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

Study Overview
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Brief Summary
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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.

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

Conditions
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Anaplastic Astrocytoma, Oligodendroglioma, Oligoastrocytoma

Intervention / Treatment
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* Drug: Temozolomide
* Radiation: Focal radiotherapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Conventional Radiotherapy | Radiation: Focal radiotherapy<br>* 54-60 Gy in 28-30 fractions over 6-7 weeks<br>|
| Experimental: B1/2<br>1:1 randomization between temozolomide and procarbazine/lomustine/vincristine (PCV) | Drug: Temozolomide<br>* 200 mg/m2 body surface on days 1-5 every 28 days for 8 cycles; and again for another 4 cycles at primary progression<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-to-treatment-failure defined as progression after radiotherapy and one chemotherapy in either sequence |  | 1999-2008 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival Overall Survival Toxicity Response rates |  | 1999-2012 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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1p/19q loss, MGMT, prognostic factors, PCV, temozolomide