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

NCT01502241 | Completed Phase 3

• 2 other identifiers: NOA-0805-01
• Study Type: interventional
• Target: 412
• Locations: 2 countries
• Sites: 23

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.

Conditions

Glioblastoma; Anaplastic Astrocytoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Overall survival

  The primary endpoint was overall survival, measured in days from surgery to death for any reason. Patients alive at the day of the last contact were censored.

  12 months

Secondary Outcomes (3)

• Event-free survival

  12 months

• Best response

  Within the first 8 months after surgery

• Molecular prognostic or predictive biomarkers

  At 12 months

Study Arms (2)

Radiotherapy

ACTIVE COMPARATOR

6 weeks standard partial brain treatment.

Radiation: Radiotherapy of the partial brain.

Temozolomide

EXPERIMENTAL

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

Drug: Temozolomide

Interventions

Temozolomide DRUG

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

Temozolomide

Radiotherapy of the partial brain. RADIATION

60 Gy in 30 fractions à 2 Gy.

Radiotherapy

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Heidelberg University: lead

Study Sites (23)

University of Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

University of Frankfurt

Frankfurt am Main, Hesse, 60528, Germany

Location

Charite Berlin

Berlin, Germany

Location

University of Bochum

Bochum, Germany

Location

University of Bonn

Bonn, Germany

Location

University of Dresden

Dresden, Germany

Location

University of Düsseldorf

Düsseldorf, Germany

Location

University of Erlangen

Erlangen, Germany

Location

University of Essen

Essen, Germany

Location

University of Freiburg

Freiburg im Breisgau, Germany

Location

University of Hamburg

Hamburg, Germany

Location

University of Hannover II

Hanover, Germany

Location

University of Hannover

Hanover, Germany

Location

University of Homburg

Homburg, Germany

Location

University of Kiel

Kiel, Germany

Location

University of Leipzig

Leipzig, Germany

Location

University of Mainz

Mainz, Germany

Location

University of Heidelberg

Mannheim, Germany

Location

University of Marburg

Marburg, Germany

Location

University of Regensburg

Regensburg, Germany

Location

University of Tübingen

Tübingen, Germany

Location

University of Ulm

Ulm, Germany

Location

University of Zurich

Zurich, Canton of Zurich, 8091, Switzerland

Location

Related Publications (2)

• 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.

  PMID: 32064499 DERIVED

• 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.

  PMID: 22578793 DERIVED

MeSH Terms

Conditions

Glioblastoma; Astrocytoma; Brain Neoplasms

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Michael Weller

  University of Zurich

  STUDY DIRECTOR

• Wolfgang Wick

  Heidelberg University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chairman and Director Neurooncology

Study Record Dates

• First Submitted: December 24, 2011
• First Posted: December 30, 2011
• Study Start: January 1, 2005
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2011
• Last Updated: December 30, 2011

Record last verified: 2011-12

Locations

DE (22); CH (1)