Effect of Tumor Treating Fields (TTFields, 150 kHz) as Front-Line Treatment of Locally-advanced Pancreatic Adenocarcinoma Concomitant With Gemcitabine and Nab-paclitaxel (PANOVA-3)

Pancreas Adenocarcinoma Clinical Trial

Official title:

Pivotal, Randomized, Open-label Study of Tumor Treating Fields (TTFields, 150kHz) Concomitant With Gemcitabine and Nab-paclitaxel for Front-line Treatment of Locally-advanced Pancreatic Adenocarcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03377491
• Other study ID #: EF-27
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 10, 2018
• Est. completion date: October 30, 2024

Study information

• Verified date: April 2023
• Source: NovoCure Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Brief Summary: The study is a prospective, randomized controlled phase III trial aimed to test the efficacy and safety of Tumor Treating Fields (TTFields) in combination with gemcitabine and nab-paclitaxel, for front line treatment of locally-advanced pancreatic adenocarcinoma.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.

Description:

PAST PRE-CLINICAL AND CLINICAL EXPERIENCE: The effect of the electric fields (TTFields, TTF) has demonstrated significant activity in in vitro and in vivo pancreatic adenocarcinoma pre-clinical models both as a single modality treatment and in combination with chemotherapies. TTFields have been demonstrated to act synergistically with taxanes and have been shown to be additive when combined with other chemotherapies including gemcitabine. In addition, TTFields have shown to inhibit metastatic spread of malignant melanoma in in vivo experiment. In a pilot study, 40 patients with locally advanced or metastatic pancreatic adenocarcinoma received gemcitabine together with TTFields (150 kHz) or gemcitabine and nab-paclitaxel together with TTFields (150 kHz) applied to the abdomen until disease progression. The combination was well tolerated and the only device-related adverse event was contact dermatitis. In addition, a phase III trial of Optune® (200 kHz) as monotherapy compared to active chemotherapy in recurrent glioblastoma patients showed TTFields to be equivalent to active chemotherapy in extending survival, associated with minimal toxicity, good quality of life, and activity within the brain (14% response rate) (Stupp R., et al., EJC 2012). Finally, a phase III trial of Optune® combined with maintenance temozolomide compared to maintenance temozolomide alone has shown that combined therapy led to a significant improvement in both progression free survival and overall survival in patients with newly diagnosed glioblastoma without the addition of high grade toxicity and without decline in quality of life (Stupp R., et al., JAMA 2017). DESCRIPTION OF THE TRIAL: All patients included in this trial are patients with locally advanced pancreatic adenocarcinoma. In addition, all patients must meet all eligibility criteria. Eligible patients will be randomly assigned to one of two groups: 1. Patients receive gemcitabine and nab-paclitaxel in combination with TTFields using the NovoTTF-200T System. 2. Patients receive gemcitabine and nab-paclitaxel without TTFields. Patients will be randomized at a 1:1 ratio. Baseline tests will be performed in patients enrolled in both arms. If assigned to the NovoTTF-200T group, the patients will be treated continuously with the device until progression in the abdomen. On both arms, patients who have progression outside the abdomen will switch to a second line treatment according to local practice. SCIENTIFIC BACKGROUND: Electric fields exert forces on electric charges similar to the way a magnet exerts forces on metallic particles within a magnetic field. These forces cause movement and rotation of electrically charged biological building blocks, much like the alignment of metallic particles seen along the lines of force radiating outwards from a magnet. Electric fields can also cause muscles to twitch and if strong enough may heat tissues. TTFields are alternating electric fields of low intensity. This means that they change their direction repetitively many times a second. Since they change direction very rapidly (150 thousand times a second), they do not cause muscles to twitch, nor do they have any effects on other electrically activated tissues in the body (brain, nerves and heart). Since the intensities of TTFields in the body are very low, they do not cause heating. The breakthrough finding made by Novocure was that finely tuned alternating fields of very low intensity, now termed TTFields (Tumor Treating Fields), cause a significant slowing in the growth of cancer cells. Due to the unique geometric shape of cancer cells when they are multiplying, TTFields cause electrically-charged cellular components of these cells to change their location within the dividing cell, disrupting their normal function and ultimately leading to cell death. In addition, cancer cells also contain miniature building blocks which act as tiny motors in moving essential parts of the cells from place to place. TTFields interfere with the normal orientation of these tiny motors related to other cellular components since they are electrically-charged as well. As a result of these two effects, tumor cell division is slowed, results in cellular death or reverses after continuous exposure to TTFields. Other cells in the body (normal healthy tissues) are affected much less than cancer cells since they multiply at a much slower rate if at all. In addition TTFields can be directed to a certain part of the body, leaving sensitive areas out of their reach. Finally, the frequency of TTFields applied to each type of cancer is specific and may not damage normally dividing cells in healthy tissues. In conclusion, TTFields hold the promise of serving as a brand new treatment for pancreatic adenocarcinoma with very few side effects.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 556
• Est. completion date: October 30, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 18 years of age and older

