Effect of Tumor Treating Fields (TTFields, 150kHz) Concomitant with Sorafenib for Advanced Hepatocellular Carcinoma (HCC) (HEPANOVA)

The study is a prospective, phase II trial single arm, historical control aimed to test the efficacy and safety of TTFields, using the NovoTTF-100L(P) System, in combination with sorafenib in patient with advanced HCC. The device is an experimental, portable, battery operated device for chronic administration of alternating electric fields (termed TTFields or TTF) to the region of the malignant tumor, by means of surface, insulated electrode arrays.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

1. HCC diagnosed by biopsy, or by imaging criteria (CT/MRI) and AFP
2. ≥ 18 years of age
3. Barcelona Clinic Liver Cancer Staging (BCLC) Stage 0-C
4. Child-Turcotte-Pugh (CTP) score between 5 and 8 points
5. Measurable disease per RECIST Criteria
6. At least 4 weeks since major surgery
7. ECOG Performance Status (PS) of 0-2
8. Life expectancy of at least 12 weeks
9. All subjects must sign written informed consent
10. Able to operate the NovoTTF-100L(P) System independently or with the help of a caregiver.

Exclusion Criteria:

1. Patient candidate for surgical resection or local treatment (e.g. TACE, SIRT, RFTA, microwave, surgery)
2. High levels of serum HBV DNA without anti-viral therapy
3. Prior malignancy requiring anti-tumor treatment (apart from in-situ cervical cancer, in situ breast cancer, non-melanomatous skin cancers, or any malignancy for which treatment was received and there is no evidence of disease for at least 5 years) or concurrent malignancy.
4. Significant co-morbidities within 4 weeks prior to enrollment, including the following:

   1. neurologic or psychiatric disorders such as dementia and uncontrolled seizures
   2. active, uncontrolled infections
   3. active, disseminated coagulation disorder
   4. Significant renal impairment
   5. Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia)
   6. Chronic diarrhea
   7. History of any psychological or psychiatric condition that might impair the patient's ability to understand or comply with the requirements of the study or to provide consent.
   8. Other co-morbidities deemed by the investigator as such that may impact the compliance of the patient with the study protocol and follow up
5. Implanted pacemaker, defibrillator or other electrical medical devices in the torso
6. Known allergies to medical adhesives or hydrogel
7. Pregnant or breast feeding (all patients of childbearing potential must use effective contraception method during the entire period of the study based on the recommendation of the investigator or a gynecologist)
8. Admitted to an institution by administrative or court order

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• 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
• BACKGROUNDKirson ED, Giladi M, Gurvich Z, Itzhaki A, Mordechovich D, Schneiderman RS, Wasserman Y, Ryffel B, Goldsher D, Palti Y. Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs. Clin Exp Metastasis. 2009;26(7):633-40. doi: 10.1007/s10585-009-9262-y. Epub 2009 Apr 23. PMID 19387848
• BACKGROUNDGiladi M, Schneiderman RS, Voloshin T, Porat Y, Munster M, Blat R, Sherbo S, Bomzon Z, Urman N, Itzhaki A, Cahal S, Shteingauz A, Chaudhry A, Kirson ED, Weinberg U, Palti Y. Mitotic Spindle Disruption by Alternating Electric Fields Leads to Improper Chromosome Segregation and Mitotic Catastrophe in Cancer Cells. Sci Rep. 2015 Dec 11;5:18046. doi: 10.1038/srep18046. PMID 26658786