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Virus DNX2401 and Temozolomide in Recurrent Glioblastoma (D24GBM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01956734
Recruitment Status : Completed
First Posted : October 8, 2013
Last Update Posted : October 24, 2017
DNAtrix, Inc.
Information provided by (Responsible Party):
Clinica Universidad de Navarra, Universidad de Navarra

Tracking Information
First Submitted Date  ICMJE September 27, 2013
First Posted Date  ICMJE October 8, 2013
Last Update Posted Date October 24, 2017
Actual Study Start Date  ICMJE September 2013
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 7, 2013)
Number of participans with adverse events [ Time Frame: 3 months ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01956734 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 7, 2013)
  • Efficacy of the combination: PFS6 and OS12 [ Time Frame: 12 months ]
    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
  • Tumor response [ Time Frame: 12 months ]
    To assess tumor response using RANO criteria
  • Quality of life [ Time Frame: 18 months ]
    To measure quality of life (QoL) baseline assessment and any changes over time
  • Biological response [ Time Frame: 3 months ]
    To determine immunogenicity, biomarkers and tumor genetics
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Virus DNX2401 and Temozolomide in Recurrent Glioblastoma
Official Title  ICMJE 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
Brief 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. 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.

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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioblastoma Multiforme
  • Recurrent Tumor
Intervention  ICMJE Procedure: DNX2401 and Temozolomide

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

Temozolomide oral 14 days after virus injection.

Study Arms  ICMJE 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.

Intervention: Procedure: DNX2401 and Temozolomide
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: October 7, 2013)
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 2017
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01956734
Other Study ID Numbers  ICMJE D24GBM EudraCT: 2011-005935-21
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Clinica Universidad de Navarra, Universidad de Navarra
Study Sponsor  ICMJE Clinica Universidad de Navarra, Universidad de Navarra
Collaborators  ICMJE DNAtrix, Inc.
Investigators  ICMJE
Principal Investigator: Sonia Tejada, MD, PhD Clinica Universidad de Navarra
PRS Account Clinica Universidad de Navarra, Universidad de Navarra
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP