Whole Brain Radiotherapy Versus Volumetric Modulated Arc Therapy for Brain Metastases

NCT02220491 | Completed

• 1 other identifier: H14-02032
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with brain metastases with expected life expectancy of 3-6 months are typically treated with radiotherapy to the whole brain giving a dose of 20 Gy over a 5 day period. This study will compare this with volumetric modulated arc therapy (VMAT) which is capable of delivering 15 Gy in one single session to identified disease within the brain but sparing the normal surrounding brain tissue. Primarily the study will assess whether it is possible to recruit sufficient patient numbers to a trial of this type. It will also compare effectiveness, side effects and quality of life between the two treatment methods.

Conditions

Brain Metastases

Outcome Measures

Primary Outcomes (1)

• Accrual

  The time of accrual of 20 subjects will be recorded in months from the official study opening at each cancer centre until the 20th patient is accrued. The rate of accrual will be calculated by dividing the number of patients by the number of months it took to accrue them

  8 months

Secondary Outcomes (1)

• Intracranial disease control

  3 months

Other Outcomes (7)

• Compare the use of corticosteroids

  Every 4 weeks for 1 year

• Compare the incidence of retreatment with cranial radiotherapy

  3 months

• Compare the incidence of acute and late side effects

  6 weeks, 3 months, 6 months, 9 months, 12 months

Study Arms (2)

Whole-brain radiotherapy

ACTIVE COMPARATOR

All subjects will have a non-contrast CT scan using a slice thickness of 2.5mm or less. The Brain contour will be generated using the segmentation wizard and edits as required. PTV\_Brain is an expansion of the Brain by 5mm. 99% of PTV\_Brain is to be covered by 95% of 20 Gy in 5 fractions using 6-10 MV photons in a parallel-opposed pair lateral beam arrangement.

Radiation: Whole-brain radiotherapy

Single-fraction radiotherapy

EXPERIMENTAL

Immobilized in the mask, the subject will be imaged for radiotherapy planning with a CT slice thickness of 1.25 mm or less and an axial resolution of \< 0.7 mm (CT field of view \< 35 cm). Subjects that require contrast with GFR 45-59 will have pre-hydration, contrast dose modification and/or Mucomyst administration to preserve renal function, according to standard practice for radiological imaging at the institution.

Radiation: Single-fraction radiotherapy

Interventions

Single-fraction radiotherapy RADIATION

Volumetric modulated arc therapy (VMAT) delivering 15 Gy in one fraction to brain metastases

Single-fraction radiotherapy

Whole-brain radiotherapy RADIATION

Whole brain radiotherapy delivering 20 Gy in five fractions to brain metastases

Whole-brain radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18
• Pathologically confirmed solid malignancy
• brain or brainstem metastases on MRI with a maximum of 4 cm diameter
• Documented extracranial disease
• Anticipated median survival 3-6 months (Graded Prognostic Assessment: Appendix I)
• Available for regular clinical and imaging follow up (\< 1 hour from a cancer centre)
• Montreal Cognitive Assessment score ≥ 20 (Appendix II)
• Karnofsky Performance Score (KPS) ≥ 70 (Appendix III)
• Barthel Activities of Daily Living score ≥ 90 (Appendix IV)
• Able to complete EORTC quality of life questionnaires (Appendix V)

You may not qualify if:

• A metastasis located within 5 mm of the optic nerves or optic chiasm
• Requiring craniotomy to relieve mass effect
• Cytotoxic systemic therapy administered within one week before radiotherapy or planned within one week after radiotherapy
• Neurological decline since starting corticosteroids
• Metastatic germinoma, small cell carcinoma, multiple myeloma, lymphoma or leukaemia
• Systemic lupus erythematosis, scleroderma, or other connective tissue disorders not in remission
• Multiple sclerosis
• Glomerular Filtration Rate \< 45 ml/minute
• Contra-indications to MRI
• Pregnancy
• AST, ALT or Bilirubin \> 3 times upper limit of normal
• Haemorrhagic Metastases

Sponsors & Collaborators

• British Columbia Cancer Agency: lead

Study Sites (1)

British Columbia Cancer Agency

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Related Publications (21)

• Mekhail T, Sombeck M, Sollaccio R. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. Curr Oncol Rep. 2011 Aug;13(4):255-8. doi: 10.1007/s11912-011-0180-1. No abstract available.

  PMID: 21584645 BACKGROUND

• Soon YY, Tham IW, Lim KH, Koh WY, Lu JJ. Surgery or radiosurgery plus whole brain radiotherapy versus surgery or radiosurgery alone for brain metastases. Cochrane Database Syst Rev. 2014 Mar 1;2014(3):CD009454. doi: 10.1002/14651858.CD009454.pub2.

  PMID: 24585087 BACKGROUND

• Soffietti R, Kocher M, Abacioglu UM, Villa S, Fauchon F, Baumert BG, Fariselli L, Tzuk-Shina T, Kortmann RD, Carrie C, Ben Hassel M, Kouri M, Valeinis E, van den Berge D, Mueller RP, Tridello G, Collette L, Bottomley A. A European Organisation for Research and Treatment of Cancer phase III trial of adjuvant whole-brain radiotherapy versus observation in patients with one to three brain metastases from solid tumors after surgical resection or radiosurgery: quality-of-life results. J Clin Oncol. 2013 Jan 1;31(1):65-72. doi: 10.1200/JCO.2011.41.0639. Epub 2012 Dec 3.

  PMID: 23213105 BACKGROUND

• Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, Arbuckle RB, Swint JM, Shiu AS, Maor MH, Meyers CA. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009 Nov;10(11):1037-44. doi: 10.1016/S1470-2045(09)70263-3. Epub 2009 Oct 2.

  PMID: 19801201 BACKGROUND

• Rodrigues G, Warner A, Zindler J, Slotman B, Lagerwaard F. A clinical nomogram and recursive partitioning analysis to determine the risk of regional failure after radiosurgery alone for brain metastases. Radiother Oncol. 2014 Apr;111(1):52-8. doi: 10.1016/j.radonc.2013.11.015. Epub 2014 Jan 17.

  PMID: 24444529 BACKGROUND

• Tsao MN, Lloyd N, Wong RK, Chow E, Rakovitch E, Laperriere N, Xu W, Sahgal A. Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases. Cochrane Database Syst Rev. 2012 Apr 18;2012(4):CD003869. doi: 10.1002/14651858.CD003869.pub3.

  PMID: 22513917 BACKGROUND

• Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, Werner-Wasik M, Demas W, Ryu J, Bahary JP, Souhami L, Rotman M, Mehta MP, Curran WJ Jr. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004 May 22;363(9422):1665-72. doi: 10.1016/S0140-6736(04)16250-8.

  PMID: 15158627 BACKGROUND

• Shaw E, Scott C, Souhami L, Dinapoli R, Bahary JP, Kline R, Wharam M, Schultz C, Davey P, Loeffler J, Del Rowe J, Marks L, Fisher B, Shin K. Radiosurgery for the treatment of previously irradiated recurrent primary brain tumors and brain metastases: initial report of radiation therapy oncology group protocol (90-05). Int J Radiat Oncol Biol Phys. 1996 Feb 1;34(3):647-54. doi: 10.1016/0360-3016(95)02106-x.

  PMID: 8621289 BACKGROUND

• Yamamoto M, Serizawa T, Shuto T, Akabane A, Higuchi Y, Kawagishi J, Yamanaka K, Sato Y, Jokura H, Yomo S, Nagano O, Kenai H, Moriki A, Suzuki S, Kida Y, Iwai Y, Hayashi M, Onishi H, Gondo M, Sato M, Akimitsu T, Kubo K, Kikuchi Y, Shibasaki T, Goto T, Takanashi M, Mori Y, Takakura K, Saeki N, Kunieda E, Aoyama H, Momoshima S, Tsuchiya K. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol. 2014 Apr;15(4):387-95. doi: 10.1016/S1470-2045(14)70061-0. Epub 2014 Mar 10.

  PMID: 24621620 BACKGROUND

• Clark GM, Popple RA, Young PE, Fiveash JB. Feasibility of single-isocenter volumetric modulated arc radiosurgery for treatment of multiple brain metastases. Int J Radiat Oncol Biol Phys. 2010 Jan 1;76(1):296-302. doi: 10.1016/j.ijrobp.2009.05.029.

  PMID: 19836151 BACKGROUND

• Stieler F, Fleckenstein J, Simeonova A, Wenz F, Lohr F. Intensity modulated radiosurgery of brain metastases with flattening filter-free beams. Radiother Oncol. 2013 Dec;109(3):448-51. doi: 10.1016/j.radonc.2013.10.017. Epub 2013 Nov 11.

  PMID: 24231243 BACKGROUND

• Audet C, Poffenbarger BA, Chang P, Jackson PS, Lundahl RE, Ryu SI, Ray GR. Evaluation of volumetric modulated arc therapy for cranial radiosurgery using multiple noncoplanar arcs. Med Phys. 2011 Nov;38(11):5863-72. doi: 10.1118/1.3641874.

  PMID: 22047350 BACKGROUND

• Karnofsky DA, Burchenal JH. The clinical evaluation of chemotherapeutic agents in cancer. In: MacLeod CM, editor. Evaluation of Chemotherapeutic Agents. Columbia University Press; 1949. p. 196.

  BACKGROUND

• Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x.

  PMID: 15817019 BACKGROUND

• Shah S, Vanclay F, Cooper B. Improving the sensitivity of the Barthel Index for stroke rehabilitation. J Clin Epidemiol. 1989;42(8):703-9. doi: 10.1016/0895-4356(89)90065-6.

  PMID: 2760661 BACKGROUND

• Taphoorn MJ, Claassens L, Aaronson NK, Coens C, Mauer M, Osoba D, Stupp R, Mirimanoff RO, van den Bent MJ, Bottomley A; EORTC Quality of Life Group, and Brain Cancer, NCIC and Radiotherapy Groups. An international validation study of the EORTC brain cancer module (EORTC QLQ-BN20) for assessing health-related quality of life and symptoms in brain cancer patients. Eur J Cancer. 2010 Apr;46(6):1033-40. doi: 10.1016/j.ejca.2010.01.012. Epub 2010 Feb 22.

  PMID: 20181476 BACKGROUND

• Caissie A, Nguyen J, Chen E, Zhang L, Sahgal A, Clemons M, Kerba M, Arnalot PF, Danjoux C, Tsao M, Barnes E, Holden L, Danielson B, Chow E. Quality of life in patients with brain metastases using the EORTC QLQ-BN20+2 and QLQ-C15-PAL. Int J Radiat Oncol Biol Phys. 2012 Jul 15;83(4):1238-45. doi: 10.1016/j.ijrobp.2011.09.025. Epub 2011 Dec 13.

  PMID: 22172909 BACKGROUND

• Groenvold M, Petersen MA, Aaronson NK, Arraras JI, Blazeby JM, Bottomley A, Fayers PM, de Graeff A, Hammerlid E, Kaasa S, Sprangers MA, Bjorner JB; EORTC Quality of Life Group. The development of the EORTC QLQ-C15-PAL: a shortened questionnaire for cancer patients in palliative care. Eur J Cancer. 2006 Jan;42(1):55-64. doi: 10.1016/j.ejca.2005.06.022. Epub 2005 Sep 12.

  PMID: 16162404 BACKGROUND

• Hsieh YW, Wang CH, Wu SC, Chen PC, Sheu CF, Hsieh CL. Establishing the minimal clinically important difference of the Barthel Index in stroke patients. Neurorehabil Neural Repair. 2007 May-Jun;21(3):233-8. doi: 10.1177/1545968306294729. Epub 2007 Mar 9.

  PMID: 17351082 BACKGROUND

• Sperduto PW, Chao ST, Sneed PK, Luo X, Suh J, Roberge D, Bhatt A, Jensen AW, Brown PD, Shih H, Kirkpatrick J, Schwer A, Gaspar LE, Fiveash JB, Chiang V, Knisely J, Sperduto CM, Mehta M. Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4,259 patients. Int J Radiat Oncol Biol Phys. 2010 Jul 1;77(3):655-61. doi: 10.1016/j.ijrobp.2009.08.025. Epub 2009 Nov 26.

  PMID: 19942357 BACKGROUND

• Raman S, Mou B, Hsu F, Valev B, Cheung A, Vallieres I, Ma R, McKenzie M, Beaton L, Rackley T, Gondara L, Nichol A. Whole Brain Radiotherapy Versus Stereotactic Radiosurgery in Poor-Prognosis Patients with One to 10 Brain Metastases: A Randomised Feasibility Study. Clin Oncol (R Coll Radiol). 2020 Jul;32(7):442-451. doi: 10.1016/j.clon.2020.02.001. Epub 2020 Feb 19.

  PMID: 32085923 DERIVED

MeSH Terms

Conditions

Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Nichol Alan, MD

  British Columbia Cancer Agency

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2014
• First Posted: August 20, 2014
• Study Start: October 1, 2014
• Primary Completion: May 18, 2020
• Study Completion: May 18, 2020
• Last Updated: May 20, 2020

Record last verified: 2020-05

Locations

CA (1)