Radiation Therapy or Temozolomide in Treating Patients With Gliomas

• ClinicalTrials.gov Identifier: NCT00182819
• Recruitment Status: Completed
• First Posted: September 16, 2005
• Last Update Posted: October 12, 2016
• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Collaborators: NCIC Clinical Trials Group; British Medical Research Council; Trans Tasman Radiation Oncology Group
• Information provided by (Responsible Party): European Organisation for Research and Treatment of Cancer - EORTC

Tracking Information

• First Submitted Date: September 15, 2005
• First Posted Date: September 16, 2005
• Last Update Posted Date: October 12, 2016
• Study Start Date: July 2005
• Actual Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 6, 2012): Progression-free survival [ Time Frame: 5 years ]
• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: February 6, 2012)

• Overall survival [ Time Frame: 5 years ]
• Quality of life as measured by QLQ-C30 v3.0 and EORTC BN-20 [ Time Frame: every 3 months until progression, and then every 6 months until death ]
• Mini-Mental State Examination [ Time Frame: every 3 months until progression, and then every 6 months until death ]
• Adverse events as measured by CTCAE v3.0 [ Time Frame: As indicated in the protocol ]

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Radiation Therapy or Temozolomide in Treating Patients With Gliomas
• Official Title: Primary Chemotherapy With Temozolomide Versus Radiotherapy in Patients With Low Grade Gliomas After Stratification for Genetic 1p Loss: A Phase III Study

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether radiation therapy is more effective than temozolomide in treating gliomas.

PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared to temozolomide in treating patients with gliomas.

Detailed Description

OBJECTIVES:

Primary

• Compare the progression-free survival of patients with low-grade gliomas treated with radiotherapy vs temozolomide.

Secondary

• Compare the overall survival of patients treated with these regimens.
• Determine whether the incidence of late toxicity can be decreased in patients who are randomized to receive temozolomide.
• Compare the toxic effects of these regimens in these patients.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to participating center, chromosome 1p status (deleted vs normal vs undeterminable), contrast enhancement on MRI (yes vs no), age (< 40 years vs ≥ 40 years), and WHO performance status (0 or 1 vs 2). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo radiotherapy once daily, 5 days a week, for a total of 28 fractions (i.e., 5½ weeks).
• Arm II: Patients receive oral temozolomide once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and then every 3 months until disease progression.

After completion of study treatment, patients are followed every 6 months for survival.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A minimum of 699 patients (a total of 466 randomized [233 per treatment arm]) will be accrued for this study within 5 years.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Brain and Central Nervous System Tumors

Intervention

• Drug: temozolomide
  Temozolomide 75 mg/m2 daily x 21 days, q 28 days until progression or for max. 12 cycles
• Radiation: radiation therapy
  50.4 Gy, standard fractionation (28 x 1.8 Gy), conformal techniques

Study Arms

• radiotherapy
  Radiotherapy (control arm), 50.4 Gy, standard fractionation (28 x 1.8 Gy), conformal techniques
  Intervention: Radiation: radiation therapy
• Experimental: Temozolomide
  Temozolomide 75 mg/m2 daily x 21 days, q 28 days until progression or for max. 12 cycles (experimental arm)
  Intervention: Drug: temozolomide

