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Virus DNX2401 and Temozolomide in Recurrent Glioblastoma

Study Purpose

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. 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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

 No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

 Interventional
Eligible Ages 18 Years - 75 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion criteria:

  • - 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.
  • - 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:

  • - 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.
  • - 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 Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

 NCT01956734
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

 Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

 Clinica Universidad de Navarra, Universidad de Navarra
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

 Sonia Tejada, MD, PhD
Principal Investigator Affiliation Clinica Universidad de Navarra
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

 Other, Industry
Overall Status Completed
Countries Spain
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

 Glioblastoma Multiforme, Recurrent Tumor
Study Website: View Trial Website
Additional Details

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.

Arms & Interventions

Arms

Experimental: 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.

Interventions

Procedure: - DNX2401 and Temozolomide

Virus injection in the brain parenchyma after pathology confirmation of recurrent glioblastoma. Temozolomide oral 14 days after virus injection.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Clinica Universidad de Navarra, Pamplona, Navarra, Spain

Status

Address

Clinica Universidad de Navarra

Pamplona, Navarra, 31008

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