2. Life expectancy of = 3 months

3. Histological/cytological diagnosis of de novo adenocarcinoma of the pancreas

4. Unresectable, locally advanced stage disease according to the following criteria:

• Head/uncinate process:

1. Solid tumor contact with SMA>180°

2. Solid tumor contact with the CA>180°

3. Solid tumor contact with the first jejunal SMA branch

4. Unreconstructible SMV/PV due to tumor involvement or occlusion (can be d/t tumor or bland thrombus)

5. Contact with most proximal draining jejunal branch into SMV

• Body and tail

1. Solid tumor contact of >180° with the SMA or CA

2. Solid tumor contact with the CA and aortic involvement

3. Unreconstructible SMV/PV due to tumor involvement or occlusion (can be d/t tumor or bland thrombus)

• No distant metastasis, including non-regional lymph node metastasis
• No borderline resectable (per Al-Hawary MM, et al., Radiology 201414)

5. ECOG score 0-2

6. Amenable and assigned by the investigator to receive therapy with gemcitabine and nab-paclitaxel

7. Able to operate the NovoTTF-200T System independently or with the help of a caregiver

8. Signed informed consent form for the study protocol

Exclusion Criteria:

1. Prior palliative treatment (e.g. surgery, radiation) to the tumor

2. Cancer requiring anti-tumor treatment within the 5 years before inclusion, excluding treated stage I prostate cancer, in situ cervical or uterus cancer, in situ breast cancer and non-melanomatous skin cancer.

3. Serious co-morbidities:

1. Clinically significant (as determined by the investigator) hematological, hepatic and renal dysfunction, defined as: Neutrophil count < 1.5 x 10^9/L and platelet count < 100 x 10^9/L; bilirubin > 1.5 x Upper Limit of Normal (ULN); AST and/or ALT > 2.5 x ULN; and serum creatinine > 1.5 x ULN.

2. History of significant cardiovascular disease unless the disease is well controlled. Significant cardiac disease includes second/third degree heart block; significant ischemic heart disease; poorly controlled hypertension; congestive heart failure of the New York Heart Association (NYHA) Class II or worse (slight limitation of physical activity; comfortable at rest, but ordinary activity results in fatigue, palpitation or dyspnea).

3. History of arrhythmia that is symptomatic or requires treatment. Patients with atrial fibrillation or flutter controlled by medication are not excluded from participation in the trial.

4. History of cerebrovascular accident (CVA) within 6 months prior to randomization or that is not stable.

5. Active infection or serious underlying medical condition that would impair the ability of the patient to receive protocol therapy.

6. History of any psychiatric condition that might impair patient's ability to understand or comply with the requirements of the study or to provide consent.

4. Concurrent anti-tumor therapy beyond gemcitabine and nab-paclitaxel

5. Implantable electronic medical devices in the torso, such as pacemakers

6. Known severe hypersensitivities to medical adhesives or hydrogel, or to one of the chemotherapies used in this trial.

7. Pregnancy or breast-feeding (female patients with reproductive potential and their partners must accept to use effective contraception throughout the entire study period and for 3 months after the end of treatment). All patients who are capable of becoming pregnant must take a pregnancy test which is negative within 72 hours before beginning treatment. The definition of effective contraception is left up to the decision of the investigator.

