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

Primary Purpose

Glioblastoma

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Temozolomide in both arms

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring progressive or recurrent glioblastoma, temozolomide, dose intensification, comparison of two dosing regimens

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Landesnervenklinik Wagner-Jauregg
Medical University Vienna, Department of Internal Medicine I
Charite, Department of Neurosurgery
Knappschaftskrankenhaus, Department of Neurology
University Hospital Bonn, Department of Neurology
University Hospital Düsseldorf
Klinikum der Johann-Wolfgang von Goethe-Universität, Dr. Senckenbergisches Institut für Neuroonkologie, Zentrum für Neurologie und Neurochirurgie
University Hospital Freiburg
University Hospital Heidelberg, Department of Neurooncology
Saarland University, Department of Neurosurgery
Klinik für Allgemeine Neurochirurgie
Klinik und Poliklinik für Neurochirurgie
Ludwig Maximilians University of Munich , Grosshadern Hospital, Department of Neurosurgery
University of Regensburg, Department of Neurology
University Hospital Zurich, Department of Neurology
Centre Hospitalier Universitaire Vaudois and University of Lausanne

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

one week on one week off

three weeks on, one week off

Arm Description

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

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

Outcomes

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.

Secondary Outcome Measures

progression free survival

Full Information

NCT ID

NCT00941460

First Posted

July 16, 2009

Last Updated

August 13, 2014

Sponsor

Prof. Dr. Wolfgang Wick

Collaborators

Essex Pharma GmbH

1. Study Identification

Unique Protocol Identification Number

NCT00941460

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2014

Overall Recruitment Status

Completed

Study Start Date

September 2009 (undefined)

Primary Completion Date

June 2013 (Actual)

Study Completion Date

June 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Prof. Dr. Wolfgang Wick

Collaborators

Essex Pharma GmbH

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

105 (Actual)

8. Arms, Groups, and Interventions

Arm Title

one week on one week off

Arm Type

Experimental

Arm Description

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

Arm Title

three weeks on, one week off

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Temozolomide in both arms

Other Intervention Name(s)

Temodal

Intervention Description

initial dose 120 mg/m2 in arm A

Intervention Type

Drug

Intervention Name(s)

Temozolomide in both arms

Other Intervention Name(s)

Temodal

Intervention Description

initial dose 80 mg/m2 in arm B

Primary Outcome Measure Information:

Title

Time Frame

up to one year

Secondary Outcome Measure Information:

Title

progression free survival

Time Frame

up to two years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Weller, Prof. Dr.

Organizational Affiliation

University of Zurich

Official's Role

Study Chair

Facility Information:

Facility Name

Landesnervenklinik Wagner-Jauregg

City

Linz

ZIP/Postal Code

4020

Country

Austria

Facility Name

Medical University Vienna, Department of Internal Medicine I

City

Wien

ZIP/Postal Code

1090

Country

Austria

Facility Name

Charite, Department of Neurosurgery

City

Berlin

ZIP/Postal Code

13353

Country

Germany

Facility Name

Knappschaftskrankenhaus, Department of Neurology

City

Bochum

ZIP/Postal Code

44892

Country

Germany

Facility Name

University Hospital Bonn, Department of Neurology

City

Bonn

ZIP/Postal Code

53105

Country

Germany

Facility Name

University Hospital Düsseldorf

City

Düsseldorf

ZIP/Postal Code

40001

Country

Germany

Facility Name

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

City

Frankfurt

ZIP/Postal Code

60528

Country

Germany

Facility Name

University Hospital Freiburg

City

Freiburg

ZIP/Postal Code

79106

Country

Germany

Facility Name

University Hospital Heidelberg, Department of Neurooncology

City

Heidelberg

ZIP/Postal Code

69120

Country

Germany

Facility Name

Saarland University, Department of Neurosurgery

City

Homburg/ Saar

ZIP/Postal Code

66421

Country

Germany

Facility Name

Klinik für Allgemeine Neurochirurgie

City

Köln

ZIP/Postal Code

50937

Country

Germany

Facility Name

Klinik und Poliklinik für Neurochirurgie

City

Leipzig

ZIP/Postal Code

04103

Country

Germany

Facility Name

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

City

Munich

ZIP/Postal Code

81377

Country

Germany

Facility Name

University of Regensburg, Department of Neurology

City

Regensburg

ZIP/Postal Code

93053

Country

Germany

Facility Name

University Hospital Zurich, Department of Neurology

City

Zurich

State/Province

ZIP/Postal Code

8091

Country

Switzerland

Facility Name

Centre Hospitalier Universitaire Vaudois and University of Lausanne

City

Lausanne

Country

Switzerland

12. IPD Sharing Statement

Learn more about this trial

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

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