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)

April 19, 2022 updated by: NovoCure Ltd.

ENGOT-ov50 / GOG-3029 / INNOVATE-3: Pivotal, Randomized, Open-label Study of Tumor Treating Fields (TTFields, 200kHz) Concomitant With Weekly Paclitaxel for the Treatment of Recurrent Ovarian Cancer

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.

Study Overview

Status

Active, not recruiting

Conditions

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.

Study Type

Interventional

Enrollment (Actual)

540

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Graz, Austria, 8020
        • KH der Barmherzigen Brüder Graz
      • Graz, Austria, 8036
        • Univ.-Klinik für Gynäkologie und Geburtshilfe
      • Innsbruck, Austria
        • Univ.-Klinik für Gynäkologie und Geburtshilfe, Innsbruck
      • Salzburg, Austria, 5020
        • Landesfrauenklinik Salzburg
      • Bonheiden, Belgium, 2820
        • Imelda Ziekenhuis Bonheiden
      • Brussel, Belgium, 1200
        • Cliniques Universitaires Saint Luc, Institut Roi Albert II
      • Charleroi, Belgium, 6000
        • Grand Hôpital de Charleroi, Oncologie-Hématologie
      • Gent, Belgium, 9000
        • UZ Gent
      • Gent, Belgium, 9000
        • AZ Maria Middelares, Clinical Trial Unit Medical Oncology - Integrated Cancer Center Ghent
      • Leuven, Belgium
        • University Hospitals Leuven, Leuven Cancer Institute
      • Mons, Belgium, 7000
        • CHU Ambroise Paré
      • Namur, Belgium, 5000
        • CHU UCL Namur - Site Ste Elisabeth
      • Calgary, Canada, H2L 4M1
        • Tom Baker Cancer Center
      • Montréal, Canada, H4A 3J1
        • McGill University Health Centre
      • Montréal, Canada, QC H3T 1E2
        • Jewish General Hospital
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E)V9
        • CancerCare Manitoba
    • Quebec
      • Montréal, Quebec, Canada, H2X 0A9
        • Centre Hospitalie
      • Olomouc, Czechia, 779 00
        • Onkologická klinika Fakultní nemocnice Olomouc
      • Ostrava-Poruba, Czechia, 708 52
        • University Hospital Ostrava
      • Praha 10, Czechia, 100 34
        • Gynekologicko-porodnická klinika, Fakultní nemocnice Královské Vinohrady
      • Praha 2, Czechia, 128 01
        • Gynekologicko-porodnická klinika 1. LF UK a VFN
      • České Budějovice, Czechia, 370 01
        • Gynekologicko-porodnické oddělení - Nemocnice České Budějovice a.s.
      • Berlin, Germany, 1200
        • Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Klinik für Gynäkologie
      • Dresden, Germany, 01307
        • Universitätsklinikum Carl Gustav Carus
      • Wiesbaden, Germany, 65199
        • Horst-Schmidt-Kliniken, Gynecology and Gynecologic, Oncology Department
      • Budapest, Hungary, 1085
        • Semmelweis University
      • Budapest, Hungary, 1122
        • Nőgyógyászati Osztály, Országos Onkológiai Intézet
      • Debrecen, Hungary, 4032
        • Szuleszeti és Nogyogyaszati Klinika
      • Hadera, Israel, 38100
        • Hillel Yaffe Medical Center
      • Jerusalem, Israel, 9103102
        • Saare Zedek Medical Center - Gyneco-Oncology
      • Nahariya, Israel, 22100
        • Oncology Institute, Galilee Medical Center
      • Ramat Gan, Israel, 5265601
        • Gyneco-Oncology Chaim Sheba Medical Center
      • Bologna, Italy, 40138
        • Policlinico S. Orsola-Malpighi, SSD Oncologia Medica Addarii
      • Brindisi, Italy, 72100
        • Presidio Ospedaliero Antonio Perrino - ASL Brindisi
      • Lecco, Italy, 23900
        • ASST Lecco - Ospedale Manzoni, Dipartimento Oncologico
      • Milano, Italy, 20141
        • Dipartimento Medicina e Chirurgia, Università Milano-Bicocca, Direttore Programma Ginecologia Oncologica, Istituto Europeo Oncologia
      • Milano, Italy, 60 20132
        • IRCCS Ospedale San Raffaele, U.O. Ginecologia-Ematologia e TMO
      • Napoli, Italy, 80130
        • Istituto Nazionale Tumori IRCCS Fondazione Pascale
      • Roma, Italy, 00168
        • Fondazione Policlinico Universitario Gemelli
