Post-approval Study of NovoTTF-100A in Recurrent GBM Patients

This is a non-randomized, concurrent control study, designed to confirm that the efficacy of the NovoTTF-100A System in patients with recurrent GBM treated in a real life settings following approval is comparable to that of BSC chemotherapy patients. The device is a portable, battery operated device that was approved for the treatment of adult patients (22 years of age or older) with histologically-confirmed glioblastoma multiforme (GBM), following histologically- or radiologically-confirmed recurrence in the supra-tentorial region of the brain after receiving chemotherapy. The device is intended to be used as a monotherapy, and is intended as an alternative to standard medical therapy for GBM after surgical and radiation options have been exhausted.

Sex

All

Minimum age

22 Years

Inclusion Criteria:

1. 22 years of age or older
2. Histological diagnosis of GBM (WHO grade IV)
3. Tumor located in the supra-tentorial region of the brain
4. Received maximal, safe, surgical resection
5. Received maximal radiation therapy
6. Received concomitant Temozolomide
7. Received maintenance Temozolomide
8. First recurrence (based on radiological or histological evidence of recurrence)
9. Karnofsky performance score 70 or above
10. MMSE score 25 or above
11. Adequate amount and quality of tumor tissue from first surgical resection available for genetic profiling
12. Women of childbearing age must be on effective contraception
13. Signed informed consent
14. Stable steroid dose in past 4 weeks

Exclusion Criteria:

1. Implanted electronic medical device in the brain:

   1. Deep brain stimulator
   2. Vagus nerve stimulator
   3. Programmable shunt
2. Skull defect without replacement
3. Unable to comply with treatment with the NovoTTF-100A device
4. Pregnant
5. Prior antiangiogenic therapy (e.g., Bevacizumab/Avastin)
6. Second or subsequent recurrence
7. Any prior cytotoxic chemotherapy except Temozolomide
8. Actively participating in another therapeutic clinical trial
9. Radiological suspicion of pseudoprogression or radionecrosis
10. Radiation therapy or surgery in the past 4 weeks
11. Unable to comply with the study follow-up schedule
12. Any serious co-morbidity which is expected to affect survival more adversely than GBM

• 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
• BACKGROUNDStupp 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
• DERIVEDZhu JJ, Goldlust SA, Kleinberg LR, Honnorat J, Oberheim Bush NA, Ram Z. Tumor Treating Fields (TTFields) therapy vs physicians' choice standard-of-care treatment in patients with recurrent glioblastoma: a post-approval registry study (EF-19). Discov Oncol. 2022 Oct 14;13(1):105. doi: 10.1007/s12672-022-00555-5. PMID 36239858