Clinical trial NCT01450449: Short Course vs. Standard Course Radiotherapy in Elderly and/or Frail Patients With Glioblastoma Multiforme
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Glioblastoma Multiforme
Keywords: GBM, fractionation, short course, standard course
Lead sponsor: International Atomic Energy Agency
Sponsor class: OTHER_GOV
Collaborators: name: Fundación Escuela de Medicina Nuclear
name: N.N. Alexandrov National Cancer Centre of Belarus
name: Hospital A.C. Camargo
name: Irmandade Santa Casa de Misericórdia de Porto Alegre
name: Instituto de Radiomedicina (IRAM)
name: Post Graduate Institute of Medical Education and Research, Chandigarh
name: Dr Cipto Mangunkusumo General Hospital
name: Maria Sklodowska-Curie National Research Institute of Oncology
name: Chiang Mai University
name: Salah Azaïz Cancer Institute
name: Wilson Roa Professional Corporation
name: Cancer Trials Ireland
name: Ege University
name: High Technology Medical Center
First posted: 2011-10-12
Enrollment: 115
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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)

Eligibility criteria: Inclusion Criteria:

* 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.
* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Overall Survival
timeFrame: 2.5 years
Secondary outcomes:
measure: Progression-free survival
timeFrame: 2.5 years
measure: Quality of Life
timeFrame: 2.5 years
Other outcomes:
Locations:
city: Mendoza
country: Argentina
facility: Fundacion Escuela de Medicina Nuclear
city: Minsk
country: Belarus
facility: N.N. Alexandrov National Cancer Centre of Belarus
city: Porto Alegre
country: Brazil
facility: Irmandade de Santa Casa de Misericordia de Porto Alegre
city: Sao Paulo
country: Brazil
facility: Hospital "A.C. Camargo", Fundacao "Antonio Prudente"
city: Edmonton
country: Canada
facility: Wilson Roa Professional Corporation
city: Santiago
country: Chile
facility: Instituto de Radiomedicina (IRAM)
city: Tallinn
country: Estonia
facility: Regionaalhailga
city: Tbilisi
country: Georgia
facility: High Technology Medical Center, University Clinic
city: Chandigarh
country: India
facility: Postgraduate Institute of Medical Education and Research (PGIMER)
city: Jakarta
country: Indonesia
facility: Cipto Magunkusumo General Hospital, University of Indonesia
city: Dublin
country: Ireland
facility: ICORG The All Ireland Cooperative Oncology
city: Warsaw
country: Poland
facility: Marie Curie- Sklodowska Institute of Oncology
city: Chiang Mai
country: Thailand
facility: Division of Therapeutic Radiology and Oncology, Faculty of Medicine, Chiang Mai University
city: Tunis
country: Tunisia
facility: Institut National de Cancer Salah Aziz, Ministere de la Sante Publique
city: Izmir
country: Turkey
facility: Ege University Hospital
Study officials:
affiliation: International Atomic Energy Agency
name: Elena Fidarova
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Bauman 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.
citation: Kleinberg 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.
citation: Jeremic 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.
citation: Roa 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.
citation: Roa 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.