Virus DNX2401 and Temozolomide in Recurrent Glioblastoma
NCT ID: NCT01956734
Last Updated: 2017-10-24
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
31 participants
INTERVENTIONAL
2013-09-30
2017-03-31
Brief Summary
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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.
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.
Detailed Description
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Conditions
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Keywords
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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DNX2401 and Temozolomide
DNX2401: 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.
DNX2401 and Temozolomide
Virus injection in the brain parenchyma after pathology confirmation of recurrent glioblastoma.
Temozolomide oral 14 days after virus injection.
Interventions
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DNX2401 and Temozolomide
Virus injection in the brain parenchyma after pathology confirmation of recurrent glioblastoma.
Temozolomide oral 14 days after virus injection.
Eligibility Criteria
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Inclusion Criteria
* 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.
* 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.
Exclusion Criteria
* 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.
* 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.
18 Years
75 Years
ALL
No
Sponsors
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DNAtrix, Inc.
INDUSTRY
Clinica Universidad de Navarra, Universidad de Navarra
OTHER
Responsible Party
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Principal Investigators
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Sonia Tejada, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Clinica Universidad de Navarra
Locations
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Clinica Universidad de Navarra
Pamplona, Navarre, Spain
Countries
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References
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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.
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.
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.
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.
Related Links
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Hospital where the clinical trial is performed
Other Identifiers
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D24GBM EudraCT: 2011-005935-21
Identifier Type: -
Identifier Source: org_study_id