Effect of NovoTTF-100A in Recurrent Glioblastoma Multiforme (GBM)

The study is a randomized, controlled trial, designed to test the efficacy and safety of a new medical device, the NovoTTF-100A. The device is an experimental, portable, battery operated device for chronic treatment of patients with recurrent or progressive glioblastoma multiforme (GBM) using alternating electric fields (termed TTFields).

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Pathological evidence of GBM using WHO classification criteria.
* \> 18 years of age.
* Not a candidate for further radiotherapy or additional resection of residual tumor.
* Patients with disease progression (by Macdonald criteria i.e., \> 25% or new lesion) documented by CT or MRI within 4 weeks prior to enrollment
* Karnofsky scale ≥ 70
* Life expectancy at least 3 months
* Participants of childbearing age must use effective contraception.
* All patients must sign written informed consent.

Exclusion Criteria:

* Actively participating in another clinical treatment trial
* Within 4 weeks from surgery for recurrence
* Within 4 weeks from any prior chemotherapy.
* Within 4 weeks from radiation therapy
* Pregnant
* Significant co-morbidities (within 4 weeks prior to enrollment):

  1. Significant liver function impairment - AST or ALT \> 3 times the upper limit of normal
  2. Total bilirubin \> upper limit of normal
  3. Significant renal impairment (serum creatinine \> 1.7 mg/dL)
  4. Coagulopathy (as evidenced by PT or APTT \>1.5 times control in patients not undergoing anticoagulation)
  5. Thrombocytopenia (platelet count \< 100 x 103/μL)
  6. Neutropenia (absolute neutrophil count \< 1 x 103/μL)
  7. Anemia (Hb \< 10 g/L)
  8. Severe acute infection
* Implanted pacemaker, defibrillator or deep brain stimulator, or documented clinically significant arrhythmias.
* Infra-tentorial tumor
* Evidence of increased intracranial pressure (midline shift \> 5mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness)

• BACKGROUNDKirson 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. PMID 15126372
• BACKGROUNDKirson 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. PMID 17551011
• BACKGROUNDSalzberg M, Kirson E, Palti Y, Rochlitz C. A pilot study with very low-intensity, intermediate-frequency electric fields in patients with locally advanced and/or metastatic solid tumors. Onkologie. 2008 Jul;31(7):362-5. doi: 10.1159/000137713. Epub 2008 Jun 24. PMID 18596382
• DERIVEDStupp 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. PMID 22608262