Short Course vs. Standard Course Radiotherapy in Elderly and/or Frail Patients With Glioblastoma Multiforme

• Progression-free survival [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
  2.5 years including six months of follow-up after initial accrual.
• Quality of Life [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
  Quality of life will be assessed prior to study randomization and 4 weeks following completion of radiotherapy.

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%).

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)

• Radiation: Radiotherapy
  25 Gy in 5 daily fractions over 1 week
• Radiation: Radiotherapy
  40 Gy in 15 daily fractions over 3 weeks

• Experimental: Arm 1 - Short Course Radiotherapy
  Short Course
  Intervention: Radiation: Radiotherapy
• Active Comparator: Arm 2 - Standard Course Radiotherapy
  Standard Course
  Intervention: Radiation: Radiotherapy

• 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.
• 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.
• 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.
• 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.
• 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. Epub 2004 Mar 29.

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.

• Fundación Escuela de Medicina Nuclear
• N.N. Alexandrov National Cancer Centre of Belarus
• Hospital A.C. Camargo
• Irmandade Santa Casa de Misericórdia de Porto Alegre
• Instituto de Radiomedicina (IRAM)
• Postgraduate Institute of Medical Education and Research
• Cipto Mangunkusumo General Hospital
• Maria Sklodowska-Curie Memorial Cancer Center, Institute of Oncology
• Chiang Mai University
• Institut National de Cancer Salah Azaiz
• Wilson Roa Professional Corporation
• ICORG- All Ireland Cooperative Oncology Research Group
• Ege University
• High Technology Medical Center