Randomized Phase III Study of Sequential Radiochemotherapy of Anaplastic Glioma With PCV or Temozolomide (NOA-04)

This study has been completed.
Sponsor:
Collaborators:
University Hospital Tuebingen
Heinrich-Heine University, Duesseldorf
Heidelberg University
Charite University, Berlin, Germany
University Hospital, Essen
University of Leipzig
University Hospital, Bonn
German Cancer Research Center
University of Zurich
Information provided by:
Neuro-Oncology Working Group of the German Cancer Society
ClinicalTrials.gov Identifier:
NCT00717210
First received: July 15, 2008
Last updated: July 16, 2008
Last verified: July 2008
  Purpose

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.


Condition Intervention Phase
Anaplastic Astrocytoma
Oligodendroglioma
Oligoastrocytoma
Drug: Temozolomide
Radiation: Focal radiotherapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: NOA-04 Randomized Phase III Study of Sequential Radiochemotherapy of Anaplastic Glioma With PCV or Temozolomide

Resource links provided by NLM:


Further study details as provided by Neuro-Oncology Working Group of the German Cancer Society:

Primary Outcome Measures:
  • Time-to-treatment-failure defined as progression after radiotherapy and one chemotherapy in either sequence [ Time Frame: 1999-2008 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival Overall Survival Toxicity Response rates [ Time Frame: 1999-2012 ] [ Designated as safety issue: No ]

Enrollment: 318
Study Start Date: June 1999
Study Completion Date: March 2008
Primary Completion Date: February 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A
Conventional Radiotherapy
Radiation: Focal radiotherapy
54-60 Gy in 28-30 fractions over 6-7 weeks
Experimental: B1/2
1:1 randomization between temozolomide and procarbazine/lomustine/vincristine (PCV)
Drug: 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00717210

Locations
Germany
University of Heidelberg
Heidelberg, Baden-Württemberg, Germany, 69120
Neurology and Radiotherapy
Tübingen, Baden-Württemberg, Germany, 72076
Klinikum Aschaffenburg
Aschaffenburg, Germany
Nervenklinik
Bamberg, Germany
Charite
Berlin, Germany
Neurosurgery
Düsseldorf, Germany
Radiotherapy
Erlangen, Germany
Neurology
Essen, Germany
Neurosurgery
Frankfurt, Germany
Neurosurgery
Kiel, Germany
Neurosurgery
Mainz, Germany
County District Hospital
Regensburg, Germany
Sponsors and Collaborators
Neuro-Oncology Working Group of the German Cancer Society
University Hospital Tuebingen
Heinrich-Heine University, Duesseldorf
Heidelberg University
Charite University, Berlin, Germany
University Hospital, Essen
University of Leipzig
University Hospital, Bonn
German Cancer Research Center
University of Zurich
Investigators
Principal Investigator: Michael Weller, MD Department of Neurology, University of Zurich, Switzerland
Study Director: Wolfgang Wick, MD Department of Neurooncology, University of Heidelberg
  More Information

Additional Information:
Publications:
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.

Responsible Party: Prof. Dr. Michael Weller, NOA
ClinicalTrials.gov Identifier: NCT00717210     History of Changes
Other Study ID Numbers: NOA-04
Study First Received: July 15, 2008
Last Updated: July 16, 2008
Health Authority: Germany: Ethics Commission

Keywords provided by Neuro-Oncology Working Group of the German Cancer Society:
1p/19q loss
MGMT
prognostic factors
PCV
temozolomide

Additional relevant MeSH terms:
Astrocytoma
Oligodendroglioma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 26, 2014