Comparison of Two Dosing Regimens of Temozolomide in Patients With Progressive or Recurrent Glioblastoma (DIRECTOR)
This study is ongoing, but not recruiting participants.
Sponsor:
Prof. Dr. Wolfgang Wick
Collaborator:
Essex Pharma GmbH
Information provided by (Responsible Party):
Prof. Dr. Wolfgang Wick, University of Heidelberg
ClinicalTrials.gov Identifier:
NCT00941460
First received: July 16, 2009
Last updated: July 6, 2012
Last verified: July 2012
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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 University of Heidelberg:
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 ]
| Estimated Enrollment: | 166 |
| Study Start Date: | September 2009 |
| Estimated Study Completion Date: | August 2013 |
| Estimated Primary Completion Date: | August 2012 (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
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, University of Heidelberg |
| ClinicalTrials.gov Identifier: | NCT00941460 History of Changes |
| Other Study ID Numbers: | DIRECTOR, 2008-006871-60, ISRCTN68738654 |
| Study First Received: | July 16, 2009 |
| Last Updated: | July 6, 2012 |
| Health Authority: | Germany: Federal Institute for Drugs and Medical Devices Austria: Federal Office for Safety in Health Care Switzerland: Swissmedic |
Keywords provided by University of Heidelberg:
|
progressive or recurrent glioblastoma temozolomide dose intensification comparison of two dosing regimens |
Additional relevant MeSH terms:
|
Glioblastoma Astrocytoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial |
Neoplasms, Nerve Tissue Temozolomide Dacarbazine Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 22, 2013