NovoTTF-200A and Temozolomide Chemoradiation for Newly Diagnosed Glioblastoma

Summary

This study is a prospective single arm trial designed to study the safety, feasibility and preliminary efficacy of a medical device, NovoTTF-200A used concomitantly with standard adjuvant treatment for newly diagnosed glioblastoma.

Timeline

Start

2017-07-26

Primary completion

2022-12-07

Completion

2022-12-07

Publications

• Background Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups; National Cancer Institute of Canada Clinical Trials Group. 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 May;10(5):459-66. doi: 10.1016/S1470-2045(09)70025-7. Epub 2009 Mar 9.
• Background Polk C. Therapeutic applications of low-frequency sinusoidal and pulsed electric and magnetic fields. In: Bronzino JD ed. The biomedical engineering handbook. Connecticut: CRC Press, 1995:1404-1416.
• Background Palti Y. Stimulation of internal organs by means of externally applied electrodes. J Appl Physiol. 1966 Sep;21(5):1619-23. doi: 10.1152/jappl.1966.21.5.1619. No abstract available.
• Background Bassett CA. The development and application of pulsed electromagnetic fields (PEMFs) for ununited fractures and arthrodeses. Clin Plast Surg. 1985 Apr;12(2):259-77.
• Background Elson E. Biologic Effects of radiofrequency and microwave fields: in vivo and in vitro experimental results. In: Bronzino JD ed. The biomedical engineering handbook. Connecticut: CRC Press, 1995:1417-1423.
• Background Chou CK. Radiofrequency hyperthermia in cancer therapy. In: Bronzino JD ed. The biomedical engineering handbook. Connecticut: CRC Press, 1995:1424-1430.
• Background Takashima S, Schwan HP. Alignment of microscopic particles in electric fields and its biological implications. Biophys J. 1985 Apr;47(4):513-8. doi: 10.1016/S0006-3495(85)83945-X.
• Background Zimmermann U, Vienken J, Pilwat G. Rotation of cells in an alternating electric field: the occurrence of a resonance frequency. Z Naturforsch C Biosci. 1981 Jan-Feb;36(1-2):173-7. doi: 10.1515/znc-1981-1-229.
• Background Holzapfel C, Vienken J, Zimmermann U. Rotation of cells in an alternating electric field: theory and experimental proof. J Membr Biol. 1982;67(1):13-26. doi: 10.1007/BF01868644.
• Background Pawlowski P, Szutowicz I, Marszalek P, Fikus M. Bioelectrorheological model of the cell. 5. Electrodestruction of cellular membrane in alternating electric field. Biophys J. 1993 Jul;65(1):541-9. doi: 10.1016/S0006-3495(93)81056-7.
• Background Kirson ED, Gurvich Z, Schneiderman R, Dekel E, Itzhaki A, Wasserman Y, Schatzberger R, Palti Y. Disruption of cancer cell replication by alternating electric fields. Cancer Res. 2004 May 1;64(9):3288-95. doi: 10.1158/0008-5472.can-04-0083.
• Background Zhao M, Forrester JV, McCaig CD. A small, physiological electric field orients cell division. Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):4942-6. doi: 10.1073/pnas.96.9.4942.
• Background Jordan MA, Thrower D, Wilson L. Effects of vinblastine, podophyllotoxin and nocodazole on mitotic spindles. Implications for the role of microtubule dynamics in mitosis. J Cell Sci. 1992 Jul;102 ( Pt 3):401-16. doi: 10.1242/jcs.102.3.401.
• Background Rowinsky EK, Donehower RC. Paclitaxel (taxol). N Engl J Med. 1995 Apr 13;332(15):1004-14. doi: 10.1056/NEJM199504133321507. No abstract available.
• Background Kline-Smith SL, Walczak CE. The microtubule-destabilizing kinesin XKCM1 regulates microtubule dynamic instability in cells. Mol Biol Cell. 2002 Aug;13(8):2718-31. doi: 10.1091/mbc.e01-12-0143.
• Background Kapoor TM, Mayer TU, Coughlin ML, Mitchison TJ. Probing spindle assembly mechanisms with monastrol, a small molecule inhibitor of the mitotic kinesin, Eg5. J Cell Biol. 2000 Sep 4;150(5):975-88. doi: 10.1083/jcb.150.5.975.
• Background Maiato H, Sampaio P, Lemos CL, Findlay J, Carmena M, Earnshaw WC, Sunkel CE. MAST/Orbit has a role in microtubule-kinetochore attachment and is essential for chromosome alignment and maintenance of spindle bipolarity. J Cell Biol. 2002 May 27;157(5):749-60. doi: 10.1083/jcb.200201101. Epub 2002 May 28.
• Background Gagliardi LJ. Electrostatic force in prometaphase, metaphase, and anaphase-A chromosome motions. Phys Rev E Stat Nonlin Soft Matter Phys. 2002 Jul;66(1 Pt 1):011901. doi: 10.1103/PhysRevE.66.011901. Epub 2002 Jul 12.
• Background Fishkind DJ, Silverman JD, Wang YL. Function of spindle microtubules in directing cortical movement and actin filament organization in dividing cultured cells. J Cell Sci. 1996 Aug;109 ( Pt 8):2041-51. doi: 10.1242/jcs.109.8.2041.
• Background Dogterom M, Yurke B. Measurement of the force-velocity relation for growing microtubules. Science. 1997 Oct 31;278(5339):856-60. doi: 10.1126/science.278.5339.856.
• Background Kirson ED, Dbaly V, Tovarys F, Vymazal J, Soustiel JF, Itzhaki A, Mordechovich D, Steinberg-Shapira S, Gurvich Z, Schneiderman R, Wasserman Y, Salzberg M, Ryffel B, Goldsher D, Dekel E, Palti Y. Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors. Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10152-7. doi: 10.1073/pnas.0702916104. Epub 2007 Jun 5.
• Background Kirson ED, Schneiderman RS, Dbaly V, Tovarys F, Vymazal J, Itzhaki A, Mordechovich D, Gurvich Z, Shmueli E, Goldsher D, Wasserman Y, Palti Y. Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields). BMC Med Phys. 2009 Jan 8;9:1. doi: 10.1186/1756-6649-9-1.
• Background Stupp R, Wong E, Scott C et al. Interim analysis of the EF-14 trial: a prospective, multi-center trial of NovoTTF-100A together with temozolomide compared to temozolomide alone in patients with newly diagnosed GBM. Neuro Oncol 2014;16(suppl 5):v167.
• Background Stupp R, Wong ET, Kanner AA, Steinberg D, Engelhard H, Heidecke V, Kirson ED, Taillibert S, Liebermann F, Dbaly V, Ram Z, Villano JL, Rainov N, Weinberg U, Schiff D, Kunschner L, Raizer J, Honnorat J, Sloan A, Malkin M, Landolfi JC, Payer F, Mehdorn M, Weil RJ, Pannullo SC, Westphal M, Smrcka M, Chin L, Kostron H, Hofer S, Bruce J, Cosgrove R, Paleologous N, Palti Y, Gutin PH. NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer. 2012 Sep;48(14):2192-202. doi: 10.1016/j.ejca.2012.04.011. Epub 2012 May 18.
• Background Pless M, Droege C, von Moos R, Salzberg M, Betticher D. A phase I/II trial of Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer. Lung Cancer. 2013 Sep;81(3):445-450. doi: 10.1016/j.lungcan.2013.06.025. Epub 2013 Jul 23.
• Background Giladi M, Zielinska-Chomej K, Tichon A et al. The effect of alternating electric fields (TTFields) on inhibition of repair of DNA damage induced by ionizing radiation and sensitization of glioma and non-small cell lung cancer cells to radiation. J Clin Oncol 2014;32(suppl;abstr e22239).
• Background Zielinska-Chomej K, Grozman V, Tu J, Viktorsson K, Lewensohn R. Analysis of combination of tumor treating fields (TTFields) with radiotherapy in non-small cell lung cancer. Neuro Oncol 2013;15(suppl 3):ET-033.
• Background Lacouture ME, Davis ME, Elzinga G, Butowski N, Tran D, Villano JL, DiMeglio L, Davies AM, Wong ET. Characterization and management of dermatologic adverse events with the NovoTTF-100A System, a novel anti-mitotic electric field device for the treatment of recurrent glioblastoma. Semin Oncol. 2014 Jun;41 Suppl 4:S1-14. doi: 10.1053/j.seminoncol.2014.03.011. Epub 2014 Mar 19.

Drugs

Indications