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

NCT00941460 | Completed Phase 2

• 3 other identifiers: DIRECTOR2008-006871-60ISRCTN68738654
• Study Type: interventional
• Target: 105
• Locations: 3 countries
• Sites: 16

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.

Conditions

Glioblastoma

Keywords

progressive or recurrent glioblastoma; temozolomide; dose intensification; comparison of two dosing regimens

Outcome Measures

Primary Outcomes (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.

  up to one year

Secondary Outcomes (1)

• progression free survival

  up to two years

Study Arms (2)

one week on one week off

EXPERIMENTAL

One week on temozolomide is followed by a week without temozolomide.

Drug: Temozolomide in both arms

three weeks on, one week off

EXPERIMENTAL

Temozolomide is given over 3 weeks, followed by a week without temozolomide.

Drug: Temozolomide in both arms

Interventions

Temozolomide in both arms DRUG

initial dose 120 mg/m2 in arm A

Also known as: Temodal

one week on one week off

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Prof. Dr. Wolfgang Wick: lead
• Essex Pharma GmbH: collaborator

Study Sites (16)

Landesnervenklinik Wagner-Jauregg

Linz, 4020, Austria

Location

Medical University Vienna, Department of Internal Medicine I

Vienna, 1090, Austria

Location

Charite, Department of Neurosurgery

Berlin, 13353, Germany

Location

Knappschaftskrankenhaus, Department of Neurology

Bochum, 44892, Germany

Location

University Hospital Bonn, Department of Neurology

Bonn, 53105, Germany

Location

Klinik für Allgemeine Neurochirurgie

Cologne, 50937, Germany

Location

University Hospital Düsseldorf

Düsseldorf, 40001, Germany

Location

Klinikum der Johann-Wolfgang von Goethe-Universität, Dr. Senckenbergisches Institut für Neuroonkologie, Zentrum für Neurologie und Neurochirurgie

Frankfurt, 60528, Germany

Location

University Hospital Freiburg

Freiburg im Breisgau, 79106, Germany

Location

University Hospital Heidelberg, Department of Neurooncology

Heidelberg, 69120, Germany

Location

Saarland University, Department of Neurosurgery

Homburg/ Saar, 66421, Germany

Location

Klinik und Poliklinik für Neurochirurgie

Leipzig, 04103, Germany

Location

Ludwig Maximilians University of Munich , Grosshadern Hospital, Department of Neurosurgery

Munich, 81377, Germany

Location

University of Regensburg, Department of Neurology

Regensburg, 93053, Germany

Location

University Hospital Zurich, Department of Neurology

Zurich, CH, 8091, Switzerland

Location

Centre Hospitalier Universitaire Vaudois and University of Lausanne

Lausanne, Switzerland

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Michael Weller, Prof. Dr.

  University of Zurich

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Coordinating Investigator

Study Record Dates

• First Submitted: July 16, 2009
• First Posted: July 17, 2009
• Study Start: September 1, 2009
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: August 15, 2014

Record last verified: 2014-08

Locations

CH (2); DE (12); AU (2)