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

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%).

Study Overview

• Status: Completed
• Conditions: Glioblastoma Multiforme
• Intervention / Treatment: Radiation: Radiotherapy; Radiation: Radiotherapy

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 Type: Interventional
• Enrollment (Actual): 115
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Mendoza, Argentina, 5500
    • Fundacion Escuela de Medicina Nuclear
• Belarus
  • Minsk, Belarus, 223040
    • N.N. Alexandrov National Cancer Centre of Belarus
• Brazil
  • Porto Alegre, Brazil, 90050-70
    • Irmandade de Santa Casa de Misericordia de Porto Alegre
  • Sao Paulo, Brazil, 01509-010
    • Hospital "A.C. Camargo", Fundacao "Antonio Prudente"
• Canada
  • Edmonton, Canada, Alberta T6R 2A9
    • Wilson Roa Professional Corporation
• Chile
  • Santiago, Chile, 6671407
    • Instituto de Radiomedicina (IRAM)
• Estonia
  • Tallinn, Estonia
    • Regionaalhailga
• Georgia
  • Tbilisi, Georgia, 0144
    • High Technology Medical Center, University Clinic
• India
  • Chandigarh, India, 160 012
    • Postgraduate Institute of Medical Education and Research (PGIMER)
• Indonesia
  • Jakarta, Indonesia, 10430
    • Cipto Magunkusumo General Hospital, University of Indonesia
• Ireland
  • Dublin, Ireland, 2
    • ICORG The All Ireland Cooperative Oncology
• Poland
  • Warsaw, Poland, 02-781
    • Marie Curie- Sklodowska Institute of Oncology
• Thailand
  • Chiang Mai, Thailand, 50002
    • Division of Therapeutic Radiology and Oncology, Faculty of Medicine, Chiang Mai University
• Tunisia
  • Tunis, Tunisia, 1006
    • Institut National de Cancer Salah Aziz, Ministere de la Sante Publique
• Turkey
  • Izmir, Turkey
    • Ege University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 - Short Course Radiotherapy; Short Course	Radiation: Radiotherapy; 25 Gy in 5 daily fractions over 1 week; Radiation: Radiotherapy; 40 Gy in 15 daily fractions over 3 weeks
Active Comparator: Arm 2 - Standard Course Radiotherapy; Standard Course	Radiation: Radiotherapy; 25 Gy in 5 daily fractions over 1 week; Radiation: Radiotherapy; 40 Gy in 15 daily fractions over 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	The time from randomization to the time of death from any cause.	2.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	2.5 years including six months of follow-up after initial accrual.	2.5 years
Quality of Life	Quality of life will be assessed prior to study randomization and 4 weeks following completion of radiotherapy.	2.5 years

Collaborators and Investigators

• Sponsor: International Atomic Energy Agency
• Collaborators: Postgraduate Institute of Medical Education and Research; Ege University; Dr Cipto Mangunkusumo General Hospital; Chiang Mai University; Irmandade Santa Casa de Misericórdia de Porto Alegre; Maria Sklodowska-Curie National Research Institute of Oncology; Cancer Trials Ireland; Fundación Escuela de Medicina Nuclear; N.N. Alexandrov National Cancer Centre of Belarus; Hospital A.C. Camargo; Instituto de Radiomedicina (IRAM); Salah Azaïz Cancer Institute; Wilson Roa Professional Corporation; High Technology Medical Center
• Investigators: Principal Investigator: Elena Fidarova, International Atomic Energy Agency

Publications and helpful links

General 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: October 10, 2011
• First Submitted That Met QC Criteria: October 10, 2011
• First Posted (Estimate): October 12, 2011

Study Record Updates

• Last Update Posted (Estimate): March 24, 2015
• Last Update Submitted That Met QC Criteria: March 23, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: GBM, fractionation, short course, standard course
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: E33033