      • Torino, Italy, 10126
        • University Saint Anna
      • Amsterdam, Netherlands, 1105
        • Amsterdam Universitair Medische Centra
      • Utrecht, Netherlands, 3508
        • University Medical Center Utrech
      • Gdynia, Poland, 81-519
        • Szpitale Pomorskie Sp. z o.o.
      • Kraków, Poland, 30-693
        • Oddział Kliniczny Chirurgii Ogólnej i Onkologicznej, Szpital Św. Rafała
      • Lublin, Poland, 20-081
        • Uniwersytet Medyczny w Lublinie, I Klinika Ginekologii Onkologicznej i Ginekologii
      • Olsztyn, Poland, 10-228
        • Samodzielny Publiczny Zakład Opieki Zdrowotnej MSWiA z Warmińsko-Mazurskim Centrum Onkologii w Olsztynie, Oddział Kliniczny Onkologii i Immunoonkologii z Ośrodkiem Dziennym Terapii Onkologicznej
      • Poznań, Poland, 60-569
        • Oddział Ginekologii Onkologicznej Katedry i Kliniki Onkologii Uniwersytetu Medycznego w Poznaniu
      • Szczecin, Poland, 70-111
        • Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie, Klinika Ginekologii Operacyjnej i Onkologii Ginekologicznej Dorosłych i Dziewcząt
      • Warsaw, Poland, 00-315
        • Szpital Kliniczny im. Ks. Anny Mazowieckiej
      • Barcelona, Spain, 08028
        • Servicio de Oncología Médica, Hospital Universitario Quirón Dexeus
      • Girona, Spain, 17007
        • lnstitut Catala d'Oncologia, Hospital Universitario Dr. Josep Trueta, Servicio de Oncologia,
      • Madrid, Spain, 28027
        • Clinica Universidad de Navarra en Madrid
      • Madrid, Spain, 28033
        • Hospital MD Anderson Cancer Center
      • Madrid, Spain, 28034
        • Hospital Universitario Ramón y Cajal, Servicio de Oncologia Médica
      • Madrid, Spain, 28041
        • Hospital 12 de Octubre. Servicio Oncología Médica
      • Palma De Mallorca, Spain, 07120
        • Fundació Institut d'Investigació Sanitària Illes Balears - IdISBa, Hospital Universitari Son Espases
      • Basel, Switzerland, 4031
        • Gynecological Tumor Center, University Hospital Basel
      • Bellinzona, Switzerland, 6500
        • IOSI Bellinzona, Oncology Institute of Southern Switzerland, Ospedale San Giovanni
      • Frauenfeld, Switzerland, 8501
        • Kantonsspital Frauenfeld - Frauenklinik
      • Zürich, Switzerland, 8091
        • UniversitätsSpital Zürich - Klinik für Gynäkologie
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Arizona Oncology- Biltmore Cancer Center
      • Tucson, Arizona, United States, 85711
        • Arizona Oncology
    • California
      • La Jolla, California, United States, 92093-1503
        • University of California
      • Newport Beach, California, United States, 92663
        • Hoag Memorial Hospital Presbyterian
      • San Francisco, California, United States, 94109
        • California Pacific Medical Center- Pacific Campus
      • Sylmar, California, United States, 91342
        • Olive View - UCLA Medical Center
    • Colorado
      • Aurora, Colorado, United States, 80012
        • Rocky Mountain Cancer Centers
      • Aurora, Colorado, United States, 80045-2517
        • University of Colorado Denver
      • Boulder, Colorado, United States, 80303
        • Rocky Mountain Cancer Centers
      • Colorado Springs, Colorado, United States, 80907
        • Rocky Mountain Cancer Centers
      • Denver, Colorado, United States, 80218
        • Rocky Mountain Cancer Centers
      • Denver, Colorado, United States, 80220
        • Rocky Mountain Cancer Centers
      • Lakewood, Colorado, United States, 80228
        • Rocky Mountain Cancer Centers
      • Littleton, Colorado, United States, 80120-4413
        • Rocky Mountain Cancer Centers
      • Lone Tree, Colorado, United States, 80124
        • Rocky Mountain Cancer Centers
      • Longmont, Colorado, United States, 80501
        • Rocky Mountain Cancer Centers
      • Parker, Colorado, United States, 80138
        • Rocky Mountain Cancer Centers
      • Pueblo, Colorado, United States, 81008
        • Rocky Mountain Cancer Centers
      • Thornton, Colorado, United States, 80260
        • Rocky Mountain Cancer Centers
    • Florida
      • Fort Lauderdale, Florida, United States, 33316
        • Broward Health Medical Center
      • Orlando, Florida, United States, 32804
        • AdventHealth Cancer Institute
    • Georgia
      • Gainesville, Georgia, United States, 30501
        • Northeast Georgia Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60612-3833
        • Rush University Cancer Center - Chicago and Innovation
    • Iowa
      • Des Moines, Iowa, United States, 50309
        • Des Moines Oncology Research Association
    • Kentucky
      • Louisville, Kentucky, United States, 40202-2025
        • Norton Cancer Institute
    • Maryland
      • Silver Spring, Maryland, United States, 20902
        • Maryland Oncology Hematology, P.A.
    • Massachusetts
      • Burlington, Massachusetts, United States, 01805
        • Lahey Hospital & Medical Center
    • Minnesota
      • Saint Paul, Minnesota, United States, 55102
        • Minnesota Oncology Hematology, Pa
    • Missouri
      • Saint Louis, Missouri, United States, 63110-1010
        • Washington University School of Medicine in St. Louis
    • Nebraska
      • Omaha, Nebraska, United States, 68114-4108
        • Methodist Estabrook Cancer Center
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Women's Cancer Center of Nevada
      • Reno, Nevada, United States, 89502
        • Center of Hope at Renown Medical Center
    • New Jersey
      • Camden, New Jersey, United States, 08103
        • MD Anderson Cancer Center at Cooper
      • Paramus, New Jersey, United States, 07652
        • The Valley Hospital
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest Baptist Medical Center
    • Ohio
      • Centerville, Ohio, United States, 45459-447
        • Miami Valley Hospital South
      • Columbus, Ohio, United States, 43210-1240
        • The Ohio State University Wexner Medical Center
    • Oregon
      • Portland, Oregon, United States, 97227
        • Northwest Cancer Specialists, PC
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC Cancer Center
      • Pittsburgh, Pennsylvania, United States, 15212
        • West Penn OB/GYN
      • Willow Grove, Pennsylvania, United States, 19001-3720
        • Abington Hospital- Asplundh Cancer Pavilion
    • Rhode Island
      • Providence, Rhode Island, United States, 02905-2401
        • Women & Infants Hospital of Rhode Island
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57104
        • Sanford Gynecologic Oncology Clinic
    • Texas
      • Austin, Texas, United States, 78731
        • Texas Oncology Austin-Balcones
      • Austin, Texas, United States, 78745
        • Texas Oncology Austin-Midtown
      • Austin, Texas, United States, 78758
        • Texas Oncology Austin-North Austin
      • Dallas, Texas, United States, 75246
        • Texas Oncology
      • Dallas, Texas, United States, 75216
        • University of Texas Southwestern Medical Center
      • Fort Worth, Texas, United States, 76104-2150
        • Texas Oncology-Fort Worth
      • Houston, Texas, United States, 77030-1501
        • The University of Texas Medical School at Houston
      • McAllen, Texas, United States, 78503
        • Texas Oncology-McAllen
      • San Antonio, Texas, United States, 78240
        • Texas Oncology San Antonio Medical Center
      • Sugar Land, Texas, United States, 77479-4308
        • Texas Oncology - Sugar Land
      • The Woodlands, Texas, United States, 77380
        • Texas Oncology
      • Tyler, Texas, United States, 75702
        • Texas Oncology-Tyler
      • Webster, Texas, United States, 77598
        • Texas Oncology-Deke Slayton Cancer Center
    • Virginia
      • Norfolk, Virginia, United States, 23502
        • Virginia Oncology Associates
      • Roanoke, Virginia, United States, 24016-4962
        • Carilion Clinic-Gynecologic Oncology
    • Washington
      • Tacoma, Washington, United States, 98405
        • MultiCare Institute for Research and Innovation

