Glioblastoma MultiformePhase 3NCT01450449
Short Course vs. Standard Course Radiotherapy in Elderly and/or Frail Patients With Glioblastoma Multiforme
A Phase 3 study testing Radiotherapy in people with Glioblastoma Multiforme, run by International Atomic Energy Agency at 15 sites in 14 countries.
Trial summary
This is a multi-centre prospective, non-inferiority trial. Patients will be randomized to two treatment groups in a 1:1 ratio and will be stratified by age, Karnofsky Performance Status and extent of the surgical resection. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- Radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 115 participants
- Where
- 15 sitesin 14 countries
- Study dates
- Feb 2009to Nov 2014
- 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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histopathologically confirmed newly diagnosed glioblastoma multiforme (GBM, WHO grade IV). The histological diagnosis must have been made locally after biopsy or neurosurgical tumour resection.
- Initial surgery/biopsy at diagnosis performed < 6 weeks (42 days) prior to randomization.
- Patient's age is 50 years or older.
- Karnofsky performance status is 50% or higher.
- Patients may have received and continue to receive corticosteroids, but they have to be on a stable or decreasing dose for at least 14 days prior to randomization.
- Patients must not have received prior chemotherapy or radiotherapy.
Show all 10Show fewer
- Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in either English or any other language the questionnaire is officially translated into. The baseline assessment (prior to start of radiotherapy) must already have been completed. Inability (illiteracy, loss of sight, or other equivalent reason) to complete the questionnaires will not make the patient ineligible for the study. In centres where patients are not able to read or write, proxy interviews will be conducted in-person or via telephone by the nurse at that particular centre.
- Patient consent must be obtained according to local institutional policy. It will be the responsibility of the local participating investigators to obtain the necessary local clearance, and to indicate in writing to the IAEA Study Coordinator that such clearance has been obtained, before the trial can commence in that centre. A copy of the initial full board ERB approval and approved consent form must be sent to the Project Officer at IAEA. The patient must sign the consent form prior to randomization or registration.
- Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
- Protocol treatment is to begin within 2 weeks of patient randomization.
Who cannot join
- Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for 3 or more years.
- Patients with a serious active infection or other serious underlying medical conditions that would impair the ability of the patient to receive protocol treatment or comply with protocol.
Trial locations and contacts
15 sites in 14 countries.
15 sites in 14 countries
Brazil2 sites
Irmandade de Santa Casa de Misericordia de Porto Alegre
Porto Alegre, 90050-70
Hospital "A.C. Camargo", Fundacao "Antonio Prudente"
São Paulo, 01509-010
India1 site
Postgraduate Institute of Medical Education and Research (PGIMER)
Chandigarh, 160 012
Indonesia1 site
Cipto Magunkusumo General Hospital, University of Indonesia
Jakarta, 10430
Thailand1 site
Division of Therapeutic Radiology and Oncology, Faculty of Medicine, Chiang Mai University
Chiang Mai, 50002
Tunisia1 site
Institut National de Cancer Salah Aziz, Ministere de la Sante Publique
Tunis, 1006
About this study
Official title: A Randomized Phase III Study of Short Course (One-week) Radiation Therapy Versus Standard Course (Three-week) Radiation Therapy in Elderly and/or Frail Patients With Newly Diagnosed Glioblastoma Multiforme
This is a multi-centre prospective, non-inferiority trial. Patients will be randomized to two treatment groups in a 1:1 ratio and will be stratified by age, Karnofsky Performance Status and extent of the surgical resection.
This study will assess the effect of a one-week radiotherapy regimen in comparison with a three-week radiotherapy regimen on the survival of elderly and/or frail patients with glioblastoma multiforme (Frail: ≥>50 years old and with a KPS of 50% or less50%-70%; Elderly and frail: ≥65 years and with a KPS of 50% - 70%; Elderly: ≥65 years and with a KPS of 80% - 100%).
Read the detailed description
This is a multi-centre prospective, non-inferiority trial. Patients will be randomized to two treatment groups in a 1:1 ratio and will be stratified by:
- Age (<65 and ≥65 years old)
- Karnofsky Performance Status (≤70 and > 7050 or higher)
- Extent of the resection at surgery (biopsy only versus complete/near total and gross total or incomplete /partial resection)
Randomization:
Patients will be randomized to receive one of the two following treatments:
Arm 1:
- Short Radiotherapy
- 25 Gy/5 fractions
- 1 week (5 fractions per week)
Arm 2:
- Regular Radiotherapy
- 40 Gy/15 fractions
- 3 weeks (5 fractions per week)
- Conditions
- Glioblastoma Multiforme
- Being tested
- Radiotherapy
- Keywords
- GBM, fractionation, short course, standard course
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RadiotherapyRadiation
25 Gy in 5 daily fractions over 1 week
RadiotherapyRadiation
40 Gy in 15 daily fractions over 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 - Short Course Radiotherapy | Experimental | Short Course Receives: Radiation: Radiotherapy |
| Arm 2 - Standard Course Radiotherapy | Active comparator | Standard Course Receives: Radiation: Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
The time from randomization to the time of death from any cause.
Measured: 2.5 years
Secondary outcomes (2)
Progression-free survival
2.5 years including six months of follow-up after initial accrual.
Measured: 2.5 years
Quality of Life
Quality of life will be assessed prior to study randomization and 4 weeks following completion of radiotherapy.
Measured: 2.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2011 (estimated)
- Study startFeb 2009
- Primary completionDec 2013
- Study completionNov 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma MultiformeStudies 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
- 115 participants (actual)
Sponsor and investigators
- Lead sponsor
- International Atomic Energy Agency
- Sponsor type
- Other government
- Collaborators
- Fundación Escuela de Medicina Nuclear, N.N. Alexandrov National Cancer Centre, Hospital A.C. Camargo, Irmandade Santa Casa de Misericórdia de Porto Alegre, Instituto de Radiomedicina (IRAM), Post Graduate Institute of Medical Education and Research, Chandigarh, Dr Cipto Mangunkusumo General Hospital, Maria Sklodowska-Curie National Research Institute of Oncology, Chiang Mai University, Salah Azaïz Cancer Institute, Wilson Roa Professional Corporation, Cancer Trials Ireland, Ege University, High Technology Medical Center
- Responsible party
- Sponsor
- Investigators
- Elena Fidarova, Principal investigator, International Atomic Energy Agency
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01450449
- Sponsor's protocol ID
- E33033
- Status last verified
- Mar 2015
- First submitted
- 10 Oct 2011
- Last updated
- 24 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Newall J, Ransohoff J, Kaplan B. Glioblastoma in the older patient: how long a course of radiotherapy is necessary? J Neurooncol. 1988 Dec;6(4):325-7. doi: 10.1007/BF00177427.
PubMed 2851647Bauman GS, Gaspar LE, Fisher BJ, Halperin EC, Macdonald DR, Cairncross JG. A prospective study of short-course radiotherapy in poor prognosis glioblastoma multiforme. Int J Radiat Oncol Biol Phys. 1994 Jul 1;29(4):835-9. doi: 10.1016/0360-3016(94)90573-8.
PubMed 8040031Kleinberg L, Slick T, Enger C, Grossman S, Brem H, Wharam MD Jr. Short course radiotherapy is an appropriate option for most malignant glioma patients. Int J Radiat Oncol Biol Phys. 1997 Apr 1;38(1):31-6. doi: 10.1016/s0360-3016(97)00222-8.
PubMed 9212001Jeremic B, Shibamoto Y, Grujicic D, Milicic B, Stojanovic M, Nikolic N, Dagovic A, Aleksandrovic J. Short-course radiotherapy in elderly and frail patients with glioblastoma multiforme. A phase II study. J Neurooncol. 1999 Aug;44(1):85-90. doi: 10.1023/a:1006356021734.
PubMed 10582674Roa W, Brasher PM, Bauman G, Anthes M, Bruera E, Chan A, Fisher B, Fulton D, Gulavita S, Hao C, Husain S, Murtha A, Petruk K, Stewart D, Tai P, Urtasun R, Cairncross JG, Forsyth P. Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol. 2004 May 1;22(9):1583-8. doi: 10.1200/JCO.2004.06.082. Epub 2004 Mar 29.
PubMed 15051755Roa W, Kepka L, Kumar N, Sinaika V, Matiello J, Lomidze D, Hentati D, Guedes de Castro D, Dyttus-Cebulok K, Drodge S, Ghosh S, Jeremic B, Rosenblatt E, Fidarova E. International Atomic Energy Agency Randomized Phase III Study of Radiation Therapy in Elderly and/or Frail Patients With Newly Diagnosed Glioblastoma Multiforme. J Clin Oncol. 2015 Dec 10;33(35):4145-50. doi: 10.1200/JCO.2015.62.6606. Epub 2015 Sep 21.
PubMed 26392096
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase III Study of Short Course (One-week) Radiation Therapy Versus Standard Course (Three-week) Radiation Therapy in Elderly and/or Frail Patients With Newly Diagnosed Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT01450449
- Acronym / sponsor ID
- E33033
- Conditions
- Glioblastoma Multiforme
- Keywords
- GBM, fractionation, short course, standard course
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 115 participants (actual)
- Lead sponsor
- International Atomic Energy AgencyOther government
- Collaborators
- Fundación Escuela de Medicina Nuclear, N.N. Alexandrov National Cancer Centre, Hospital A.C. Camargo, Irmandade Santa Casa de Misericórdia de Porto Alegre, Instituto de Radiomedicina (IRAM), Post Graduate Institute of Medical Education and Research, Chandigarh, Dr Cipto Mangunkusumo General Hospital, Maria Sklodowska-Curie National Research Institute of Oncology, Chiang Mai University, Salah Azaïz Cancer Institute, Wilson Roa Professional Corporation, Cancer Trials Ireland, Ege University, High Technology Medical Center
- Study start
- Feb 2009
- Primary completion
- Dec 2013 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 12 Oct 2011 (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.
This is a multi-centre prospective, non-inferiority trial. Patients will be randomized to two treatment groups in a 1:1 ratio and will be stratified by age, Karnofsky Performance Status and extent of the surgical resection.
This study will assess the effect of a one-week radiotherapy regimen in comparison with a three-week radiotherapy regimen on the survival of elderly and/or frail patients with glioblastoma multiforme (Frail: ≥>50 years old and with a KPS of 50% or less50%-70%; Elderly and frail: ≥65 years and with a KPS of 50% - 70%; Elderly: ≥65 years and with a KPS of 80% - 100%).
Detailed description
This is a multi-centre prospective, non-inferiority trial. Patients will be randomized to two treatment groups in a 1:1 ratio and will be stratified by:
- Age (<65 and ≥65 years old)
- Karnofsky Performance Status (≤70 and > 7050 or higher)
- Extent of the resection at surgery (biopsy only versus complete/near total and gross total or incomplete /partial resection)
Randomization:
Patients will be randomized to receive one of the two following treatments:
Arm 1:
- Short Radiotherapy
- 25 Gy/5 fractions
- 1 week (5 fractions per week)
Arm 2:
- Regular Radiotherapy
- 40 Gy/15 fractions
- 3 weeks (5 fractions per week)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 - Short Course Radiotherapy | Experimental | Radiation: RadiotherapyShort Course |
| Arm 2 - Standard Course Radiotherapy | Active comparator | Radiation: RadiotherapyStandard Course |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Histopathologically confirmed newly diagnosed glioblastoma multiforme (GBM, WHO grade IV). The histological diagnosis must have been made locally after biopsy or neurosurgical tumour resection.
- Initial surgery/biopsy at diagnosis performed < 6 weeks (42 days) prior to randomization.
- Patient's age is 50 years or older.
- Karnofsky performance status is 50% or higher.
- Patients may have received and continue to receive corticosteroids, but they have to be on a stable or decreasing dose for at least 14 days prior to randomization.
Key exclusion criteria (2 listed)
- Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for 3 or more years.
- Patients with a serious active infection or other serious underlying medical conditions that would impair the ability of the patient to receive protocol treatment or comply with protocol.
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 |
|---|---|---|
| Radiotherapy25 Gy in 5 daily fractions over 1 week | Radiation | Arm 1 - Short Course Radiotherapy |
| Radiotherapy40 Gy in 15 daily fractions over 3 weeks | Radiation | Arm 2 - Standard Course Radiotherapy |
Primary outcome
Overall Survival
Time frame: 2.5 years
The time from randomization to the time of death from any cause.
2 secondary outcomes
Progression-free survival
Time frame: 2.5 years
Quality of Life
Time frame: 2.5 years
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 24 Mar 2015.
- Background: PubMed 2851647Newall J, Ransohoff J, Kaplan B. Glioblastoma in the older patient: how long a course of radiotherapy is necessary? J Neurooncol. 1988 Dec;6(4):325-7. doi: 10.1007/BF00177427.
- Background: PubMed 8040031Bauman GS, Gaspar LE, Fisher BJ, Halperin EC, Macdonald DR, Cairncross JG. A prospective study of short-course radiotherapy in poor prognosis glioblastoma multiforme. Int J Radiat Oncol Biol Phys. 1994 Jul 1;29(4):835-9. doi: 10.1016/0360-3016(94)90573-8.
- Background: PubMed 9212001Kleinberg L, Slick T, Enger C, Grossman S, Brem H, Wharam MD Jr. Short course radiotherapy is an appropriate option for most malignant glioma patients. Int J Radiat Oncol Biol Phys. 1997 Apr 1;38(1):31-6. doi: 10.1016/s0360-3016(97)00222-8.
- Background: PubMed 10582674Jeremic B, Shibamoto Y, Grujicic D, Milicic B, Stojanovic M, Nikolic N, Dagovic A, Aleksandrovic J. Short-course radiotherapy in elderly and frail patients with glioblastoma multiforme. A phase II study. J Neurooncol. 1999 Aug;44(1):85-90. doi: 10.1023/a:1006356021734.
- Background: PubMed 15051755Roa W, Brasher PM, Bauman G, Anthes M, Bruera E, Chan A, Fisher B, Fulton D, Gulavita S, Hao C, Husain S, Murtha A, Petruk K, Stewart D, Tai P, Urtasun R, Cairncross JG, Forsyth P. Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol. 2004 May 1;22(9):1583-8. doi: 10.1200/JCO.2004.06.082. Epub 2004 Mar 29.
- Derived from this study: PubMed 26392096Roa W, Kepka L, Kumar N, Sinaika V, Matiello J, Lomidze D, Hentati D, Guedes de Castro D, Dyttus-Cebulok K, Drodge S, Ghosh S, Jeremic B, Rosenblatt E, Fidarova E. International Atomic Energy Agency Randomized Phase III Study of Radiation Therapy in Elderly and/or Frail Patients With Newly Diagnosed Glioblastoma Multiforme. J Clin Oncol. 2015 Dec 10;33(35):4145-50. doi: 10.1200/JCO.2015.62.6606. Epub 2015 Sep 21.
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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.
Elena Fidarova principal investigator
International Atomic Energy Agency
15 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Radiotherapy in people with Glioblastoma Multiforme, run by International Atomic Energy Agency at 15 sites in 14 countries.
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 10 inclusion and 2 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 24 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Brazil, Argentina, Belarus, Canada, Chile and 9 more countries. 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?
Overall Survival (time frame: 2.5 years). 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 NCT01450449, which also lists 6 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 24 Mar 2015.