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)

Sponsor

NovoCure Ltd. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03940196

Collaborator

(none)

540

Enrollment

119

Locations

Arms

53.4

Anticipated Duration (Months)

4.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer	Device: NovoTTF-100L(O) Drug: Paclitaxel	Phase 3

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:

Patients receive TTFields at 200 kHz to the abdomen and pelvis using the NovoTTF-100L(O) System together with weekly paclitaxel.
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 Design

Study Type:

Interventional

Actual Enrollment :

540 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 22, 2019

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Sep 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NovoTTF-100L(O) Patients receive TTFields using the NovoTTF-100L(O) System together with weekly Paclitaxel	Device: NovoTTF-100L(O) 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 Drug: 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: Weekly Paclitaxel Taxol
Active Comparator: Best Standard of Care Patients receive best standard of care with weekly Paclitaxel	Drug: 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: Weekly Paclitaxel Taxol

Arm

Intervention/Treatment

Experimental: NovoTTF-100L(O)

Patients receive TTFields using the NovoTTF-100L(O) System together with weekly Paclitaxel

Device: NovoTTF-100L(O)

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

Drug: 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:

Weekly Paclitaxel

Taxol

Active Comparator: Best Standard of Care

Patients receive best standard of care with weekly Paclitaxel

Drug: 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:

Weekly Paclitaxel

Taxol

Outcome Measures

Primary Outcome Measures

Overall survival [4 years]

Secondary Outcome Measures

Progression-free survival [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 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
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
Quality of life using the EORTC QLQ C30 questionnaire with the ovarian cancer symptom OV28 module. [4 years]
Severity and frequency of adverse events [4 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology- Biltmore Cancer Center	Phoenix	Arizona	United States	85016
2	Arizona Oncology	Tucson	Arizona	United States	85711
3	University of California	La Jolla	California	United States	92093-1503
4	Hoag Memorial Hospital Presbyterian	Newport Beach	California	United States	92663
5	California Pacific Medical Center- Pacific Campus	San Francisco	California	United States	94109
6	Olive View - UCLA Medical Center	Sylmar	California	United States	91342
7	Rocky Mountain Cancer Centers	Aurora	Colorado	United States	80012
8	University of Colorado Denver	Aurora	Colorado	United States	80045-2517
9	Rocky Mountain Cancer Centers	Boulder	Colorado	United States	80303
10	Rocky Mountain Cancer Centers	Colorado Springs	Colorado	United States	80907
11	Rocky Mountain Cancer Centers	Denver	Colorado	United States	80218
12	Rocky Mountain Cancer Centers	Denver	Colorado	United States	80220
13	Rocky Mountain Cancer Centers	Lakewood	Colorado	United States	80228
14	Rocky Mountain Cancer Centers	Littleton	Colorado	United States	80120-4413
15	Rocky Mountain Cancer Centers	Lone Tree	Colorado	United States	80124
16	Rocky Mountain Cancer Centers	Longmont	Colorado	United States	80501
17	Rocky Mountain Cancer Centers	Parker	Colorado	United States	80138
18	Rocky Mountain Cancer Centers	Pueblo	Colorado	United States	81008
19	Rocky Mountain Cancer Centers	Thornton	Colorado	United States	80260
20	Broward Health Medical Center	Fort Lauderdale	Florida	United States	33316
21	AdventHealth Cancer Institute	Orlando	Florida	United States	32804
22	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
23	Rush University Cancer Center - Chicago and Innovation	Chicago	Illinois	United States	60612-3833
24	Des Moines Oncology Research Association	Des Moines	Iowa	United States	50309
25	Norton Cancer Institute	Louisville	Kentucky	United States	40202-2025
26	Maryland Oncology Hematology, P.A.	Silver Spring	Maryland	United States	20902
27	Lahey Hospital & Medical Center	Burlington	Massachusetts	United States	01805
28	Minnesota Oncology Hematology, PA	Saint Paul	Minnesota	United States	55102
29	Washington University School of Medicine in St. Louis	Saint Louis	Missouri	United States	63110-1010
30	Methodist Estabrook Cancer Center	Omaha	Nebraska	United States	68114-4108
31	Women's Cancer Center of Nevada	Las Vegas	Nevada	United States	89169
32	Center of Hope at Renown Medical Center	Reno	Nevada	United States	89502
33	MD Anderson Cancer Center at Cooper	Camden	New Jersey	United States	08103
34	The Valley Hospital	Paramus	New Jersey	United States	07652
35	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina	United States	27157
36	Miami Valley Hospital South	Centerville	Ohio	United States	45459-447
37	The Ohio State University Wexner Medical Center	Columbus	Ohio	United States	43210-1240
38	Northwest Cancer Specialists, PC	Portland	Oregon	United States	97227
39	West Penn OB/GYN	Pittsburgh	Pennsylvania	United States	15212
40	UPMC Cancer Center	Pittsburgh	Pennsylvania	United States	15232
41	Abington Hospital- Asplundh Cancer Pavilion	Willow Grove	Pennsylvania	United States	19001-3720
42	Women & Infants Hospital of Rhode Island	Providence	Rhode Island	United States	02905-2401
43	Sanford Gynecologic Oncology Clinic	Sioux Falls	South Dakota	United States	57104
44	Texas Oncology Austin-Balcones	Austin	Texas	United States	78731
45	Texas Oncology Austin-Midtown	Austin	Texas	United States	78745
46	Texas Oncology Austin-North Austin	Austin	Texas	United States	78758
47	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75216
48	Texas Oncology	Dallas	Texas	United States	75246
49	Texas Oncology-Fort Worth	Fort Worth	Texas	United States	76104-2150
50	The University of Texas Medical School at Houston	Houston	Texas	United States	77030-1501
51	Texas Oncology-McAllen	McAllen	Texas	United States	78503
52	Texas Oncology San Antonio Medical Center	San Antonio	Texas	United States	78240
53	Texas Oncology - Sugar Land	Sugar Land	Texas	United States	77479-4308
54	Texas Oncology	The Woodlands	Texas	United States	77380
55	Texas Oncology-Tyler	Tyler	Texas	United States	75702
56	Texas Oncology-Deke Slayton Cancer Center	Webster	Texas	United States	77598
57	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
58	Carilion Clinic-Gynecologic Oncology	Roanoke	Virginia	United States	24016-4962
59	Multicare Institute for Research and Innovation	Tacoma	Washington	United States	98405
60	KH der Barmherzigen Brüder Graz	Graz		Austria	8020
61	Univ.-Klinik für Gynäkologie und Geburtshilfe	Graz		Austria	8036
62	Univ.-Klinik für Gynäkologie und Geburtshilfe, Innsbruck	Innsbruck		Austria
63	Landesfrauenklinik Salzburg	Salzburg		Austria	5020
64	Imelda Ziekenhuis Bonheiden	Bonheiden		Belgium	2820
65	Cliniques Universitaires Saint Luc, Institut Roi Albert II	Brussel		Belgium	1200
66	Grand Hôpital de Charleroi, Oncologie-Hématologie	Charleroi		Belgium	6000
67	AZ Maria Middelares, Clinical Trial Unit Medical Oncology - Integrated Cancer Center Ghent	Gent		Belgium	9000
68	UZ Gent	Gent		Belgium	9000
69	University Hospitals Leuven, Leuven Cancer Institute	Leuven		Belgium
70	CHU Ambroise Paré	Mons		Belgium	7000
71	CHU UCL Namur - Site Ste Elisabeth	Namur		Belgium	5000
72	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E)V9
73	Centre Hospitalie	Montréal	Quebec	Canada	H2X 0A9
74	Tom Baker Cancer Center	Calgary		Canada	H2L 4M1
75	McGill University Health Centre	Montréal		Canada	H4A 3J1
76	Jewish General Hospital	Montréal		Canada	QC H3T 1E2
77	Onkologická Klinika Fakultní nemocnice Olomouc	Olomouc		Czechia	779 00
78	University Hospital Ostrava	Ostrava-Poruba		Czechia	708 52
79	Gynekologicko-porodnická klinika, Fakultní nemocnice Královské Vinohrady	Praha 10		Czechia	100 34
80	Gynekologicko-porodnická klinika 1. LF UK a VFN	Praha 2		Czechia	128 01
81	Gynekologicko-porodnické oddělení - Nemocnice České Budějovice a.s.	České Budějovice		Czechia	370 01
82	Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Klinik für Gynäkologie	Berlin		Germany	1200
83	Universitätsklinikum Carl Gustav Carus	Dresden		Germany	01307
84	Horst-Schmidt-Kliniken, Gynecology and Gynecologic, Oncology Department	Wiesbaden		Germany	65199
85	Semmelweis University	Budapest		Hungary	1085
86	Nőgyógyászati Osztály, Országos Onkológiai Intézet	Budapest		Hungary	1122
87	Szuleszeti és Nogyogyaszati Klinika	Debrecen		Hungary	4032
88	Hillel Yaffe Medical Center	Hadera		Israel	38100
89	Saare Zedek Medical Center - Gyneco-Oncology	Jerusalem		Israel	9103102
90	Oncology Institute, Galilee Medical Center	Nahariya		Israel	22100
91	Gyneco-Oncology Chaim Sheba Medical Center	Ramat Gan		Israel	5265601
92	Policlinico S. Orsola-Malpighi, SSD Oncologia Medica Addarii	Bologna		Italy	40138
93	Presidio Ospedaliero Antonio Perrino - ASL Brindisi	Brindisi		Italy	72100
94	ASST Lecco - Ospedale Manzoni, Dipartimento Oncologico	Lecco		Italy	23900
95	Dipartimento Medicina e Chirurgia, Università Milano-Bicocca, Direttore Programma Ginecologia Oncologica, Istituto Europeo Oncologia	Milano		Italy	20141
96	IRCCS Ospedale San Raffaele, U.O. Ginecologia-Ematologia e TMO	Milano		Italy	60 20132
97	Istituto Nazionale Tumori IRCCS Fondazione Pascale	Napoli		Italy	80130
98	Fondazione Policlinico Universitario Gemelli	Roma		Italy	00168
99	University Saint Anna	Torino		Italy	10126
100	Amsterdam Universitair Medische centra	Amsterdam		Netherlands	1105
101	University Medical Center Utrech	Utrecht		Netherlands	3508
102	Szpitale Pomorskie Sp. z o.o.	Gdynia		Poland	81-519
103	Oddział Kliniczny Chirurgii Ogólnej i Onkologicznej, Szpital Św. Rafała	Kraków		Poland	30-693
104	Uniwersytet Medyczny w Lublinie, I Klinika Ginekologii Onkologicznej i Ginekologii	Lublin		Poland	20-081
105	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	10-228
106	Oddział Ginekologii Onkologicznej Katedry i Kliniki Onkologii Uniwersytetu Medycznego w Poznaniu	Poznań		Poland	60-569
107	Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie, Klinika Ginekologii Operacyjnej i Onkologii Ginekologicznej Dorosłych i Dziewcząt	Szczecin		Poland	70-111
108	Szpital Kliniczny im. ks. Anny Mazowieckiej	Warsaw		Poland	00-315
109	Servicio de Oncología Médica, Hospital Universitario Quirón Dexeus	Barcelona		Spain	08028
110	lnstitut Catala d'Oncologia, Hospital Universitario Dr. Josep Trueta, Servicio de Oncologia,	Girona		Spain	17007
111	Clinica Universidad de Navarra en Madrid	Madrid		Spain	28027
112	Hospital MD Anderson Cancer Center	Madrid		Spain	28033
113	Hospital Universitario Ramon y Cajal, Servicio de Oncologia Médica	Madrid		Spain	28034
114	Hospital 12 de Octubre. Servicio Oncología Médica	Madrid		Spain	28041
115	Fundació Institut d'Investigació Sanitària Illes Balears - IdISBa, Hospital Universitari Son Espases	Palma De Mallorca		Spain	07120
116	Gynecological Tumor Center, University Hospital Basel	Basel		Switzerland	4031
117	IOSI Bellinzona, Oncology Institute of Southern Switzerland, Ospedale San Giovanni	Bellinzona		Switzerland	6500
118	Kantonsspital Frauenfeld - Frauenklinik	Frauenfeld		Switzerland	8501
119	UniversitätsSpital Zürich - Klinik für Gynäkologie	Zürich		Switzerland	8091