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. 18 years of age and older
  2. Epithelial histology of ovarian/primary peritoneal or fallopian tube carcinoma at the time of diagnosis
  3. Life expectancy of ≥ 12 weeks
  4. Maximum two prior lines of systemic therapy following diagnosis of platinum-resistance
  5. Maximum total of 5 prior lines of systemic therapy
  6. Amenable to receive weekly paclitaxel and able to operate the NovoTTF-100L(O) System
  7. ECOG 0-1
  8. Evaluable (measurable or non-measurable) disease in the abdominal/pelvic region per RECIST V1.
  9. Signed informed consent form for the study protocol

Exclusion Criteria:

  1. 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
  2. Prior disease progression on a weekly paclitaxel for recurrent disease
  3. Brain metastasis or leptomeningeal spread of the tumor
  4. Albumin level <25 gram/liter (subjects should not receive total parenteral nutrition or albumin within 2 weeks of the test)
  5. CTCAE V5.0 Grade 3 or higher peripheral neuropathy
  6. Implantable electrical medical devices
  7. Known allergies to medical adhesives or hydrogel
  8. 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
  9. 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
  10. Serious co-morbidities
  11. Concurrent anti-tumor therapy beyond weekly paclitaxel, excluding hormonal therapy for breast cancer
  12. Concurrent active treatment in another clinical trial. However prior participation in clinical trials is allowed as well as participation during survival follow-up
  13. 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
  14. Admitted to an institution by administrative or court order

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NovoTTF-100L(O)
Patients receive TTFields using the NovoTTF-100L(O) System together with weekly Paclitaxel
Patients receive continuous TTFields treatment using the NovoTTF-100L(O) device. TTFields treatment will consist of wearing four electrically insulated electrode arrays on the abdomen/pelvis. The treatment enables the patient to maintain regular daily routine.
Other Names:
  • TTFields
Paclitaxel 80 mg/m^2 intravenous infusion will be administered weekly for 8 weeks and then on Days 1, 8 and 15 of each subsequent 28-day cycle.
Other Names:
  • Taxol
  • Weekly Paclitaxel
Active Comparator: Best Standard of Care
Patients receive best standard of care with weekly Paclitaxel
Paclitaxel 80 mg/m^2 intravenous infusion will be administered weekly for 8 weeks and then on Days 1, 8 and 15 of each subsequent 28-day cycle.
Other Names:
  • Taxol
  • Weekly Paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: 4 years
4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival
Time Frame: 4 years
4 years
Objective response rate
Time Frame: 4 years
4 years
Next progression-free survival
Time Frame: 4 years
Measured from the time of randomization to tumor progression on next-line treatment
4 years
Time to undisputable deterioration in health-related quality of life (HRQoL)
Time Frame: 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
4 years
Time to first and second subsequent treatment
Time Frame: 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
4 years
Quality of life using the EORTC QLQ C30 questionnaire with the ovarian cancer symptom OV28 module.
Time Frame: 4 years
4 years
Severity and frequency of adverse events
Time Frame: 4 years
4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Ignace Vergote, MD, University Hospitals Leuven, Leuven Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 22, 2019

Primary Completion (Anticipated)

September 1, 2023

Study Completion (Anticipated)

September 1, 2023

Study Registration Dates

First Submitted

April 29, 2019

First Submitted That Met QC Criteria

May 3, 2019

First Posted (Actual)

May 7, 2019

Study Record Updates

Last Update Posted (Actual)

April 20, 2022

Last Update Submitted That Met QC Criteria

April 19, 2022

Last Verified

April 1, 2022

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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