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

Anaplastic Astrocytoma Clinical Trial

— NOA-04  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00717210
• Other study ID #: NOA-04
• Status: Completed
• Phase: Phase 3
• First received: July 15, 2008
• Last updated: July 16, 2008
• Start date: June 1999
• Est. completion date: March 2008

Study information

• Verified date: July 2008
• Source: Neuro-Oncology Working Group of the German Cancer Society
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 318
• Est. completion date: March 2008
• Est. primary completion date: February 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anaplastic Astrocytoma
• Astrocytoma
• Oligoastrocytoma
• Oligodendroglioma

Intervention

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

Locations

Country	Name	City	State
Germany	Klinikum Aschaffenburg	Aschaffenburg
Germany	Nervenklinik	Bamberg
Germany	Charite	Berlin
Germany	Neurosurgery	Düsseldorf
Germany	Radiotherapy	Erlangen
Germany	Neurology	Essen
Germany	Neurosurgery	Frankfurt
Germany	University of Heidelberg	Heidelberg	Baden-Württemberg
Germany	Neurosurgery	Kiel
Germany	Neurosurgery	Mainz
Germany	County District Hospital	Regensburg
Germany	Neurology and Radiotherapy	Tübingen	Baden-Württemberg

Sponsors (10)

Lead Sponsor	Collaborator
Neuro-Oncology Working Group of the German Cancer Society	Charite University, Berlin, Germany, German Cancer Research Center, Heidelberg University, Heinrich-Heine University, Duesseldorf, University Hospital Tuebingen, University Hospital, Bonn, University Hospital, Essen, University of Leipzig, University of Zurich

Country where clinical trial is conducted

Germany, 

References & Publications (1)

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time-to-treatment-failure defined as progression after radiotherapy and one chemotherapy in either sequence		1999-2008	No
Secondary	Progression-free survival Overall Survival Toxicity Response rates		1999-2012	No

External Links

•   Homepage of the NOA