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

Glioblastoma Clinical Trial

— DIRECTOR  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00941460
• Other study ID #: DIRECTOR
• Secondary ID: 2008-006871-60IS
• Status: Completed
• Phase: Phase 2
• First received: July 16, 2009
• Last updated: August 13, 2014
• Start date: September 2009
• Est. completion date: June 2013

Study information

• Verified date: August 2014
• Source: Heidelberg University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesAustria: Federal Office for Safety in Health CareSwitzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Drug:
• Temozolomide in both arms
initial dose 120 mg/m2 in arm A
• Temozolomide in both arms
initial dose 80 mg/m2 in arm B

Locations

Country	Name	City	State
Austria	Landesnervenklinik Wagner-Jauregg	Linz
Austria	Medical University Vienna, Department of Internal Medicine I	Wien
Germany	Charite, Department of Neurosurgery	Berlin
Germany	Knappschaftskrankenhaus, Department of Neurology	Bochum
Germany	University Hospital Bonn, Department of Neurology	Bonn
Germany	University Hospital Düsseldorf	Düsseldorf
Germany	Klinikum der Johann-Wolfgang von Goethe-Universität, Dr. Senckenbergisches Institut für Neuroonkologie, Zentrum für Neurologie und Neurochirurgie	Frankfurt
Germany	University Hospital Freiburg	Freiburg
Germany	University Hospital Heidelberg, Department of Neurooncology	Heidelberg
Germany	Saarland University, Department of Neurosurgery	Homburg/ Saar
Germany	Klinik für Allgemeine Neurochirurgie	Köln
Germany	Klinik und Poliklinik für Neurochirurgie	Leipzig
Germany	Ludwig Maximilians University of Munich , Grosshadern Hospital, Department of Neurosurgery	Munich
Germany	University of Regensburg, Department of Neurology	Regensburg
Switzerland	Centre Hospitalier Universitaire Vaudois and University of Lausanne	Lausanne
Switzerland	University Hospital Zurich, Department of Neurology	Zurich	CH

Sponsors (2)

Lead Sponsor	Collaborator
Prof. Dr. Wolfgang Wick	Essex Pharma GmbH

Countries where clinical trial is conducted

Austria,  Germany,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		up to one year	Yes
Secondary	progression free survival		up to two years	No