Alonso MM, Gomez-Manzano C, Piao Y, Fueyo J. Oncolytic viruses and DNA-repair machinery: overcoming chemoresistance of gliomas. Expert Rev Anticancer Ther. 2006 Nov;6(11):1585-92. doi: 10.1586/14737140.6.11.1585.

    PubMed 17134363

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing DNX2401 and Temozolomide in people with Glioblastoma Multiforme and Recurrent Tumor, 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 10 inclusion and 10 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 24 Oct 2017. 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?

Number of participans with adverse events (time frame: 3 months). 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 NCT01956734, which also lists 4 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 24 Oct 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in