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)

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

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.

Study Overview

• Status: Completed
• Conditions: Pancreas Adenocarcinoma
• Intervention / Treatment: Drug: Gemcitabine; Drug: nab paclitaxel; Device: NovoTTF-200T

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 571
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Clayton, Australia, VIC 3168
    • Monash Medical Centre
  • Wahroonga, Australia, NSW 2076
    • Sydney Adventist Hospital
  • Westmead, Australia, NSW 2145
    • Westmead Hosptial
  • Queensland
    • Greenslopes, Queensland, Australia, 4120
      • Greenslopes Private Hospital
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • St. John of God Murdoch Hospital
• Austria
  • Graz, Austria, 17070
    • Medical University Graz
  • Salzburg, Austria, 5020
    • Univ. Klinik für Innere Medizin III der PMU
  • Steyr, Austria, 4400
    • Landes-Krankenhaus Steyr
  • Wörthersee
    • Klagenfurt, Wörthersee, Austria, 9020
      • Klinikum Klagenfurt am Wörthersee
• Belgium
  • Anderlecht, Belgium, 1070
    • Faculté de Médecine Campus Erasme
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Woluwe-Saint-Lambert, Belgium, 1200
    • Clinique Universutaire Saint Luc - Institut Roi Albert II
• Brazil
  • Florianópolis, Brazil, 88020
    • Centro de Pesquisa Clínica e Ensino Florianópolis LTDA
  • Ijuí, Brazil, 98700
    • Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda
  • Porto Alegre, Brazil, 90020-090
    • Irmandade da Santa Casa de Misericordia de Porto Alegre
  • Porto Alegre, Brazil, 90035
    • Hospital de Clinicas de Porto Alegre
  • Porto Alegre, Brazil, 90610
    • Hospital Sao Lucas Da Pucrs
  • Ribeirão Preto, Brazil, 14015-130
    • IRPCc - Instituto Ribeirãopretano de Combate ao Câncer
  • Rio de Janeiro, Brazil, 22250-040
    • Oncoclinicas Group Botafogo
  • Rio de Janeiro, Brazil, 22271
    • Instituto D'Or de Pesquisa e Ensino - Rio de Janeiro
  • Rio de Janeiro, Brazil, 22775-001
    • Groupo Clinicas Oncologicas Integradas (COI) - Barra da Tijuca
  • São Marcos, Brazil, 41253-190
    • Instituto D´Or de Pesquisa e Ensino - Hospital São Rafael
  • São Paulo, Brazil, 04014-002
    • Núcleo de Pesquisa Clínica da Rede São Camilo
  • São Paulo, Brazil, 04543
    • Clínica OncoStar - REDE D´OR
• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Regional Cancer Program, London Health Sciences Centre
  • Quebec
    • Montreal, Quebec, Canada, H2X 3E4
      • Centre Hospitalier de I'Universitaire de de Montreal (CHUM)
    • Sherbrooke, Quebec, Canada, J1G 1B1
      • Centre Hospitalier Universitaire de Sherbrooke CIUSSS de l'Estrie - CHUS
• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Beijing, China
    • Peking Union Medical College Hospital
  • Beijing, China
    • Peking University People's Hospital
  • Changchun, China, 130021
    • The First Hospital of Jilin University
  • Guangzhou, China, 510000
    • Guangdong Provincial People's Hospital
  • Jilin, China, 136100
    • Jilin Guowen Hospital
  • Shanghai, China, 200433
    • Shanghai Changhai Hospital
  • Shanxi, China, 030013
    • Shanxi Provincial Cancer Hospital
  • Xingtai, China
    • Xingtai People's Hospital
  • Zhengzhou, China, 450052
    • the First Affiliated Hospital of Zhengzhou University
  • Zhengzhou, China
    • Henan Provincial Peoples Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Sun Yat-sen Memorial Hospital Sun Yat-sen University
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150086
      • Harbin Medical University Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430014
      • Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • The First Affiliated Hospital of Xi 'An Jiaotong University
  • Shandong
    • Linyi, Shandong, China, 276000
      • LinYi Cancer Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
• Croatia
  • Zagreb, Croatia, 10000
    • University Hospital Centre Zagreb
• Czechia
  • Brno střed, Czechia, 60200
    • Masaryk Institute of Oncology
  • Nový Jičín, Czechia, 741 01
    • Nemocnice Novy Jicin
  • Olomouc, Czechia, 779 00
    • University Hospital Olomouc
  • Prague, Czechia, 128 08
    • General University Hospital in Prague
  • Prague, Czechia, 180 81
    • Nemocnice Na Bulovce
• France
  • Lorient, France, 56322
    • Centre Hospitalier de Bretagne Sud /Site du Scorff
  • Lyon, France
    • Centre Leon Berard
  • Paris, France, 75012
    • Service d'Oncologie médicale du Pr. Andre, Hôpital Saint-Antoine
  • Plérin, France, 22190
    • Hôpital privé des Côtes d'Armor
  • Saint-Herblain, France, 44805
    • Institut de Cancérologie de l'Ouest
  • Strasbourg, France, 67000
    • Centre de Lutte Contre le Cancer (CLCC) - Centre Paul Strauss
  • Strasbourg, France, 67000
    • Clinique Sainte Anne - Groupe Hospitalier Saint-Vincent, Strasbourg Oncologie Libérale
  • Bordeaux
    • Pessac, Bordeaux, France, 33604
      • Hopital haut-Léveque CHU Bordeaux - Service d'Hépato- Gastroentérologie et d'Oncologie digestive
• Germany
  • Chemnitz, Germany, 09116
    • Klinikum Chemnitz gGmbH
  • Hanover, Germany
    • Medizinische Hochschule Hannover, Klinik fur Gastroenterologie, Hepatologie und Endokrinologie
  • Landshut, Germany, 84036
    • VK und K Studien GbR Landshut-Achdorf
  • Lingen, Germany, 49808
    • Bonifatius Hospital Hematology and Oncology
  • Merseburg, Germany, 06217
    • Carl-von-Basedow-klinikum Saalekrei
  • München, Germany, 81925