8. Unable to follow the protocol for medical, psychological, familial, geographic or other reasons.

9. Admitted to an institution by administrative or court order.

Related Conditions & MeSH terms

• Adenocarcinoma
• Pancreas Adenocarcinoma

Intervention

Device:
• NovoTTF-200T
Patients receive continuous TTFields treatment using the NovoTTF-200T device. TTFields treatment will consist of wearing four electrically insulated electrode arrays on the torso. The treatment enables the patient to maintain regular daily routine.

Drug:
• Gemcitabine
Gemcitabine 1000 mg/m^2 over 30 minute infusion will be administered immediately after nab-paclitaxel on Days 1, 8 and 15 of each 28-day cycle.
• nab paclitaxel
nab-paclitaxel 125 mg/m^2 administered as an intravenous infusion over 30-40 minutes on Days 1, 8 and 15 of each 28-day cycle.

Locations

Country	Name	City	State
Australia	Monash Medical Centre	Clayton
Australia	Greenslopes Private Hospital	Greenslopes	Queensland
Australia	St. John of God Murdoch Hospital	Murdoch	Western Australia
Australia	Sydney Adventist Hospital	Wahroonga
Australia	Westmead Hosptial	Westmead
Austria	Medical University Graz	Graz
Austria	Klinikum Klagenfurt am Wörthersee	Klagenfurt	Wörthersee
Austria	Univ. Klinik für Innere Medizin III der PMU	Salzburg
Austria	Landes-Krankenhaus Steyr	Steyr
Belgium	Faculté de Médecine Campus Erasme	Anderlecht
Belgium	UZ Leuven	Leuven
Belgium	Clinique Universutaire Saint Luc - Institut Roi Albert II	Woluwe-Saint-Lambert
Brazil	Centro de Pesquisa Clínica e Ensino Florianópolis LTDA	Florianópolis
Brazil	Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda	Ijuí
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre
Brazil	Hospital São Lucas da PUCRS	Porto Alegre
Brazil	Irmandade da Santa Casa de Misericórdia de Porto Alegre	Porto Alegre
Brazil	IRPCc - Instituto Ribeirãopretano de Combate ao Câncer	Ribeirão Preto
Brazil	Groupo Clinicas Oncologicas Integradas (COI) - Barra da Tijuca	Rio De Janeiro
Brazil	Instituto D'Or de Pesquisa e Ensino - Rio De Janeiro	Rio De Janeiro
Brazil	Oncoclinicas Group Botafogo	Rio De Janeiro
Brazil	Hospital São Rafael	São Marcos
Brazil	Instituto D´Or de Pesquisa e Ensino - Hospital São Rafael	São Marcos
Brazil	Clínica OncoStar - REDE D´OR	São Paulo
Brazil	Núcleo de Pesquisa Clínica da Rede São Camilo	São Paulo
Brazil	Onco Star SP Oncologia LTDA	São Paulo
Canada	London Regional Cancer Program, London Health Sciences Centre	London	Ontario
Canada	Centre Hospitalier de I'Universitaire de de Montreal (CHUM)	Montréal	Quebec
Canada	Centre Hospitalier Universitaire de Sherbrooke CIUSSS de l'Estrie - CHUS	Sherbrooke	Quebec
China	Beijing Cancer Hospital	Beijing
China	Peking University People'S Hospital	Beijing
China	The first hospital of Jilin University	Changchun
China	Guangdong provincial people's hospital	Guangzhou
China	Sun Yat-sen Memorial Hospital Sun Yat-sen University	Guangzhou	Guangdong
China	Sir Run Run Shaw Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Jilin Guowen Hospital	Jilin
China	Linyi Cancer Hospital	Linyi	Shandong
China	Shanghai Changhai Hospital	Shanghai
China	Shanxi Provincial Cancer Hospital	Shanxi
China	Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology	Wuhan	Hubei
China	Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology	Wuhan	Hubei
China	The First Affiliated Hospital of Xi 'an Jiaotong University	Xi'an	Shaanxi
China	Xingtai People's Hospital	Xingtai
China	Henan Provincial Peoples Hospital	Zhengzhou
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou
Croatia	University Hospital Centre Zagreb	Zagreb
Czechia	Masaryk Institute of Oncology	Brno Stred
Czechia	Nemocnice Nový Jicín	Nový Jicín
Czechia	University Hospital Olomouc	Olomouc
Czechia	General University Hospital in Prague	Praha 2
Czechia	Nemocnice Na Bulovce	Praha 8
France	Institut de Cancérologie de l'Ouest	Angers cedex
France	Centre Hospitalier de Bretagne Sud /Site du Scorff	Lorient
France	Centre Léon Bérard	Lyon
France	Service d'Oncologie médicale du Pr. Andre, Hôpital Saint-Antoine	Paris
France	Hopital haut-Léveque CHU Bordeaux - Service d'Hépato- Gastroentérologie et d'Oncologie digestive	Pessac	Bordeaux
France	Ho^pital Prive´ des Co^tes d'Armor	Plérin
France	Centre de Lutte Contre le Cancer (CLCC) - Centre Paul Strauss	Strasbourg
France	Clinique Sainte Anne - Groupe Hospitalier Saint-Vincent, Strasbourg Oncologie Libérale	Strasbourg
Germany	Klinikum Chemnitz gGmbH	Chemnitz
Germany	Medizinische Hochschule Hannover, Klinik fur Gastroenterologie, Hepatologie und Endokrinologie	Hannover
Germany	VK und K Studien GbR Landshut-Achdorf	Landshut
Germany	Bonifatius Hospital Hematology and Oncology	Lingen
Germany	Carl-von-Basedow-klinikum Saalekrei	Merseburg
Germany	Klinikum München Bogenhausen, Klinik für Gastroenterologie und Gastroenterologische Onkologie	München
Germany	Universitätsklinikum Ulm	Ulm
Hong Kong	Queen Mary Hospital	Hong Kong
Hungary	National Institute of Oncology	Budapest
Hungary	Bekes County Hospital	Gyula
Hungary	Bacs-Kiskun County Hospital	Kecskemét
Hungary	Tolna County Hospital	Szekszárd
Hungary	Jasz-Nagykun-Szolnok County Hospital	Szolnok
Israel	Rambam Health Care Campus, Oncology Institute	Haifa
Israel	Rabin Medical Center	Petah tikva
Israel	Hadassah Medical Center	Ramat Gan
Israel	Sheba Pancreatic Cancer Center - SPCC	Ramat Gan
Israel	Sourasky Medical Center, Oncology Department	Tel Aviv
Italy	A.O. SS Antonio e Biagio e Cesare Arrigo	Alessandria
Italy	Azienda Ospedaliero-Universitaria Careggi	Firenze
Italy	Ospedale San Giovanni Calibita Fatebenefratelli Isola Tiberina	Roma
Italy	Università Campus Bio-Medico di Rome	Roma
Italy	A.O.U Città della Salute e della Scienza di Torino	Torino
Korea, Republic of	Keimyung University, Dongsan hospital	Daegu
Korea, Republic of	National Cancer Center	Gyeonggi-do
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun
Korea, Republic of	Gachon University Gil Hospital	Incheon
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Dong-A University Hospital	Seogu	Busan
Korea, Republic of	CHA Bundang Medical Center, CHA University	Seongnam-si
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Korea, Republic of	Ajou University Hospital	Suwon
Mexico	Centro de Investigación Médica Aguascalientes (CIMA),	Aguascalientes
Mexico	Mediadvance Clinical	Chihuahua	Chih.
Mexico	Clinstile S.A. de C.V.,	Cuauhtémoc
Mexico	Phylasis Clinicas Research S. de R.L. de C.V.	Cuautitlán Izcalli
Mexico	Hospitales Star Medica - Luna Parc	Estado De México
Mexico	Centro de Estudios de Alta Especialidad de Sinaloa, ubicado	Mazatlán	Sinaloa
Mexico	Accelerium S de RL de C.V.	Monterrey	NL
Mexico	Universidad Autonoma de Nuevo Leon - Hospital Universitario "Dr. Jose Eleuterio Gonzalez"	Monterrey
Mexico	Oncocenter - Puebla	Puebla
Mexico	Centro Potosino de Investigación Médica SC,	San Luis Potosí
Mexico	Hospital Angeles San Luis	San Luis Potosí
Mexico	Centro Hemato-Oncologico Privado CHOP	Toluca de Lerdo
Mexico	Phylasis Clinicas Research S.de R.L. de C.V. (PCR)-Toluca	Toluca De Lerdo
Mexico	FAICIC Clinical Research	Veracruz
Poland	Oncology Clinic Clinical Hospital of Przemienienia Panskiego UM in Poznaniu	Poznan
Poland	Centrum Medyczne MrukMed	Rzeszów
Poland	Oncology and Radiotherapy Clinic University Clinical Center Non-Invasive Medicine Center	Warsaw
Poland	Oncology and Radiotherapy Clinic, Oncology Center - Institute	Warsaw
Poland	Jan Mikulicz-Radecki University Teaching Hospital	Wroclaw
Spain	Instituto Oncòlogico Dr. Rosell	Barcelona
Spain	Vall d´Hebron University Hospital	Barcelona
Spain	Hospital General Universitario de Elche	Elche
Spain	HM Hospitales - Centro Integral Oncologico Clara Campal - CIOCC	Madrid
Spain	Hospital Regional Universitario de Málaga	Málaga
Spain	Clinica Universiatria de Navarra	Pamplona
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Spain	Instituto Valenciano de Oncología IVO	Valencia
Switzerland	Hôpital Fribourgeois/Freiburger Spital	Fribourg
Switzerland	KS Winterthur	Winterthur
United States	Pacific Cancer Medical Center	Anaheim	California
United States	Illinois Cancer Specialist - US Oncology Research	Arlington Heights	Illinois
United States	Piedmont Cancer Institute	Atlanta	Georgia
United States	University of Maryland Comprehensive Cancer Center	Baltimore	Maryland
United States	Texas Oncology - Beaumont Mamie McFaddin Ward Cancer Center - US Oncology Research	Beaumont	Texas
United States	Texas Oncology - Bedford - US Oncology Reasearch	Bedford	Texas
United States	Grandview Medical Center, Cancer Center	Birmingham	Alabama
United States	Boca Raton Regional Hospital, Lynn Cancer Institute	Boca Raton	Florida
