Clinical trial NCT00717210: Randomized Phase III Study of Sequential Radiochemotherapy of Anaplastic Glioma With PCV or Temozolomide
Official title: NOA-04 Randomized Phase III Study of Sequential Radiochemotherapy of Anaplastic Glioma With PCV or Temozolomide
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anaplastic Astrocytoma
Oligodendroglioma
Oligoastrocytoma
Keywords: 1p/19q loss
MGMT
prognostic factors
PCV
temozolomide
Lead sponsor: Neuro-Oncology Working Group of the German Cancer Society
Sponsor class: NETWORK
Collaborators: name: University Hospital Tuebingen
name: Heinrich-Heine University, Duesseldorf
name: Heidelberg University
name: Charite University, Berlin, Germany
name: University Hospital, Essen
name: University of Leipzig
name: University Hospital, Bonn
name: German Cancer Research Center
name: University of Zurich
First posted: 2008-07-17
Enrollment: 318
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility 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

Primary outcomes:
measure: Time-to-treatment-failure defined as progression after radiotherapy and one chemotherapy in either sequence
timeFrame: 1999-2008
Secondary outcomes:
measure: Progression-free survival Overall Survival Toxicity Response rates
timeFrame: 1999-2012
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: University of Heidelberg
state: Baden-Württemberg
city: Tübingen
country: Germany
facility: Neurology and Radiotherapy
state: Baden-Württemberg
city: Aschaffenburg
country: Germany
facility: Klinikum Aschaffenburg
city: Bamberg
country: Germany
facility: Nervenklinik
city: Berlin
country: Germany
facility: Charite
city: Düsseldorf
country: Germany
facility: Neurosurgery
city: Erlangen
country: Germany
facility: Radiotherapy
city: Essen
country: Germany
facility: Neurology
city: Frankfurt
country: Germany
facility: Neurosurgery
city: Kiel
country: Germany
facility: Neurosurgery
city: Mainz
country: Germany
facility: Neurosurgery
city: Regensburg
country: Germany
facility: County District Hospital
Study officials:
affiliation: Department of Neurology, University of Zurich, Switzerland
name: Michael Weller, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Neurooncology, University of Heidelberg
name: Wolfgang Wick, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Wick W, Roth P, Hartmann C, Hau P, Nakamura M, Stockhammer F, Sabel MC, Wick A, Koeppen S, Ketter R, Vajkoczy P, Eyupoglu I, Kalff R, Pietsch T, Happold C, Galldiks N, Schmidt-Graf F, Bamberg M, Reifenberger G, Platten M, von Deimling A, Meisner C, Wiestler B, Weller M; Neurooncology Working Group (NOA) of the German Cancer Society. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro Oncol. 2016 Nov;18(11):1529-1537. doi: 10.1093/neuonc/now133. Epub 2016 Jul 1.