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

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.

Conditions

• Anaplastic Astrocytoma
• Oligodendroglioma
• Oligoastrocytoma

Interventions

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

Sponsors & Collaborators

• University Hospital Tuebingen

  collaborator OTHER

• Heinrich-Heine University, Duesseldorf

  collaborator OTHER

• Heidelberg University

  collaborator OTHER

• Charite University, Berlin, Germany

  collaborator OTHER

• University Hospital, Essen

  collaborator OTHER

• University of Leipzig

  collaborator OTHER

• University Hospital, Bonn

  collaborator OTHER

• German Cancer Research Center

  collaborator OTHER

• University of Zurich

  collaborator OTHER

• Neuro-Oncology Working Group of the German Cancer Society

  lead NETWORK

Principal Investigators

• Michael Weller, MD · Department of Neurology, University of Zurich, Switzerland

• Wolfgang Wick, MD · Department of Neurooncology, University of Heidelberg

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

1999-06-30

Primary Completion

2005-02-28

Completion

2008-03-31

Countries

• Germany

Study Locations