Effect of Tumor Treating Fields (TTFields, 200 kHz) Concomitant With Weekly Paclitaxel for the Treatment of Recurrent Ovarian Cancer (ENGOT-ov50 / GOG-3029 / INNOVATE-3)
- Registration Number
- NCT03940196
- Lead Sponsor
- NovoCure Ltd.
- Brief Summary
The study is a prospective, randomized controlled phase III trial aimed to test the efficacy and safety of Tumor Treating Fields (TTFields) concomitant with weekly paclitaxel for the treatment of recurrent ovarian cancer . 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.
- 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 ovarian carcinoma 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. In addition, TTFields have shown to inhibit metastatic spread of malignant melanoma in in vivo experiment.
In a pilot study, 31 patients with recurrent platinum-resistant ovarian carcinoma received paclitaxel together with TTFields (200 kHz) applied to the abdomen/pelvis 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). 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.
DESCRIPTION OF THE TRIAL:
All patients included in this trial are patients with platinum-resistant ovarian carcinoma. In addition, all patients must meet all eligibility criteria.
Eligible patients will be randomly assigned to one of two groups:
1. Patients receive TTFields at 200 kHz to the abdomen and pelvis using the NovoTTF-100L(O) System together with weekly paclitaxel.
2. Patients receive weekly paclitaxel alone.
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-100L(O) group, the patients will be treated continuously with the device until progression in the abdomen/pelvis. On both arms, patients who have progression outside the abdomen/pelvis 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 (200 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 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 could potentially become treatment for ovarian cancer with very few side effects.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 540
- 18 years of age and older
- Epithelial histology of ovarian/primary peritoneal or fallopian tube carcinoma at the time of diagnosis
- Life expectancy of ≥ 12 weeks
- Maximum two prior lines of systemic therapy following diagnosis of platinum-resistance
- Maximum total of 5 prior lines of systemic therapy
- Amenable to receive weekly paclitaxel and able to operate the NovoTTF-100L(O) System
- ECOG 0-1
- Evaluable (measurable or non-measurable) disease in the abdominal/pelvic region per RECIST V1.
- Signed informed consent form for the study protocol
- Primary platinum-refractory disease (progression per RECIST V1.1 during or within 1 month after first line therapy), while secondary platinum-refractory disease is allowed
- Prior disease progression on a weekly paclitaxel for recurrent disease
- Brain metastasis or leptomeningeal spread of the tumor
- Albumin level <25 gram/liter (subjects should not receive total parenteral nutrition or albumin within 2 weeks of the test)
- CTCAE V5.0 Grade 3 or higher peripheral neuropathy
- Implantable electrical medical devices
- Known allergies to medical adhesives or hydrogel
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to paclitaxel or drugs similar or related to paclitaxel, except for cases that were able to undergo desensitization per investigator
- Prior malignancies treated primarily or for recurrence within 2 years prior to inclusion in this study, except for completely resected non-melanomatous skin carcinoma, or successfully treated in situ carcinoma of the skin, breast or cervix of the uterus
- Serious co-morbidities
- Concurrent anti-tumor therapy beyond weekly paclitaxel, excluding hormonal therapy for breast cancer
- Concurrent active treatment in another clinical trial. However prior participation in clinical trials is allowed as well as participation during survival follow-up
- 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
- Admitted to an institution by administrative or court order
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description NovoTTF-100L(O) NovoTTF-100L(O) Patients receive TTFields using the NovoTTF-100L(O) System together with weekly Paclitaxel NovoTTF-100L(O) Paclitaxel Patients receive TTFields using the NovoTTF-100L(O) System together with weekly Paclitaxel Best Standard of Care Paclitaxel Patients receive best standard of care with weekly Paclitaxel
- Primary Outcome Measures
Name Time Method Overall survival 4 years
- Secondary Outcome Measures
Name Time Method Progression-free survival 4 years Quality of life using the EORTC QLQ C30 questionnaire with the ovarian cancer symptom OV28 module. 4 years Objective response rate 4 years Next progression-free survival 4 years Measured from the time of randomization to tumor progression on next-line treatment
Time to first and second subsequent treatment 4 years Measured as the time from the date of randomization to the clinical decision made by the investigator to initiate a first and second subsequent lines of treatment, respectively, or death date
Time to undisputable deterioration in health-related quality of life (HRQoL) 4 years Measured as the time interval between randomization until the first decrease in HRQoL score ≥ 10-point with no further improvement in HRQoL score ≥ 10 points on any further HRQoL data, based on the EORTC QLQ-C30 questionnaire
Severity and frequency of adverse events 4 years
Trial Locations
- Locations (107)
Center of Hope at Renown Medical Center
🇺🇸Reno, Nevada, United States
UPMC Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Minnesota Oncology Hematology, PA
🇺🇸Saint Paul, Minnesota, United States
Hoag Memorial Hospital Presbyterian
🇺🇸Newport Beach, California, United States
Texas Oncology
🇺🇸The Woodlands, Texas, United States
The University of Texas Medical School at Houston
🇺🇸Houston, Texas, United States
Texas Oncology-McAllen
🇺🇸McAllen, Texas, United States
California Pacific Medical Center- Pacific Campus
🇺🇸San Francisco, California, United States
Arizona Oncology- Biltmore Cancer Center
🇺🇸Phoenix, Arizona, United States
Texas Oncology San Antonio Medical Center
🇺🇸San Antonio, Texas, United States
Rocky Mountain Cancer Centers
🇺🇸Thornton, Colorado, United States
IRCCS Ospedale San Raffaele, U.O. Ginecologia-Ematologia e TMO
🇮🇹Milano, Italy
Fondazione Policlinico Universitario Gemelli
🇮🇹Roma, Italy
Arizona Oncology
🇺🇸Tucson, Arizona, United States
Univ.-Klinik für Gynäkologie und Geburtshilfe, Innsbruck
🇦🇹Innsbruck, Austria
ASST Lecco - Ospedale Manzoni, Dipartimento Oncologico
🇮🇹Lecco, Italy
Szpitale Pomorskie Sp. z o.o.
🇵🇱Gdynia, Poland
Methodist Estabrook Cancer Center
🇺🇸Omaha, Nebraska, United States
Broward Health Medical Center
🇺🇸Fort Lauderdale, Florida, United States
Rush University Cancer Center - Chicago and Innovation
🇺🇸Chicago, Illinois, United States
Women's Cancer Center of Nevada
🇺🇸Las Vegas, Nevada, United States
Sanford Gynecologic Oncology Clinic
🇺🇸Sioux Falls, South Dakota, United States
Texas Oncology Austin-Midtown
🇺🇸Austin, Texas, United States
Texas Oncology-Tyler
🇺🇸Tyler, Texas, United States
Oncology Institute, Galilee Medical Center
🇮🇱Nahariya, Israel
University Medical Center Utrech
🇳🇱Utrecht, Netherlands
Oddział Kliniczny Chirurgii Ogólnej i Onkologicznej, Szpital Św. Rafała
🇵🇱Kraków, Poland
Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie, Klinika Ginekologii Operacyjnej i Onkologii Ginekologicznej Dorosłych i Dziewcząt
🇵🇱Szczecin, Poland
Szpital Kliniczny im. ks. Anny Mazowieckiej
🇵🇱Warsaw, Poland
Gynecological Tumor Center, University Hospital Basel
🇨🇭Basel, Switzerland
Hospital MD Anderson Cancer Center
🇪🇸Madrid, Spain
Servicio de Oncología Médica, Hospital Universitario Quirón Dexeus
🇪🇸Barcelona, Spain
Hospital 12 de Octubre. Servicio Oncología Médica
🇪🇸Madrid, Spain
IOSI Bellinzona, Oncology Institute of Southern Switzerland, Ospedale San Giovanni
🇨🇭Bellinzona, Switzerland
Gynekologicko-porodnická klinika, Fakultní nemocnice Královské Vinohrady
🇨🇿Praha 10, Czechia
University of California
🇺🇸La Jolla, California, United States
Olive View - UCLA Medical Center
🇺🇸Sylmar, California, United States
Northeast Georgia Medical Center
🇺🇸Gainesville, Georgia, United States
Des Moines Oncology Research Association
🇺🇸Des Moines, Iowa, United States
Maryland Oncology Hematology, P.A.
🇺🇸Silver Spring, Maryland, United States
Lahey Hospital & Medical Center
🇺🇸Burlington, Massachusetts, United States
Washington University School of Medicine in St. Louis
🇺🇸Saint Louis, Missouri, United States
MD Anderson Cancer Center at Cooper
🇺🇸Camden, New Jersey, United States
The Valley Hospital
🇺🇸Paramus, New Jersey, United States
Miami Valley Hospital South
🇺🇸Centerville, Ohio, United States
The Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
West Penn OB/GYN
🇺🇸Pittsburgh, Pennsylvania, United States
Northwest Cancer Specialists, PC
🇺🇸Portland, Oregon, United States
Abington Hospital- Asplundh Cancer Pavilion
🇺🇸Willow Grove, Pennsylvania, United States
Women & Infants Hospital of Rhode Island
🇺🇸Providence, Rhode Island, United States
Texas Oncology Austin-Balcones
🇺🇸Austin, Texas, United States
Texas Oncology Austin-North Austin
🇺🇸Austin, Texas, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Texas Oncology-Fort Worth
🇺🇸Fort Worth, Texas, United States
Texas Oncology-Deke Slayton Cancer Center
🇺🇸Webster, Texas, United States
Carilion Clinic-Gynecologic Oncology
🇺🇸Roanoke, Virginia, United States
Texas Oncology - Sugar Land
🇺🇸Sugar Land, Texas, United States
Univ.-Klinik für Gynäkologie und Geburtshilfe
🇦🇹Graz, Austria
Multicare Institute for Research and Innovation
🇺🇸Tacoma, Washington, United States
KH der Barmherzigen Brüder Graz
🇦🇹Graz, Austria
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Imelda Ziekenhuis Bonheiden
🇧🇪Bonheiden, Belgium
Landesfrauenklinik Salzburg
🇦🇹Salzburg, Austria
Cliniques Universitaires Saint Luc, Institut Roi Albert II
🇧🇪Brussel, Belgium
Grand Hôpital de Charleroi, Oncologie-Hématologie
🇧🇪Charleroi, Belgium
AZ Maria Middelares, Clinical Trial Unit Medical Oncology - Integrated Cancer Center Ghent
🇧🇪Gent, Belgium
UZ Gent
🇧🇪Gent, Belgium
University Hospitals Leuven, Leuven Cancer Institute
🇧🇪Leuven, Belgium
CHU Ambroise Paré
🇧🇪Mons, Belgium
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
CHU UCL Namur - Site Ste Elisabeth
🇧🇪Namur, Belgium
Centre Hospitalie
🇨🇦Montréal, Quebec, Canada
Tom Baker Cancer Center
🇨🇦Calgary, Canada
Onkologická Klinika Fakultní nemocnice Olomouc
🇨🇿Olomouc, Czechia
Jewish General Hospital
🇨🇦Montréal, Canada
University Hospital Ostrava
🇨🇿Ostrava-Poruba, Czechia
McGill University Health Centre
🇨🇦Montréal, Canada
Gynekologicko-porodnická klinika 1. LF UK a VFN
🇨🇿Praha 2, Czechia
Presidio Ospedaliero Antonio Perrino - ASL Brindisi
🇮🇹Brindisi, Italy
Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Klinik für Gynäkologie
🇩🇪Berlin, Germany
Gynekologicko-porodnické oddělení - Nemocnice České Budějovice a.s.
🇨🇿České Budějovice, Czechia
Universitätsklinikum Carl Gustav Carus
🇩🇪Dresden, Germany
Semmelweis University
🇭🇺Budapest, Hungary
Nőgyógyászati Osztály, Országos Onkológiai Intézet
🇭🇺Budapest, Hungary
Horst-Schmidt-Kliniken, Gynecology and Gynecologic, Oncology Department
🇩🇪Wiesbaden, Germany
Szuleszeti és Nogyogyaszati Klinika
🇭🇺Debrecen, Hungary
Hillel Yaffe Medical Center
🇮🇱Hadera, Israel
Saare Zedek Medical Center - Gyneco-Oncology
🇮🇱Jerusalem, Israel
Policlinico S. Orsola-Malpighi, SSD Oncologia Medica Addarii
🇮🇹Bologna, Italy
Gyneco-Oncology Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Dipartimento Medicina e Chirurgia, Università Milano-Bicocca, Direttore Programma Ginecologia Oncologica, Istituto Europeo Oncologia
🇮🇹Milano, Italy
Istituto Nazionale Tumori IRCCS Fondazione Pascale
🇮🇹Napoli, Italy
University Saint Anna
🇮🇹Torino, Italy
Amsterdam Universitair Medische centra
🇳🇱Amsterdam, Netherlands
Samodzielny Publiczny Zakład Opieki Zdrowotnej MSWiA z Warmińsko-Mazurskim Centrum Onkologii w Olsztynie, Oddział Kliniczny Onkologii i Immunoonkologii z Ośrodkiem Dziennym Terapii Onkologicznej
🇵🇱Olsztyn, Poland
Uniwersytet Medyczny w Lublinie, I Klinika Ginekologii Onkologicznej i Ginekologii
🇵🇱Lublin, Poland
Oddział Ginekologii Onkologicznej Katedry i Kliniki Onkologii Uniwersytetu Medycznego w Poznaniu
🇵🇱Poznań, Poland
lnstitut Catala d'Oncologia, Hospital Universitario Dr. Josep Trueta, Servicio de Oncologia,
🇪🇸Girona, Spain
Clinica Universidad de Navarra en Madrid
🇪🇸Madrid, Spain
Hospital Universitario Ramon y Cajal, Servicio de Oncologia Médica
🇪🇸Madrid, Spain
Fundació Institut d'Investigació Sanitària Illes Balears - IdISBa, Hospital Universitari Son Espases
🇪🇸Palma De Mallorca, Spain
Kantonsspital Frauenfeld - Frauenklinik
🇨🇭Frauenfeld, Switzerland
UniversitätsSpital Zürich - Klinik für Gynäkologie
🇨🇭Zürich, Switzerland
Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
University of Colorado Denver
🇺🇸Aurora, Colorado, United States
AdventHealth Cancer Institute
🇺🇸Orlando, Florida, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States