    • Klinikum München Bogenhausen, Klinik für Gastroenterologie und Gastroenterologische Onkologie
  • Ulm, Germany, D-89081
    • Universitatsklinikum Ulm
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
• Hungary
  • Budapest, Hungary, 1122
    • National Institute of Oncology
  • Gyula, Hungary, 5700
    • Békés county hospital
  • Kecskemét, Hungary, 6000
    • Bacs-Kiskun County Hospital
  • Szekszárd, Hungary, 7100
    • Tolna County Hospital
  • Szolnok, Hungary, 5000
    • Jasz-Nagykun-Szolnok County Hospital
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus, Oncology Institute
  • Jerusalem, Israel, 9112000
    • Hadassah Medical Center
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center
  • Ramat Gan, Israel
    • Sheba Pancreatic Cancer Center - SPCC
  • Tel Aviv, Israel, 64239
    • Sourasky Medical Center, Oncology Department
• Italy
  • Alessandria, Italy, 15121
    • A.O. SS Antonio e Biagio e Cesare Arrigo
  • Florence, Italy, 50134
    • Azienda Ospedaliero-Universitaria Careggi
  • Roma, Italy, 00128
    • Università Campus Bio-Medico di Rome
  • Roma, Italy, 00186
    • Ospedale San Giovanni Calibita Fatebenefratelli Isola Tiberina
  • Torino, Italy, 10126
    • A.O.U Città della Salute e della Scienza di Torino
• Mexico
  • Aguascalientes, Mexico, 20116
    • Centro de Investigación Médica Aguascalientes (CIMA),
  • Cuauhtémoc, Mexico, 06700
    • Clinstile S.A. de C.V.,
  • Cuautitlán Izcalli, Mexico, 54769
    • Phylasis Clinicas Research S. de R.L. de C.V.
  • Estado de México, Mexico, 54750
    • Hospitales Star Medica - Luna Parc
  • Monterrey, Mexico, 64460
    • Universidad Autonoma de Nuevo Leon - Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
  • Puebla City, Mexico, 72530
    • Oncocenter - Puebla
  • San Luis Potosí City, Mexico, 78200
    • Hospital Angeles San Luis
  • San Luis Potosí City, Mexico, 78250
    • Centro Potosino de Investigación Médica SC,
  • Toluca, Mexico, 50080
    • Centro Hemato-Oncologico Privado CHOP
  • Toluca, Mexico, 50180
    • Phylasis Clinicas Research S.de R.L. de C.V. (PCR)-Toluca
  • Veracruz, Mexico, 91900
    • FAICIC Clínical Research
  • Chih.
    • Chihuahua City, Chih., Mexico, 31210
      • Mediadvance Clinical
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64000
      • Accelerium S de RL de C.V.
  • Sinaloa
    • Mazatlán, Sinaloa, Mexico, 82110
      • Centro de Estudios de Alta Especialidad de Sinaloa, ubicado
• Poland
  • Poznan, Poland, 60-596
    • Oncology Clinic Clinical Hospital of Przemienienia Pańskiego UM in Poznaniu
  • Rzeszów, Poland, 35-021
    • Centrum Medyczne Mrukmed
  • Warsaw, Poland, 02-034
    • Oncology and Radiotherapy Clinic, Oncology Center - Institute
  • Warsaw, Poland, 02-507
    • Oncology and Radiotherapy Clinic University Clinical Center Non-Invasive Medicine Center
  • Wroclaw, Poland, 50-556
    • Jan Mikulicz-Radecki University Teaching Hospital
• South Korea
  • Daegu, South Korea, 42601
    • Keimyung University, Dongsan hospital
  • Gyeonggi-do, South Korea, 10408
    • National Cancer Center
  • Hwasun, South Korea, 58128
    • Chonnam National University Hwasun Hospital
  • Incheon, South Korea, 22332
    • Inha University Hospital
  • Incheon, South Korea, 21565
    • Gachon University Gil Hospital
  • Seongnam-si, South Korea
    • Cha Bundang Medical Center, Cha University
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 06591
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Seoul, South Korea, 08308
    • Korea University Guro Hospital
  • Suwon, South Korea, 16499
    • Ajou University Hospital
  • Busan
    • Seogu, Busan, South Korea, 602-715
      • Dong-A University Hospital
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, South Korea, 13620
      • Seoul National University Bundang Hospital
• Spain
  • Barcelona, Spain, 08028
    • Instituto Oncológico Dr. Rosell
  • Barcelona, Spain
    • Vall d´Hebron University Hospital
  • Elche, Spain
    • Hospital General Universitario de Elche
  • Madrid, Spain, 28050
    • HM Hospitales - Centro Integral Oncologico Clara Campal - CIOCC
  • Madrid, Spain
    • Hospital Universitario Ramon Y Cajal Carretera de Colmenar Viejo
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Málaga
  • Pamplona, Spain, 31008
    • Clinica Universiatria de Navarra
  • Santander, Spain
    • Hospital Universitario Marques de Valdecilla
  • Valencia, Spain, 46009
    • Instituto Valenciano de Oncologia IVO
• Switzerland
  • Fribourg, Switzerland, 1708
    • Hôpital Fribourgeois/Freiburger Spital
  • Winterthur, Switzerland, 8401
    • KS Winterthur
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35243
      • Grandview Medical Center, Cancer Center
    • Mobile, Alabama, United States, 36607
      • Infirmary Cancer Care
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Tucson, Arizona, United States, 85724-5024
      • University of Arizona Cancer Center
    • Tucson, Arizona, United States, 85711
      • Arizona Oncology Associates, PC- HOPE - US Oncology Research
  • California
    • Anaheim, California, United States, 92801
      • Pacific Cancer Medical Center
    • Fullerton, California, United States, 92835
      • Providence Medical Foundation
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Sacramento, California, United States, 95816
      • Dignity Health - Mercy Cancer Centers
    • Sacramento, California, United States, 95816
      • Sutter Cancer Center Sacramento
    • Santa Barbara, California, United States, 93105
      • Ridley-Tree Cancer Center
    • St. Helena, California, United States, 94574
      • Adventist Health St. Helena - Martin-O'Neil Cancer Center (MOCC)
  • Connecticut
    • Milford, Connecticut, United States, 06460
      • Associated Neurologists of Southern Connecticut, P.C.
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Boca Raton Regional Hospital, Lynn Cancer Institute
    • Fleming Island, Florida, United States, 32003
      • Cancer Specialist of North Florida
    • Fort Myers, Florida, United States, 33905
      • Florida Cancer Specialists & Research Institute - Colonial Office
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Hospital - Florida
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center
    • Orlando, Florida, United States, 32804
      • AdventHealth Neuro Oncology
    • Plantation, Florida, United States, 33324
      • BRCR Medical Center Inc
    • St. Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists
    • Tampa, Florida, United States, 33613
      • Florida Hospital Tampa
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Piedmont Cancer Institute
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Illinois Cancer Specialist - US Oncology Research
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Evanston, Illinois, United States, 60201
      • Northshore University Healthsystem
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Medical Cancer Center
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Cancer Center (Stormont-Vail Cancer Center)
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • Saint Elizabeth Healthcare
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute, Norton Healthcare Pavilion
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center
  • Maine
    • Lewiston, Maine, United States, 04240
      • Central Maine Medical Center, Clinical Research Department
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Comprehensive Cancer Center
    • Columbia, Maryland, United States, 21044
      • Maryland Oncology Hematology, P.A - US Oncology Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Worcester, Massachusetts, United States, 01605
      • UMass Memorial Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
    • Grand Rapids, Michigan, United States, 49503
      • Cancer and Hematology Centers of Western Michigan, PC
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • MidAmerica Division
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • OptumCare Cancer Care
    • Las Vegas, Nevada, United States, 89619
      • Comprehensive Cancer Centers of Nevada
    • Reno, Nevada, United States, 89502
      • Renown Regional Medical Center & Renown Institute for Cancer
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • Astera Cancer Care
  • New York
    • Buffalo, New York, United States, 14210
      • Kaleida Health
    • Cooperstown, New York, United States, 13326
      • Bassett Medical Center
    • Flushing, New York, United States, 11355
      • New York Hospital Queens
    • Lake Success, New York, United States, 11042
      • NYU Langone Arena Oncology
    • White Plains, New York, United States, 10601
      • White Plains Hospital - Center for Cancer Care
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Novant Health Oncology Specialists
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Research Center
    • Toledo, Ohio, United States, 44614
      • Toledo Clinic Cancer Centers
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Willamette Valley Cancer Institute and Research Center - US Oncology Research
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Fountain Hill, Pennsylvania, United States, 18015
      • Vita Medical Associates, P.C.
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • UT/Erlanger Oncology & Hematology
    • Knoxville, Tennessee, United States, 37909-1327
      • Tennessee Cancer Specialists
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology
  • Texas
    • Beaumont, Texas, United States, 77702
      • Texas Oncology - Beaumont Mamie McFaddin Ward Cancer Center - US Oncology Research
    • Bedford, Texas, United States, 76022
      • Texas Oncology - Bedford - US Oncology Reasearch
    • Dallas, Texas, United States, 75203
      • Methodist Regional Cancer Center
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Baylor - US Oncology Research
    • El Paso, Texas, United States, 79915
      • Texas Oncology - El Paso Cancer Treatment Center Gateway - US Oncology Research
    • Houston, Texas, United States, 77030
      • Houston Methodist Cancer Center
    • Temple, Texas, United States, 76508
      • Baylor Scott and White Medical Center
    • Tyler, Texas, United States, 75702
      • Texas Oncology - Tyler - US Oncology Research
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • Oncology and Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care - US Oncology Research
  • Washington
    • Olympia, Washington, United States, 98506
      • Vista Oncology Inc PS
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Best Standard of Care; Patients receive best standard of care with gemcitabine and nab-Paclitaxel	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.; Drug: 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.
Experimental: NovoTTF-200T; Patients receive TTFields using the NovoTTF-200T System together with gemcitabine and nab-Paclitaxel	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.; Drug: 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.; 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.; Other Names: TTFields

