Clinical trial NCT00941460: Comparison of Two Dosing Regimens of Temozolomide in Patients With Progressive or Recurrent Glioblastoma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma
Keywords: progressive or recurrent glioblastoma
temozolomide
dose intensification
comparison of two dosing regimens
Lead sponsor: Heidelberg University
Sponsor class: OTHER
Collaborators: name: Essex Pharma GmbH
First posted: 2009-07-17
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: 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.
timeFrame: up to one year
Secondary outcomes:
measure: progression free survival
timeFrame: up to two years
Other outcomes:
Locations:
city: Linz
country: Austria
facility: Landesnervenklinik Wagner-Jauregg
city: Wien
country: Austria
facility: Medical University Vienna, Department of Internal Medicine I
city: Berlin
country: Germany
facility: Charite, Department of Neurosurgery
city: Bochum
country: Germany
facility: Knappschaftskrankenhaus, Department of Neurology
city: Bonn
country: Germany
facility: University Hospital Bonn, Department of Neurology
city: Düsseldorf
country: Germany
facility: University Hospital Düsseldorf
city: Frankfurt
country: Germany
facility: Klinikum der Johann-Wolfgang von Goethe-Universität, Dr. Senckenbergisches Institut für Neuroonkologie, Zentrum für Neurologie und Neurochirurgie
city: Freiburg
country: Germany
facility: University Hospital Freiburg
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg, Department of Neurooncology
city: Homburg/ Saar
country: Germany
facility: Saarland University, Department of Neurosurgery
city: Köln
country: Germany
facility: Klinik für Allgemeine Neurochirurgie
city: Leipzig
country: Germany
facility: Klinik und Poliklinik für Neurochirurgie
city: Munich
country: Germany
facility: Ludwig Maximilians University of Munich , Grosshadern Hospital, Department of Neurosurgery
city: Regensburg
country: Germany
facility: University of Regensburg, Department of Neurology
city: Zurich
country: Switzerland
facility: University Hospital Zurich, Department of Neurology
state: CH
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois and University of Lausanne
Study officials:
affiliation: University of Zurich
name: Michael Weller, Prof. Dr.
role: STUDY_CHAIR
References: