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

    Phase 3
  • Study Type

  • Status

    Completed No Results Posted
  • Intervention/Treatment

    temozolomide ...
  • Study Participants

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.
Study Started
Jun 30
Primary Completion
Feb 28
Study Completion
Mar 31
Last Update
Jul 17

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

Radiation Focal radiotherapy

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

A Active Comparator

Conventional Radiotherapy

B1/2 Experimental

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


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:

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
No Results Posted