Phase III Trial of Primary Radio- or Chemotherapy in Malignant Astrocytoma of the Elderly

NCT ID: NCT01502241

Last Updated: 2011-12-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 412 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-01-31
• Study Completion Date: 2011-11-30

Brief Summary

The study aims to optimize the treatment of elderly subjects (> 65) with anaplastic astrocytoma and glioblastoma. Current treatment policies tend to be no more than palliative. There is no consensus as to how radical the surgery should be. Involved-field radiotherapy is the treatment most likely to be accepted apart from supportive and palliative measures. The role of chemotherapy is barely defined. Study data available to date does not suggest that this patient population would benefit from combined radiochemotherapy. The aim of the study is to verify the hypothesis that first-line chemotherapy with one week on/one week off temozolomide is not inferior to extended-field radiotherapy in the first-line treatment of anaplastic astrocytoma and glioblastoma in the elderly (> 65 age group). The primary endpoint is median survival, as life expectancy is limited to several months. Secondary endpoints are response rates in both arms (CR, PR, MacDonald et al. 1990), median progression-free survival, 1-year and 2-year survival rates, definition of MGMT as molecular genetic prognostic or predictive markers, and quality of life. Theoretically, it should be possible to preserve quality of life in the first-line chemotherapy arm of the study.

Detailed Description

This study is a prospective, randomized Phase III intervention study. Following histological documentation of the diagnosis by biopsy or resection of an anaplastic astrocytoma or glioblastoma, patients will be randomized either to receive postoperative extended-field radiotherapy (arm A) or to receive postoperative chemotherapy with temozolomide (arm B). Randomization will be done for all sites at the CRO, Alcedis GmbH.

For patients intending to participate in the study, the procedure is as follows:

• Request a reference neuropathological review from the brain tumor reference center in Bonn (Prof. Dr. G. Reifenberger) through the local neuropathology department. This review need not be present at randomization because anaplastic astrocytoma and glioblastoma cases are eligible
• Contact: Prof. Dr. W. Wick, Dep. Neurooncology, National Center for Tumor Diseases and Neurology Clinic, University of Heidelberg, wolfgang.wick@med.uni-heidelberg.de or CRO: Alcedis, Giessen at Alcedis GmbH, I. Helm, Winchester Str. 2, 35394 Gießen, Tel.: 0641 944360, Fax: 0641 94436 70, E-mail: ihe@alcedis.de
• Provide written confirmation that the patient signed the ethics committee-approved consent form
• Submit the registration form and a copy of the EORTC-QLQ given in Annexes

In subjects with progressive or recurrent disease, the investigating site will verify whether specific tumor treatment is justified. If yes, chemotherapy with temozolomide is recommended in arm A, possibly after further surgery. Subjects in arm B will receive radiotherapy, possible after further surgery. As all-cause mortality is the primary endpoint, all therapeutic measures following first-line therapy should be documented.

If study treatment is discontinued (first-line therapy) because of progressive disease or if progression occurs after completion of study treatment, the pertinent images should be submitted to the reference center for neuroradiology in Tübingen for reference review.

The treatment modalities employed in the study are chemotherapeutic and radiotherapeutic procedures licensed in the Federal Republic of Germany for use in human subjects. Temozolomide is currently licensed for treating subjects with recurrent disease and since 2006 in newly diagnosed glioblastoma together with radiotherapy. The time allotted for the individual treatment sections is 6 weeks for radiotherapy, while chemotherapy will be continued until progression or unacceptable adverse effects occur. The precise chemotherapy sequence is shown in the protocol. The criteria for withdrawal from the study are defined in in the protocol. Four years is the period scheduled for recruiting all patients.

Conditions

Glioblastoma; Anaplastic Astrocytoma

Keywords

elderly; brain tumors; MGMT; chemotherapy; Newly diagnosed; patients > 65 years

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Radiotherapy

6 weeks standard partial brain treatment.

Group Type: ACTIVE_COMPARATOR

Radiotherapy of the partial brain.

Intervention Type: RADIATION

60 Gy in 30 fractions à 2 Gy.

Temozolomide

Temozolomide in a one week on/one week off schedule per Wick et al. 2004 and A. Wick et al. 2007

Group Type: EXPERIMENTAL

Temozolomide

Intervention Type: DRUG

100 mg/m2 per day on seven out of fourteen days.

