Anaplastic AstrocytomaPhase 3NOA-04NCT00717210
Randomized Phase III Study of Sequential Radiochemotherapy of Anaplastic Glioma With PCV or Temozolomide
A Phase 3 study testing Temozolomide and Focal radiotherapy in people with Anaplastic Astrocytoma and Oligodendroglioma, run by Neuro-Oncology Working Group of the German Cancer Society at 12 sites in Germany.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anaplastic Astrocytoma, Oligodendroglioma, Oligoastrocytoma
- What is being tested?
- Temozolomide and Focal radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 318 participants
- Where
- 12 sitesGermany
- Study dates
- Jun 1999to Mar 2008
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- inability to swallow
- frequent emesis
- psychological. familial, sociological or geographical situations impairing compliance with F/U examinations
- parallel participation in other studies
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
Germany12 sites
Klinikum Aschaffenburg
Aschaffenburg
Nervenklinik
Bamberg
Charite
Berlin
Neurosurgery
Düsseldorf
Radiotherapy
Erlangen
Neurology
Essen
Neurosurgery
Frankfurt
University of Heidelberg
Heidelberg, Baden-Wurttemberg, 69120
Neurosurgery
Kiel
Neurosurgery
Mainz
County District Hospital
Regensburg
Neurology and Radiotherapy
Tübingen, Baden-Wurttemberg, 72076
About this study
Official title: NOA-04 Randomized Phase III Study of Sequential Radiochemotherapy of Anaplastic Glioma With PCV or Temozolomide
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
- Being tested
- Temozolomide, Focal radiotherapy
- Keywords
- 1p/19q loss, MGMT, prognostic factors, PCV, temozolomide
- Medical subject headings
- Astrocytoma, Oligodendroglioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TemozolomideDrug
200 mg/m2 body surface on days 1-5 every 28 days for 8 cycles; and again for another 4 cycles at primary progression
Focal radiotherapyRadiation
54-60 Gy in 28-30 fractions over 6-7 weeks
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | Conventional Radiotherapy Receives: Radiation: Focal radiotherapy |
| B1/2 | Experimental | 1:1 randomization between temozolomide and procarbazine/lomustine/vincristine (PCV) Receives: Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time-to-treatment-failure defined as progression after radiotherapy and one chemotherapy in either sequence
Measured: 1999-2008
Secondary outcomes (1)
Progression-free survival Overall Survival Toxicity Response rates
Measured: 1999-2012
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2008 (estimated)
- Study startJun 1999
- Primary completionFeb 2005
- Study completionMar 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Anaplastic AstrocytomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 318 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neuro-Oncology Working Group of the German Cancer Society
- Sponsor type
- Research network
- Collaborators
- University Hospital Tuebingen, Heinrich-Heine University, Duesseldorf, Heidelberg University, Charite University, Berlin, Germany, University Hospital, Essen, University of Leipzig, University Hospital, Bonn, German Cancer Research Center, University of Zurich
- Investigators
- Michael Weller, MD, Principal investigator, Department of Neurology, University of Zurich, SwitzerlandWolfgang Wick, MD, Study director, Department of Neurooncology, University of Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00717210
- Sponsor's protocol ID
- NOA-04
- Acronym
- NOA-04
- Status last verified
- Jul 2008
- First submitted
- 15 Jul 2008
- Last updated
- 17 Jul 2008
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
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.
PubMed 27370396
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NOA-04 Randomized Phase III Study of Sequential Radiochemotherapy of Anaplastic Glioma With PCV or Temozolomide
- ClinicalTrials.gov ID
- NCT00717210
- Acronym / sponsor ID
- NOA-04 / NOA-04
- Conditions
- Anaplastic Astrocytoma, Oligodendroglioma, Oligoastrocytoma
- Keywords
- 1p/19q loss, MGMT, prognostic factors, PCV, temozolomide
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 318 participants (actual)
- Lead sponsor
- Neuro-Oncology Working Group of the German Cancer SocietyResearch network
- Collaborators
- University Hospital Tuebingen, Heinrich-Heine University, Duesseldorf, Heidelberg University, Charite University, Berlin, Germany, University Hospital, Essen, University of Leipzig, University Hospital, Bonn, German Cancer Research Center, University of Zurich
- Study start
- Jun 1999
- Primary completion
- Feb 2005 (actual)
- Study completion
- Mar 2008 (actual)
- First posted
- 17 Jul 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Radiation: Focal radiotherapyConventional Radiotherapy |
| B1/2 | Experimental | Drug: Temozolomide1:1 randomization between temozolomide and procarbazine/lomustine/vincristine (PCV) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (10 listed)
- Glioblastoma
- infratentorial localization of the tumor
- pregnancy or lactation period
- serious medical or neurological comorbidity
- additional malignancy requiring radio- or chemotherapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Temozolomide200 mg/m2 body surface on days 1-5 every 28 days for 8 cycles; and again for another 4 cycles at primary progression | Drug | B1/2 |
| Focal radiotherapy54-60 Gy in 28-30 fractions over 6-7 weeks | Radiation | A |
Primary outcome
Time-to-treatment-failure defined as progression after radiotherapy and one chemotherapy in either sequence
Time frame: 1999-2008
1 secondary outcome
Progression-free survival Overall Survival Toxicity Response rates
Time frame: 1999-2012
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2008.
- Results publicationWick 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.
- Derived from this study: PubMed 27370396Wick 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.
- Homepage of the NOALink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Weller, MD principal investigator
Department of Neurology, University of Zurich, Switzerland
Wolfgang Wick, MD study director
Department of Neurooncology, University of Heidelberg
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Temozolomide and Focal radiotherapy in people with Anaplastic Astrocytoma and Oligodendroglioma, run by Neuro-Oncology Working Group of the German Cancer Society at 12 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jul 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time-to-treatment-failure defined as progression after radiotherapy and one chemotherapy in either sequence (time frame: 1999-2008). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00717210, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2008.