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

This study has been completed.
Sponsor:
Collaborator:
Essex Pharma GmbH
Information provided by (Responsible Party):
Prof. Dr. Wolfgang Wick, Heidelberg University
ClinicalTrials.gov Identifier:
NCT00941460
First received: July 16, 2009
Last updated: August 13, 2014
Last verified: August 2014
  Purpose

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 Intervention Phase
Glioblastoma
Drug: Temozolomide in both arms
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Heidelberg University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • progression free survival [ Time Frame: up to two years ] [ Designated as safety issue: No ]

Enrollment: 105
Study Start Date: September 2009
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00941460

Locations
Austria
Landesnervenklinik Wagner-Jauregg
Linz, Austria, 4020
Medical University Vienna, Department of Internal Medicine I
Wien, Austria, 1090
Germany
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
Switzerland
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
Investigators
Study Chair: Michael Weller, Prof. Dr. University of Zurich
  More Information

No publications provided

Responsible Party: Prof. Dr. Wolfgang Wick, Coordinating Investigator, Heidelberg University
ClinicalTrials.gov Identifier: NCT00941460     History of Changes
Other Study ID Numbers: DIRECTOR, 2008-006871-60, ISRCTN68738654
Study First Received: July 16, 2009
Last Updated: August 13, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Austria: Federal Office for Safety in Health Care
Switzerland: Swissmedic

Keywords provided by Heidelberg University:
progressive or recurrent glioblastoma
temozolomide
dose intensification
comparison of two dosing regimens

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Dacarbazine
Temozolomide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014