Publications *

• Musat E, Roelofs E, Bar-Deroma R, Fenton P, Gulyban A, Collette L, Stupp R, Weber DC, Bernard Davis J, Aird E, Baumert BG. Dummy run and conformity indices in the ongoing EORTC low-grade glioma trial 22033-26033: First evaluation of quality of radiotherapy planning. Radiother Oncol. 2010 May;95(2):218-24. doi: 10.1016/j.radonc.2010.03.005. Epub 2010 Apr 6.
• Fairchild A, Weber DC, Bar-Deroma R, Gulyban A, Fenton PA, Stupp R, Baumert BG. Quality assurance in the EORTC 22033-26033/CE5 phase III randomized trial for low grade glioma: the digital individual case review. Radiother Oncol. 2012 Jun;103(3):287-92. doi: 10.1016/j.radonc.2012.04.002. Epub 2012 May 3.
• Gao Y, Weenink B, van den Bent MJ, Erdem-Eraslan L, Kros JM, Sillevis Smitt P, Hoang-Xuan K, Brandes AA, Vos M, Dhermain F, Enting R, Ryan GF, Chinot O, Ben Hassel M, van Linde ME, Mason WP, Gijtenbeek JMM, Balana C, von Deimling A, Gorlia T, Stupp R, Hegi ME, Baumert BG, French PJ. Expression-based intrinsic glioma subtypes are prognostic in low-grade gliomas of the EORTC22033-26033 clinical trial. Eur J Cancer. 2018 May;94:168-178. doi: 10.1016/j.ejca.2018.02.023. Epub 2018 Mar 20.
• Baumert BG, Hegi ME, van den Bent MJ, von Deimling A, Gorlia T, Hoang-Xuan K, Brandes AA, Kantor G, Taphoorn MJB, Hassel MB, Hartmann C, Ryan G, Capper D, Kros JM, Kurscheid S, Wick W, Enting R, Reni M, Thiessen B, Dhermain F, Bromberg JE, Feuvret L, Reijneveld JC, Chinot O, Gijtenbeek JMM, Rossiter JP, Dif N, Balana C, Bravo-Marques J, Clement PM, Marosi C, Tzuk-Shina T, Nordal RA, Rees J, Lacombe D, Mason WP, Stupp R. Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study. Lancet Oncol. 2016 Nov;17(11):1521-1532. doi: 10.1016/S1470-2045(16)30313-8. Epub 2016 Sep 27.
• Reijneveld JC, Taphoorn MJB, Coens C, Bromberg JEC, Mason WP, Hoang-Xuan K, Ryan G, Hassel MB, Enting RH, Brandes AA, Wick A, Chinot O, Reni M, Kantor G, Thiessen B, Klein M, Verger E, Borchers C, Hau P, Back M, Smits A, Golfinopoulos V, Gorlia T, Bottomley A, Stupp R, Baumert BG. Health-related quality of life in patients with high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study. Lancet Oncol. 2016 Nov;17(11):1533-1542. doi: 10.1016/S1470-2045(16)30305-9. Epub 2016 Sep 27.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 6, 2012): 709
• Original Enrollment: Not Provided
• Actual Study Completion Date: May 2014
• Actual Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed low-grade glioma, including any of the following types:

  • Astrocytoma (gemistocytic, fibrillary, or protoplasmatic)
  • Oligoastrocytoma
  • Oligodendroglioma
• WHO grade II disease
• Supratentorial tumor location only
• RTOG neurological function 0-3
• Not a candidate for surgical treatment alone

• Requires treatment, as determined by ≥ 1 of the following criteria:

  • Age ≥ 40 years
  • Radiologically-proven progressive lesion
  • New or worsening neurological symptoms other than seizures only (e.g., focal deficits, signs of increased intracranial pressure, or mental deficits)

  • Intractable seizures, defined by both of the following criteria:

    • Experiences persistent seizures that interfere with everyday life activities except driving a car
    • Failed 3 anti-epileptic drug regimens, including ≥ 1 combination regimen
• Tumor material (paraffin-embedded) or histopathologic slides available

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• No chronic hepatitis B or C infection
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST or ALT ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 6 months after completion of study treatment
• No known HIV positivity
• No other serious medical condition
• No other prior or concurrent malignancy except surgically cured carcinoma in situ of the cervix or nonmelanoma skin cancer
• No psychological, familial, sociological, or geographical condition that would preclude study participation
• No medical condition that would preclude receiving oral medication (e.g., frequent vomiting or partial bowel obstruction)

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent growth factors for elevating absolute neutrophil counts for the purpose of temozolomide administration
• No concurrent epoetin alfa
• No concurrent immunotherapy or biologic therapy

Chemotherapy

• No prior chemotherapy
• No other concurrent chemotherapy, including adjuvant chemotherapy for patients randomized to undergo radiotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy to the brain
• No concurrent integrated boost with intensity-modulated radiotherapy

Surgery

• Recovered from prior surgery
• No concurrent surgical tumor debulking

Other

• No prior randomization to this study
• No other concurrent investigational drugs

• No concurrent regular use of agents known to be radiosensitizers or radioprotectors (e.g., cyclooxygenase-2 inhibitors, thalidomide, or amifostine) during study radiotherapy

  • Occasional use of nonsteroidal anti-inflammatory drugs for pain allowed

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Canada, Egypt, France, Germany, Hungary, Israel, Italy, Luxembourg, Netherlands, New Zealand, Portugal, Singapore, Spain, Sweden, Switzerland, United Kingdom

Administrative Information

• NCT Number: NCT00182819
• Other Study ID Numbers: EORTC-22033-26033; 2004-002714-11 ( EudraCT Number ); CAN-NCIC-CE5; TROG 06.01; MRC-BR13
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
• Original Responsible Party: Not Provided
• Current Study Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Original Study Sponsor: Same as current

Collaborators

• NCIC Clinical Trials Group
• British Medical Research Council
• Trans Tasman Radiation Oncology Group

Investigators

• Study Chair: Brigitta Baumert, MD, PhD; Maastricht University Medical Center
• Study Chair: Roger Stupp, MD; Centre Hospitalier Universitaire Vaudois

• PRS Account: European Organisation for Research and Treatment of Cancer - EORTC
• Verification Date: October 2016