NCT00717210: NOA-04

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

Completed Phase 3 Last updated 16 July 2008

What this trial tests

Phase 3 trial testing Temozolomide in Anaplastic Astrocytoma in 318 participants. Completed in 1 March 2008.

Timeline

1 June 1999

Primary endpoint
1 February 2005

1 March 2008

Quick facts

Lead sponsor	Neuro-Oncology Working Group of the German Cancer Society
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	318
Start date	1 June 1999
Primary completion	1 February 2005
Estimated completion	1 March 2008
Sites	12 locations across Germany

Drugs / interventions tested

• Temozolomide (temozolomide) — full drug profile →
• Focal radiotherapy

Conditions studied

• Anaplastic Astrocytoma — all drugs for Anaplastic Astrocytoma →
• Oligodendroglioma — all drugs for Oligodendroglioma →
• Oligoastrocytoma — all drugs for Oligoastrocytoma →

Sponsor

Neuro-Oncology Working Group of the German Cancer Society

Who can join

18 and older, any sex, with Anaplastic Astrocytoma or Oligodendroglioma. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Time-to-treatment-failure defined as progression after radiotherapy and one chemotherapy in either sequence
  Time frame: 1999-2008

Sponsor's own description

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.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide.
   Wick W, Roth P, Hartmann C, Hau P, et al · · 2016 · cited 161× · PMID 27370396 · DOI 10.1093/neuonc/now133
2. Assessing CpG island methylator phenotype, 1p/19q codeletion, and MGMT promoter methylation from epigenome-wide data in the biomarker cohort of the NOA-04 trial.
   Wiestler B, Capper D, Hovestadt V, Sill M, et al · · 2014 · cited 72× · PMID 25028501 · DOI 10.1093/neuonc/nou138
3. Clinical Neuropathology practice news 2-2014: ATRX, a new candidate biomarker in gliomas.
   Haberler C, Wöhrer A. · · 2014 · cited 14× · PMID 24559763 · DOI 10.5414/np300758
4. Recent Advancements and Future Perspectives on Molecular Biomarkers in Adult Lower-Grade Gliomas.
   Fleming JL, Chakravarti A. · · 2025 · PMID 39841423 · DOI 10.1097/ppo.0000000000000758