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Kaleida Health	Buffalo	New York
United States	Gabrail Cancer Research Center	Canton	Ohio
United States	UT/Erlanger Oncology & Hematology	Chattanooga	Tennessee
United States	Rush University Medical Center	Chicago	Illinois
United States	Maryland Oncology Hematology, P.A - US Oncology Research	Columbia	Maryland
United States	Bassett Medical Center	Cooperstown	New York
United States	Methodist Regional Cancer Center	Dallas	Texas
United States	Texas Oncology - Baylor - US Oncology Research	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Astera Cancer Care	East Brunswick	New Jersey
United States	Saint Elizabeth Healthcare	Edgewood	Kentucky
United States	Texas Oncology - El Paso Cancer Treatment Center Gateway - US Oncology Research	El Paso	Texas
United States	Willamette Valley Cancer Institute and Research Center - US Oncology Research	Eugene	Oregon
United States	NorthShore University HealthSystem	Evanston	Illinois
United States	University of Kansas Medical Cancer Center	Fairway	Kansas
United States	New York Hospital Queens	Flushing	New York
United States	Florida Cancer Specialists & Research Institute - Colonial Office	Fort Myers	Florida
United States	Vita Medical Associates, P.C.	Fountain Hill	Pennsylvania
United States	St. Joseph Heritage Healthcare - Virginia K. Crosson Cancer Center	Fullerton	California
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Cancer and Hematology Centers of Western Michigan, PC	Grand Rapids	Michigan
United States	Houston Methodist Cancer Center	Houston	Texas
United States	Mayo Clinic Hospital - Florida	Jacksonville	Florida
United States	MidAmerica Division	Kansas City	Missouri
United States	Tennessee Cancer Specialists	Knoxville	Tennessee
United States	NYU Langone Arena Oncology	Lake Success	New York
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	OptumCare Cancer Care	Las Vegas	Nevada
United States	Central Maine Medical Center, Clinical Research Department	Lewiston	Maine
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Norton Cancer Institute, Norton Healthcare Pavilion	Louisville	Kentucky
United States	Loyola University Medical Center	Maywood	Illinois
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Associated Neurologists of Southern Connecticut, P.C.	Milford	Connecticut
United States	University of Minnesota	Minneapolis	Minnesota
United States	Infirmary Cancer Care	Mobile	Alabama
United States	West Virginia University Cancer Institute	Morgantown	West Virginia
United States	Tennessee Oncology	Nashville	Tennessee
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Vista Oncology Inc PS	Olympia	Washington
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	AdventHealth Neuro Oncology	Orlando	Florida
United States	BRCR Medical Center INC	Plantation	Florida
United States	Renown Institute for Heart & Vascular Health	Reno	Nevada
United States	Oncology and Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care - US Oncology Research	Roanoke	Virginia
United States	Dignity Health - Mercy Cancer Centers	Sacramento	California
United States	Sutter Cancer Center Sacramento	Sacramento	California
United States	Adventist Health St. Helena - Martin-O'Neil Cancer Center (MOCC)	Saint Helena	California
United States	Florida Cancer Specialists	Saint Petersburg	Florida
United States	Ridley-Tree Cancer Center	Santa Barbara	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Florida Hospital Tampa	Tampa	Florida
United States	Baylor Scott and White Medical Center	Temple	Texas
United States	Toledo Clinic Cancer Centers	Toledo	Ohio
United States	Cotton O'Neil Cancer Center (Stormont-Vail Cancer Center)	Topeka	Kansas
United States	Arizona Oncology Associates, PC- HOPE - US Oncology Research	Tucson	Arizona
United States	University of Arizona Cancer Center	Tucson	Arizona
United States	Texas Oncology - Tyler - US Oncology Research	Tyler	Texas
United States	White Plains Hospital - Center for Cancer Care	White Plains	New York
United States	Novant Health Oncology Specialists	Winston-Salem	North Carolina
United States	UMass Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
NovoCure Ltd.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  China,  Croatia,  Czechia,  France,  Germany,  Hong Kong,  Hungary,  Israel,  Italy,  Korea, Republic of,  Mexico,  Poland,  Spain,  Switzerland, 