Interventions

Temozolomide

100 mg/m2 per day on seven out of fourteen days.

Intervention Type: DRUG

Radiotherapy of the partial brain.

60 Gy in 30 fractions à 2 Gy.

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed supratentorial anaplastic astrocytoma or glioblastoma
• Age > 65
• Karnofsky performance score > 60%
• Neutrophilic granulocyte count > 1500/µl
• Platelet count > 100 000/µl
• Hemoglobin > 10 g/dl
• Serum creatinine < 1.5 times the lab's upper normal limit
• AST or ALT < 3 times the lab's upper normal limit
• Alkaline phosphatase < 3 times the lab's upper normal limit
• No previous systemic chemotherapy
• No previous radiotherapy to the brain
• Written consent

Exclusion Criteria

• Serious medical or neurological condition with a poor prognosis
• HIV infection
• Second cancer requiring radiotherapy or chemotherapy (contact the study coordinat if necessary)
• Hypersensitivity to temozolomide
• Conditions associated with regular vomiting that might affect oral administration of the drugs
• Psychological, familial, social or geographical circumstances with major implications for compliance with the study visit schedule
• Patient was taking part in other intervention studies within a month of starting this study

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Heidelberg University

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr. Wolfgang Wick

Chairman and Director Neurooncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael Weller

Role: STUDY_DIRECTOR

University of Zurich

Wolfgang Wick

Role: PRINCIPAL_INVESTIGATOR

Heidelberg University

Locations

University of Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

University of Frankfurt

Frankfurt am Main, Hesse, Germany

Charite Berlin

Berlin, , Germany

University of Bochum

Bochum, , Germany

University of Bonn

Bonn, , Germany

University of Dresden

Dresden, , Germany

University of Düsseldorf

Düsseldorf, , Germany

University of Erlangen

Erlangen, , Germany

University of Essen

Essen, , Germany

University of Freiburg

Freiburg im Breisgau, , Germany

University of Hamburg

Hamburg, , Germany

University of Hannover II

Hanover, , Germany

University of Hannover

Hanover, , Germany

University of Homburg

Homburg, , Germany

University of Kiel

Kiel, , Germany

University of Leipzig

Leipzig, , Germany

University of Mainz

Mainz, , Germany

University of Heidelberg

Mannheim, , Germany

University of Marburg

Marburg, , Germany

University of Regensburg

Regensburg, , Germany

University of Tübingen

Tübingen, , Germany

University of Ulm

Ulm, , Germany

University of Zurich

Zurich, Canton of Zurich, Switzerland

Countries

Germany; Switzerland

References

Wick A, Kessler T, Platten M, Meisner C, Bamberg M, Herrlinger U, Felsberg J, Weyerbrock A, Papsdorf K, Steinbach JP, Sabel M, Vesper J, Debus J, Meixensberger J, Ketter R, Hertler C, Mayer-Steinacker R, Weisang S, Bolting H, Reuss D, Reifenberger G, Sahm F, von Deimling A, Weller M, Wick W. Superiority of temozolomide over radiotherapy for elderly patients with RTK II methylation class, MGMT promoter methylated malignant astrocytoma. Neuro Oncol. 2020 Aug 17;22(8):1162-1172. doi: 10.1093/neuonc/noaa033.

Reference Type: DERIVED

PMID: 32064499 (View on PubMed)

Wick W, Platten M, Meisner C, Felsberg J, Tabatabai G, Simon M, Nikkhah G, Papsdorf K, Steinbach JP, Sabel M, Combs SE, Vesper J, Braun C, Meixensberger J, Ketter R, Mayer-Steinacker R, Reifenberger G, Weller M; NOA-08 Study Group of Neuro-oncology Working Group (NOA) of German Cancer Society. Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol. 2012 Jul;13(7):707-15. doi: 10.1016/S1470-2045(12)70164-X. Epub 2012 May 10.

Reference Type: DERIVED

PMID: 22578793 (View on PubMed)

Other Identifiers

05-01

Identifier Type: REGISTRY

Identifier Source: secondary_id

NOA-08

Identifier Type: -

Identifier Source: org_study_id