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival of Subjects Treated With TTFields Concomitant With Gemcitabine and Nab-paclitaxel vs Chemotherapy Alone	Overall survival of subjects treated with TTFields concomitant with gemcitabine and nab-paclitaxel in the first line treatment of unresectable, locally advanced pancreatic cancer subjects, compared to overall survival of subjects treated with chemotherapy alone, measured as the period between the time of randomization and the time of death.	From randomization until death from any cause or last known alive.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival of Subjects Treated With TTFields Concomitant With Gemcitabine and Nab-paclitaxel vs Chemotherapy Alone	Progression-free survival of subjects treated with TTFields concomitant with gemcitabine and nab-paclitaxel in the first line treatment of unresectable, locally advanced pancreatic cancer subjects, compared to the progression-free survival of subjects treated with chemotherapy alone, measured from the time of randomization and based on CT scans collected on the study, using the revised RECIST V1.1 Criteria. Progression is defined using the RECIST 1.1 criteria: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, in addition the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, progression was defined as unequivocal progression (an overall level of substantial worsening in non-target disease) of existing non-target lesions. The appearance of one or more new lesions is also considered progression.	From randomization until radiologic disease progression per RECIST v1.1 or death, whichever occurs first.
Local Progression-free Survival of Subjects Treated With TTFields Concomitant With Gemcitabine and Nab-paclitaxel vs Chemotherapy Alone	Local progression-free survival of subjects treated with TTFields concomitant with gemcitabine and nab-paclitaxel in the first line treatment of unresectable, locally advanced pancreatic cancer subjects, compared to the local progression-free survival of subjects treated with chemotherapy alone, measured from the time of randomization and based on CT scans collected on the study, using the revised RECIST V1.1 Criteria. Local progression is defined per RECIST 1.1 in the absence of distant metastasis: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, in addition the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, progression was defined as unequivocal progression (an overall level of substantial worsening) of existing non-target lesions. The appearance of one or more new lesions is also considered progression.	From randomization until local disease progression per RECIST v1.1 (in the absence of distant metastasis) or death, whichever occurs first.
Objective Response Rate of Subjects Treated With TTFields Concomitant With Gemcitabine and Nab-paclitaxel vs Chemotherapy Alone	Objective Response Rate (ORR) was assessed per RECIST v1.1. Complete Response (CR): disappearance of all target and non-target lesions and reduction of pathological lymph nodes to <10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions from baseline without new lesions or progression of non-target lesions. ORR is defined as the percentage of participants whose best overall response was CR or PR.	From randomization until radiologic disease progression per RECIST v1.1 or end of tumor assessment follow-up.
One-year Survival Rate of Subjects Treated With TTFields Concomitant With Gemcitabine and Nab-paclitaxel vs Chemotherapy Alone	One-year survival rate of subjects treated with TTFields concomitant with gemcitabine and nab-paclitaxel in the first line treatment of unresectable, locally advanced pancreatic cancer subjects, compared to the 1-year survival rate of subjects treated with chemotherapy alone.	From randomization through 12 months after randomization.
Quality of Life of Subjects Treated With TTFields Concomitant With Gemcitabine and Nab-paclitaxel vs Chemotherapy Alone	Quality of life deterioration-free survival (DFS) was assessed using the EORTC QLQ-C30 and pancreatic cancer-specific QLQ-PAN26 questionnaires. Higher scores on functional and global health status scales indicate better functioning, whereas higher symptom scores indicate worse symptoms. DFS was defined as the time from randomization to the first ≥10-point deterioration from baseline without a subsequent ≥10-point improvement, or death. DFS was evaluated separately for each QoL domain included in the analysis.	From randomization until the first ≥10-point deterioration without subsequent improvement, or death, assessed for the duration of study follow-up.
Pain-free Survival of Subjects Treated With TTFields Concomitant With Gemcitabine and Nab-paclitaxel vs Chemotherapy Alone	Pain-free survival was measured as the duration between the time of randomization until a greater than or equal to twenty-point increase from baseline in a patient self-reported visual analogue scale (VAS) was recorded or death, whichever occurred first.	From randomization until a ≥20-point increase from baseline in pain on the patient-reported visual analogue scale (0-100) or death, whichever occurs first.
Puncture-free Survival of Subjects Treated With TTFields Concomitant With Gemcitabine and Nab-paclitaxel vs Chemotherapy Alone	Puncture-free survival of subjects treated with TTFields concomitant with gemcitabine and nab-paclitaxel in the first line treatment of unresectable, locally advanced pancreatic cancer subjects, compared to puncture-free survival of subjects treated with chemotherapy alone, measured as the duration between randomization until the first need for paracentesis or death, whichever occurs first.	From randomization until the first paracentesis or death, whichever occurs first.
Resectability Rate of Subjects Treated With TTFields Concomitant With Gemcitabine and Nab-paclitaxel vs Chemotherapy Alone	Resectability rate defined as the number and percentage of patients whose tumors were deemed resectable and who underwent surgery.	From randomization through the end of study follow-up. Surgical resections were captured throughout study follow-up, up to approximately 18 months.

