Randomized Phase III Study of Sequential Radiochemotherapy of Anaplastic Glioma With PCV or Temozolomide

NCT ID: NCT00717210

Last Updated: 2008-07-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

318 participants

Study Classification

INTERVENTIONAL

Study Start Date

1999-06-30

Study Completion Date

2008-03-31

Brief Summary

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Background: The optimal treatment of anaplastic gliomas is controversial. Standard of care in most centers is still radiotherapy. This phase III study compared the efficacy and safety of radiotherapy vs chemotherapy in patients (pts) with newly-diagnosed, supratentorial gliomas of WHO grade III.

Methods: Pts were randomized 2:1:1 between June 1999 and February 2005 in 34 German centers to receive (i) a 6-week course of radiotherapy (1,8-2 Gy fractions, total dose 54-60 Gy) or (ii) four 6-week cycles of CCNU at 110 mg mg/m2 on day 1, vincristine at 2 mg on days 8 and 29 and procarbazine at 60 mg/m2 on days 8-21 or eight 4-week cycles of 200 mg/m2 temozolomide on days 1-5. Treatment was stopped prematurely at disease progression or occurrence of unacceptable toxicity. At this time or at disease progression, treatment in the radiotherapy group was continued with one of the chemotherapies (1:1 randomization) and with radiotherapy in both chemotherapy groups. The primary endpoint was time-to-treatment-failure (TTF) defined as progression after radiotherapy and one chemotherapy in either sequence, or any time before if further therapy could not be employed. Assuming a 50% improvement in TTF of starting with chemotherapy, 318 pts were to be enrolled to provide 80% power to achieve statistical significance at a one-sided level of 0.05.

Detailed Description

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Conditions

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Anaplastic Astrocytoma Oligodendroglioma Oligoastrocytoma

Keywords

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1p/19q loss MGMT prognostic factors PCV temozolomide

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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A

Conventional Radiotherapy

Group Type ACTIVE_COMPARATOR

Focal radiotherapy

Intervention Type RADIATION

54-60 Gy in 28-30 fractions over 6-7 weeks

B1/2

1:1 randomization between temozolomide and procarbazine/lomustine/vincristine (PCV)

Group Type EXPERIMENTAL

Temozolomide

Intervention Type DRUG

200 mg/m2 body surface on days 1-5 every 28 days for 8 cycles; and again for another 4 cycles at primary progression

Interventions

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Temozolomide

200 mg/m2 body surface on days 1-5 every 28 days for 8 cycles; and again for another 4 cycles at primary progression

Intervention Type DRUG

Focal radiotherapy

54-60 Gy in 28-30 fractions over 6-7 weeks

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

* written informed consent
* centrally confirmed anaplastic glioma according to the WHO-classification 1998/2000
* age ≥ 18 years
* Karnofsky performance status (KPS) of 70 or higher
* no prior systemic chemotherapy or radiation therapy of the brain
* no HIV infection
* adequate bone marrow reserve, liver function, and renal function
* Patients on corticosteroids had to be on a stable or decreasing dosage within the 14 days prior to randomization

Exclusion Criteria

* Glioblastoma
* infratentorial localization of the tumor
* pregnancy or lactation period
* serious medical or neurological comorbidity
* additional malignancy requiring radio- or chemotherapy
* known hypersensitivity against study drugs
* inability to swallow
* frequent emesis
* psychological. familial, sociological or geographical situations impairing compliance with F/U examinations
* parallel participation in other studies
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital Tuebingen

OTHER

Sponsor Role collaborator

Heinrich-Heine University, Duesseldorf

OTHER

Sponsor Role collaborator

Heidelberg University

OTHER

Sponsor Role collaborator

Charite University, Berlin, Germany

OTHER

Sponsor Role collaborator

University Hospital, Essen

OTHER

Sponsor Role collaborator

University of Leipzig

OTHER

Sponsor Role collaborator

University Hospital, Bonn

OTHER

Sponsor Role collaborator

German Cancer Research Center

OTHER

Sponsor Role collaborator

University of Zurich

OTHER

Sponsor Role collaborator

Neuro-Oncology Working Group of the German Cancer Society

NETWORK

Sponsor Role lead

Responsible Party

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NOA

Principal Investigators

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Michael Weller, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Neurology, University of Zurich, Switzerland

Wolfgang Wick, MD

Role: STUDY_DIRECTOR

Department of Neurooncology, University of Heidelberg

Locations

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University of Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

Site Status

Neurology and Radiotherapy

Tübingen, Baden-Wurttemberg, Germany

Site Status

Klinikum Aschaffenburg

Aschaffenburg, , Germany

Site Status

Nervenklinik

Bamberg, , Germany

Site Status

Charite

Berlin, , Germany

Site Status

Neurosurgery

Düsseldorf, , Germany

Site Status

Radiotherapy

Erlangen, , Germany

Site Status

Neurology

Essen, , Germany

Site Status

Neurosurgery

Frankfurt, , Germany

Site Status

Neurosurgery

Kiel, , Germany

Site Status

Neurosurgery

Mainz, , Germany

Site Status

County District Hospital

Regensburg, , Germany

Site Status

Countries

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Germany

References

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Wick W, Weller M for the Neurooncology Working Group (NOA) of the German Cancer Society Randomized phase -III study of sequential radiochemotherapy of oligoastrocytic tumors of WHO-grade III with PCV or temozolomide: NOA-04. J Clin Oncol 2008;26(15S):2007.

Reference Type RESULT

Wick W, Roth P, Hartmann C, Hau P, Nakamura M, Stockhammer F, Sabel MC, Wick A, Koeppen S, Ketter R, Vajkoczy P, Eyupoglu I, Kalff R, Pietsch T, Happold C, Galldiks N, Schmidt-Graf F, Bamberg M, Reifenberger G, Platten M, von Deimling A, Meisner C, Wiestler B, Weller M; Neurooncology Working Group (NOA) of the German Cancer Society. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro Oncol. 2016 Nov;18(11):1529-1537. doi: 10.1093/neuonc/now133. Epub 2016 Jul 1.

Reference Type DERIVED
PMID: 27370396 (View on PubMed)

Other Identifiers

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NOA-04

Identifier Type: -

Identifier Source: org_study_id