NCT00717210

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
318

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Jun 1999

Longer than P75 for phase_3

Geographic Reach
1 country

12 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 1999

Completed
5.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2005

Completed
3.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2008

Completed
5 months until next milestone

First Submitted

Initial submission to the registry

July 15, 2008

Completed
2 days until next milestone

First Posted

Study publicly available on registry

July 17, 2008

Completed
Last Updated

July 17, 2008

Status Verified

July 1, 2008

Enrollment Period

5.7 years

First QC Date

July 15, 2008

Last Update Submit

July 16, 2008

Conditions

Anaplastic AstrocytomaOligodendrogliomaOligoastrocytoma

Keywords

1p/19q lossMGMTprognostic factorsPCVtemozolomide

Outcome Measures

Primary Outcomes (1)

  • Time-to-treatment-failure defined as progression after radiotherapy and one chemotherapy in either sequence

    1999-2008

Secondary Outcomes (1)

  • Progression-free survival Overall Survival Toxicity Response rates

    1999-2012

Study Arms (2)

A

ACTIVE COMPARATOR

Conventional Radiotherapy

Radiation: Focal radiotherapy

B1/2

EXPERIMENTAL

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

Drug: Temozolomide

Interventions

TemozolomideDRUG

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

B1/2
Focal radiotherapyRADIATION

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

A

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (12)

University of Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Neurology and Radiotherapy

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Klinikum Aschaffenburg

Aschaffenburg, Germany

Location

Nervenklinik

Bamberg, Germany

Location

Charite

Berlin, Germany

Location

Neurosurgery

Düsseldorf, Germany

Location

Radiotherapy

Erlangen, Germany

Location

Neurology

Essen, Germany

Location

Neurosurgery

Frankfurt, Germany

Location

Neurosurgery

Kiel, Germany

Location

Neurosurgery

Mainz, Germany

Location

County District Hospital

Regensburg, Germany

Location

Related Publications (2)

  • 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.

    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.

    PMID: 27370396DERIVED

MeSH Terms

Conditions

AstrocytomaOligodendroglioma

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

GliomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

DacarbazineTriazenesOrganic ChemicalsImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Michael Weller, MD

    Department of Neurology, University of Zurich, Switzerland

    PRINCIPAL INVESTIGATOR

  • Wolfgang Wick, MD

    Department of Neurooncology, University of Heidelberg

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NETWORK

Study Record Dates

First Submitted

July 15, 2008

First Posted

July 17, 2008

Study Start

June 1, 1999

Primary Completion

February 1, 2005

Study Completion

March 1, 2008

Last Updated

July 17, 2008

Record last verified: 2008-07

Locations

DE(12)