Collaborators and Investigators

• Sponsor: NovoCure Ltd.

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Babiker HM, Picozzi V, Chandana SR, Melichar B, Kasi A, Gang J, Gallego J, Bullock A, Chunyi H, Wyrwicz L, Hitre E, Osipov A, de la Fouchardiere C, Ales I, Dragovich T, Lee W, Feeney K, Philip P, Ueno M, Van Cutsem E, Seufferlein T, Macarulla T; PANOVA-3 Study Investigators. Tumor Treating Fields With Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: Randomized, Open-Label, Pivotal Phase III PANOVA-3 Study. J Clin Oncol. 2025 Jul 20;43(21):2350-2360. doi: 10.1200/JCO-25-00746. Epub 2025 May 31.

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2018
• Primary Completion (Actual): October 16, 2024
• Study Completion (Actual): October 16, 2024

Study Registration Dates

• First Submitted: December 6, 2017
• First Submitted That Met QC Criteria: December 18, 2017
• First Posted (Actual): December 19, 2017

Study Record Updates

• Last Update Posted (Actual): January 21, 2026
• Last Update Submitted That Met QC Criteria: January 1, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Gemcitabine; TTFields; Tumor Treating Fields; TTF; Locally Advanced Pancreatic Adenocarcinoma; nab-Paclitaxel; Minimal toxicity; Novocure
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Adenocarcinoma; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Health Care Economics and Organizations; Economics; Gemcitabine; Taxes
• Other Study ID Numbers: EF-27

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes