Advances in Therapy

, Volume 28, Issue 4, pp 334–340 | Cite as

AVAglio: Phase 3 trial of bevacizumab plus temozolomide and radiotherapy in newly diagnosed glioblastoma multiforme

  • O. L. Chinot
  • T. de La Motte Rouge
  • N. Moore
  • A. Zeaiter
  • A. Das
  • H. Phillips
  • Z. Modrusan
  • T. Cloughesy
Open Access


Despite treatment with the current standard-of-care therapies, patients with newly diagnosed glioblastoma multiforme (GBM) exhibit dismal prognoses. Bevacizumab has demonstrated activity in patients with recurrent GBM and phase 2 trials indicate that the combination of bevacizumab with standard-of-care therapy is feasible and active for patients with newly diagnosed GBM. Bevacizumab has been granted US approval for use as single-agent therapy for patients with progressive GBM following prior therapy, although it has not received approval for use in patients with GBM in Europe. Phase 3 studies have been initiated in patients with newly diagnosed GBM and are currently recruiting patients. We describe the protocol for the AVAglio phase 3 registration trial, which is designed to evaluate the efficacy and safety of combining bevacizumab with standard-of-care therapy in patients with newly diagnosed GBM.


bevacizumab clinical trial glioblastoma multiforme phase 3 


  1. 1.
    Adamson C, Kanu OO, Mehta AI, et al. Glioblastoma mutliforme: a review of where we have been and where we are going. Expert Opin Investig Drugs. 2009;18:1061–1083.PubMedCrossRefGoogle Scholar
  2. 2.
    Ohgaki H. Epidemiology of brain tumors. Methods Mol Biol. 2009;472:323–342.PubMedCrossRefGoogle Scholar
  3. 3.
    Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10:459–466.PubMedCrossRefGoogle Scholar
  4. 4.
    Yang JC, Haworth L, Sherry RM, et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med. 2003;349:427–434.PubMedCrossRefGoogle Scholar
  5. 5.
    Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–2342.PubMedCrossRefGoogle Scholar
  6. 6.
    Sandler A, Gray R, Perry MC, et al. Paclitaxelcarboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006;355:2542–2550.PubMedCrossRefGoogle Scholar
  7. 7.
    Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007;357:2666–2676.PubMedCrossRefGoogle Scholar
  8. 8.
    Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev. 2004;25:581–611.PubMedCrossRefGoogle Scholar
  9. 9.
    Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005;23:1011–1127.PubMedCrossRefGoogle Scholar
  10. 10.
    Gerber HP, Ferrara N. Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies. Cancer Res. 2005;65:671–680.PubMedGoogle Scholar
  11. 11.
    Mathieu V, De Neve N, Le Mercier M, et al. Combining bevacizumab with temozolomide increases the antitumor efficacy of temozolomide in a human glioblastoma orthotopic xenograft model. Neoplasia. 2008;10:1383–1392.PubMedGoogle Scholar
  12. 12.
    Lee CG, Heijn M, di Tomaso E, et al. Anti-vascular endothelial growth factor treatment augments tumour radiation response under normoxic or hypoxic conditions. Cancer Res. 2000;60:5565–5570.PubMedGoogle Scholar
  13. 13.
    Vredenburgh JJ, Desjardins A, Herndon JE 2nd, et al. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol. 2007;25:4722–4729.PubMedCrossRefGoogle Scholar
  14. 14.
    Kreisl TN, Kim L, Moore K, et al. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 2009;27:740–745.PubMedCrossRefGoogle Scholar
  15. 15.
    Friedman HS, Prados MD, Wen PY, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009;27:4733–4740.PubMedCrossRefGoogle Scholar
