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Comparison of Two Dosing Regimens of Temozolomide in Patients With Progressive or Recurrent Glioblastoma (DIRECTOR)

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: NCT00941460
Recruitment Status : Completed
First Posted : July 17, 2009
Last Update Posted : August 15, 2014
Essex Pharma GmbH
Information provided by (Responsible Party):
Prof. Dr. Wolfgang Wick, Heidelberg University

Brief Summary:
For patients with progressive or recurrent glioblastoma there is no standard therapy. One strategy is re-exposure to temozolomide in a higher dose. This increase in dosing can be done by 2 regimens. Aim of this study is to compare these 2 dosing regimens concerning toxicity. In study arm A patients receive temozolomide for one week, followed by a week without temozolomide. In study arm B patients receive temozolomide for three weeks, followed by a week without temozolomide. The regimen that is less toxic will be selected for further evaluations.

Condition or disease Intervention/treatment Phase
Glioblastoma Drug: Temozolomide in both arms Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 105 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Dose-intensified Rechallenge With Temozolomide, One Week On One Week Off Versus Three Weeks On One Week Off in Patients With Progressive or Recurrent Glioblastoma
Study Start Date : September 2009
Actual Primary Completion Date : June 2013
Actual Study Completion Date : June 2013

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: one week on one week off
One week on temozolomide is followed by a week without temozolomide.
Drug: Temozolomide in both arms
initial dose 120 mg/m2 in arm A
Other Name: Temodal

Experimental: three weeks on, one week off
Temozolomide is given over 3 weeks, followed by a week without temozolomide.
Drug: Temozolomide in both arms
initial dose 80 mg/m2 in arm B
Other Name: Temodal

Primary Outcome Measures :
  1. Median time to treatment failure. Treatment failure is reached (i) upon tumor progression as outlined in protocol (ii) if treatment has to be terminated due to toxicity or (iii) if the patient dies for any reason. [ Time Frame: up to one year ]

Secondary Outcome Measures :
  1. progression free survival [ Time Frame: up to two years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Progressive or recurrent glioblastoma documented by MRI no earlier than 180 days after first surgery for glioblastoma and no earlier than 90 days after completion of radiotherapy.
  • Histological diagnosis of glioblastoma
  • Tissue available for the determination of MGMT promoter methylation in the primary tumor or from the recurrent tumor if a patient undergoes a surgical procedure at recurrence prior to study entry.
  • Prior treatment with temozolomide administered concomitantly with radiotherapy and at least for two cycles (5/28) as an adjuvant treatment
  • Informed consent
  • Age 18-80 years
  • Karnofsky performance score > 50%
  • Neutrophil counts > 1 500/µl
  • Platelet counts > 100 000/µl
  • Hemoglobin > 10 g/dl
  • Serum creatinin < 1.5-fold upper normal range
  • ASAT or ALAT < 3-fold upper normal range unless attributed to anticonvulsants
  • Alkaline phosphatase < 3-fold upper normal range
  • Women with childbearing potential must have a negative serum pregnancy test ≤14 days prior to study enrollment
  • Willingness to apply contraception according to local requirements (as stated in patient information)

Exclusion Criteria:

  • Progressive or recurrent glioblastoma documented by MRI earlier than 180 days after first surgery for glioblastoma and earlier than 90 days after completion of radiotherapy.
  • Treatment with any chemotherapy other than temozolomide according to the schedule of the EORTC NCIC trial (Stupp et al. N Engl J Med 2005;352:987-996) except that an adjuvant starting dose of 200 mg/m2 and more than 6 cycles of adjuvant temozolomide are allowed
  • Prior systemic or local treatment with DNA-damaging agents, tyrosine kinase inhibitors or anti-angiogenic agents for any cancer
  • Allergy to or other intolerability of temozolomide
  • Unable to undergo MRI
  • Past medical history of diseases with poor prognosis, e.g. severe coronary heart disease, severe diabetes, immune deficiency, residual deficits after stroke, severe mental retardation
  • HIV infection
  • Pregnancy
  • Breast feeding
  • Treatment within in any other clinical trial parallel to the treatment phase of the current study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00941460

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Landesnervenklinik Wagner-Jauregg
Linz, Austria, 4020
Medical University Vienna, Department of Internal Medicine I
Wien, Austria, 1090
Charite, Department of Neurosurgery
Berlin, Germany, 13353
Knappschaftskrankenhaus, Department of Neurology
Bochum, Germany, 44892
University Hospital Bonn, Department of Neurology
Bonn, Germany, 53105
University Hospital Düsseldorf
Düsseldorf, Germany, 40001
Klinikum der Johann-Wolfgang von Goethe-Universität, Dr. Senckenbergisches Institut für Neuroonkologie, Zentrum für Neurologie und Neurochirurgie
Frankfurt, Germany, 60528
University Hospital Freiburg
Freiburg, Germany, 79106
University Hospital Heidelberg, Department of Neurooncology
Heidelberg, Germany, 69120
Saarland University, Department of Neurosurgery
Homburg/ Saar, Germany, 66421
Klinik für Allgemeine Neurochirurgie
Köln, Germany, 50937
Klinik und Poliklinik für Neurochirurgie
Leipzig, Germany, 04103
Ludwig Maximilians University of Munich , Grosshadern Hospital, Department of Neurosurgery
Munich, Germany, 81377
University of Regensburg, Department of Neurology
Regensburg, Germany, 93053
University Hospital Zurich, Department of Neurology
Zurich, CH, Switzerland, 8091
Centre Hospitalier Universitaire Vaudois and University of Lausanne
Lausanne, Switzerland
Sponsors and Collaborators
Prof. Dr. Wolfgang Wick
Essex Pharma GmbH
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Study Chair: Michael Weller, Prof. Dr. University of Zurich
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Responsible Party: Prof. Dr. Wolfgang Wick, Coordinating Investigator, Heidelberg University Identifier: NCT00941460    
Other Study ID Numbers: DIRECTOR
2008-006871-60 ( EudraCT Number )
ISRCTN68738654 ( Registry Identifier: controlled-trials )
First Posted: July 17, 2009    Key Record Dates
Last Update Posted: August 15, 2014
Last Verified: August 2014
Keywords provided by Prof. Dr. Wolfgang Wick, Heidelberg University:
progressive or recurrent glioblastoma
dose intensification
comparison of two dosing regimens
Additional relevant MeSH terms:
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Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents