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

NCT03606590 | Completed Phase 2

• 1 other identifier: EF-30
• Study Type: interventional
• Target: 25
• Locations: 6 countries
• Sites: 8

Brief Summary

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.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular Carcinoma; Treatment; Minimal toxicity; TTFields; Tumor Treating Fields; Novocure; Sorafenib; Nexavar

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  The percentage of patients who had either complete response or partial response per RECIST criteria following enrollment in the trial.

  30 months

Secondary Outcomes (7)

• In-field control rate at one year

  12 months

• Overall survival

  30 months

• Progression Free Survival

  30 months

• Distant metastases-free survival rate at 1 year

  12 months

• Overall survival at one year

  12 months

Study Arms (1)

TTFields in combination with sorafenib

EXPERIMENTAL

Patients will be treated continuously with TTFields, in addition to sorafenib

Device: NovoTTF-100L(P) device; Drug: Sorafenib

Interventions

NovoTTF-100L(P) device DEVICE

Patients will be treated continuously with the NovoTTF-100L(P) device. NovoTTF-100L(P) treatment will consist of wearing four electrically insulated electrode arrays on the abdomen. The treatment enables the patient to maintain regular daily routine.

Also known as: TTFields

TTFields in combination with sorafenib

Sorafenib DRUG

Sorafenib 400 mg (2 x 200 mg tablets) taken twice daily without food (at least 1 hour before or 2 hours after a meal).

Also known as: Nexavar

TTFields in combination with sorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Patient candidate for surgical resection or local treatment (e.g. TACE, SIRT, RFTA, microwave, surgery)
• High levels of serum HBV DNA without anti-viral therapy
• 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.
• Significant co-morbidities within 4 weeks prior to enrollment, including the following:
• neurologic or psychiatric disorders such as dementia and uncontrolled seizures
• active, uncontrolled infections
• active, disseminated coagulation disorder
• Significant renal impairment
• Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia)
• Chronic diarrhea
• 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.
• Other co-morbidities deemed by the investigator as such that may impact the compliance of the patient with the study protocol and follow up
• Implanted pacemaker, defibrillator or other electrical medical devices in the torso
• Known allergies to medical adhesives or hydrogel
• 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)

Sponsors & Collaborators

• NovoCure Ltd.: lead

Study Sites (8)

University Hospital Fakultni Nemocnice Olomouc, Oncology Clinic

Olomouc, 779 00, Czechia

Location

CHU de Nantes

Nantes, 44093, France

Location

University Medical Center - University of Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Ulm University Hospital

Ulm, 89081, Germany

Location

Università Campus Bio-Medico di Roma

Rome, 00128, Italy

Location

Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu

Poznan, 61-701, Poland

Location

Vall d'Hebron Institute of Oncology (VHIO)

Barcelona, Spain

Location

HM Hospitales - Centro Integral Oncológico Clara Campal

Madrid, 28050, Spain

Location

Related Publications (7)

• 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.

  PMID: 15126372 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.

  PMID: 17551011 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.

  PMID: 22608262 BACKGROUND

• Kirson 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 BACKGROUND

• Giladi 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 BACKGROUND

• Stupp R, Taillibert S, Kanner AA, Kesari S, Steinberg DM, Toms SA, Taylor LP, Lieberman F, Silvani A, Fink KL, Barnett GH, Zhu JJ, Henson JW, Engelhard HH, Chen TC, Tran DD, Sroubek J, Tran ND, Hottinger AF, Landolfi J, Desai R, Caroli M, Kew Y, Honnorat J, Idbaih A, Kirson ED, Weinberg U, Palti Y, Hegi ME, Ram Z. Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial. JAMA. 2015 Dec 15;314(23):2535-43. doi: 10.1001/jama.2015.16669.

  PMID: 26670971 BACKGROUND

• Stupp R, Taillibert S, Kanner A, Read W, Steinberg D, Lhermitte B, Toms S, Idbaih A, Ahluwalia MS, Fink K, Di Meco F, Lieberman F, Zhu JJ, Stragliotto G, Tran D, Brem S, Hottinger A, Kirson ED, Lavy-Shahaf G, Weinberg U, Kim CY, Paek SH, Nicholas G, Bruna J, Hirte H, Weller M, Palti Y, Hegi ME, Ram Z. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA. 2017 Dec 19;318(23):2306-2316. doi: 10.1001/jama.2017.18718.

  PMID: 29260225 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2018
• First Posted: July 31, 2018
• Study Start: February 15, 2019
• Primary Completion: January 14, 2021
• Study Completion: January 14, 2021
• Last Updated: November 14, 2024

Record last verified: 2024-11

Locations

IT (1); PL (1); FR (1); CZ (1); DE (2); ES (2)