References & Publications (8)

Giladi M, Schneiderman RS, Porat Y, Munster M, Itzhaki A, Mordechovich D, Cahal S, Kirson ED, Weinberg U, Palti Y. Mitotic disruption and reduced clonogenicity of pancreatic cancer cells in vitro and in vivo by tumor treating fields. Pancreatology. 2014 Jan-Feb;14(1):54-63. doi: 10.1016/j.pan.2013.11.009. Epub 2013 Dec 4. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: JAMA. 2018 May 1;319(17):1824. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival		4 years
Secondary	Progression-free survival		4 years
Secondary	Local progression-free survival		4 years
Secondary	Objective response rate		4 years
Secondary	One-year survival rate		4 years
Secondary	Quality of life	Quality of life will be assessed using the EORTC QLQ C-30 questionnaire with EORTC QLQ-PAN26 (Pancreatic Cancer symptom) supplement.	4 years
Secondary	Pain-free survival	Pain-free survival will measured as the duration between the time of randomization until a greater than or equal to two-point decline from a baseline measurement in a patient self-reported visual analogue scale (VAS) is recorded or death, whichever occurs first.	4 years
Secondary	Puncture-free survival		4 years
Secondary	Resectability rate		4 years
Secondary	Toxicity profile	Toxicity profile in patients treated with TTFields in combination with gemcitabine and nab-paclitaxel compared to the toxicity profile of patients treated with chemotherapy alone, measured by the rate of treatment-emergent toxicities in both arms. Adverse events will be collected and recorded based on the revised Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.	4 years