  16. 16.
    Vredenburgh JJ, Wefel J, Coughesy T, et al. Clinical assessment of corticosteroid use and neurocognitive function in patients with glioblastoma at first or second relapse treated with bevacizumab in the BRAIN study. Eur J Cancer Suppl. 2009;7:495 (abstract O-8701).CrossRefGoogle Scholar
  17. 17.
    Lai A, Filka E, McGibbon B, et al. Phase II pilot study of bevacizumab in combination with temozolomide and regional radiation therapy for up-front treatment of patients with newly diagnosed glioblastoma multiforme: interim analysis of safety and tolerability. Int J Radiat Oncol Biol Phys. 2008;71:1372–1380.PubMedCrossRefGoogle Scholar
  18. 18.
    Narayana A, Golfinos JG, Fischer I, et al. Feasibility of using bevacizumab with radiation therapy and temozolomide in newly diagnosed high-grade glioma. Int J Radiat Oncol Biol Phys. 2008;72:383–389.PubMedCrossRefGoogle Scholar
  19. 19.
    Lai A, Tran A Nghiemphu PL, et al. Phase II trial of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme. J Clin Oncol. 2011;29:142–148.PubMedCrossRefGoogle Scholar
  20. 20.
    Gruber ML, Raza S, Gruber D, Narayana A. Bevacizumab in combination with radiotherapy plus concomitant and adjuvant temozolomide for newly diagnosed glioblastoma: update progressionfree survival, overall survival, and toxicity. J Clin Oncol. 2009;27(Suppl):15s (abstract 2017).Google Scholar
  21. 21.
    Anon. A study of Avastin (bevacizumab) in combination with temozolomide and radiotherapy in patients with newly diagnosed glioblastoma. Available at: Accessed July 14, 2010.
  22. 22.
    Chinot O, de La Motte Rouge T, Moore N, Zeaiter A. Addition of bevacizumab to the multi-modality standard care in patients with newly diagnosed glioblastoma: a phase III trial. Poster presented at: 34th ESMO Multidisciplinary Congress, September 20–24, 2009; Berlin, Germany.Google Scholar
  23. 23.
    Wen PY, Macdonald DR, Reardon DA, et al. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010;28:1963–1972.PubMedCrossRefGoogle Scholar
  24. 24.
    Lucio-Eterovic AK, Piao Y, de Groot JF. Mediators of glioblastoma resistance and invasion during antivascular endothelial growth factor therapy. Clin Cancer Res. 2009;15:4589–4599.PubMedCrossRefGoogle Scholar
  25. 25.
    Pope WB, Xia Q, Paton VE, et al. Patterns of progression in patients with recurrent glioblastoma treated with bevacizumab. Neurology. 2011;76:432–437.PubMedCrossRefGoogle Scholar
  26. 26.
    Wick W, Wick A, Weiler M, Weller M. Patterns of progression in malignant glioma following anti-VEGF therapy: perceptions and evidence. Curr Neurol Neurosci Rep. In press.Google Scholar
  27. 27.
    Anon. Temozolomide and radiation therapy with or without bevacizumab in treating patients with newly diagnosed glioblastoma or gliosarcoma. Available at: Accessed July 14, 2010.

Copyright information

© Springer Healthcare 2011

Authors and Affiliations

  • O. L. Chinot
    • 1
  • T. de La Motte Rouge
    • 2
  • N. Moore
    • 3
  • A. Zeaiter
    • 3
  • A. Das
    • 4
  • H. Phillips
    • 4
  • Z. Modrusan
    • 4
  • T. Cloughesy
    • 5
  1. 1.Service de Neuro-Oncologie, Centre Hospitalo-Universitaire TimoneUniversité de la MéditerranéeMarseilles Cedex 05France
  2. 2.Service d’Oncologie MédicaleGroupe Hospitalier Pitié SalpétrièreParisFrance
  3. 3.F. Hoffmann-La Roche Ltd.BaselSwitzerland
  4. 4.Genentech, Inc.San FranciscoUSA
  5. 5.David Geffen School of MedicineUniversity of CaliforniaLos AngelesUSA

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