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Effect of Tumor Treating Fields (TTFields, 200 kHz) Concomitant With Weekly Paclitaxel for the Treatment of Platinum-resistant Ovarian Cancer (PROC) (ENGOT-ov50 / GOG-3029 / INNOVATE-3)

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ClinicalTrials.gov Identifier: NCT03940196
Recruitment Status : Recruiting
First Posted : May 7, 2019
Last Update Posted : January 2, 2020
Sponsor:
Information provided by (Responsible Party):
NovoCure Ltd.

Tracking Information
First Submitted Date  ICMJE April 29, 2019
First Posted Date  ICMJE May 7, 2019
Last Update Posted Date January 2, 2020
Actual Study Start Date  ICMJE March 22, 2019
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 3, 2019)
Overall survival [ Time Frame: 4 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03940196 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2019)
  • Progression-free survival [ Time Frame: 4 years ]
  • Objective response rate [ Time Frame: 4 years ]
  • Next progression-free survival [ Time Frame: 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) [ 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
  • 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
  • Quality of life using the EORTC QLQ C30 questionnaire with the ovarian cancer symptom OV28 module. [ Time Frame: 4 years ]
  • Severity and frequency of adverse events [ Time Frame: 4 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Tumor Treating Fields (TTFields, 200 kHz) Concomitant With Weekly Paclitaxel for the Treatment of Platinum-resistant Ovarian Cancer (PROC) (ENGOT-ov50 / GOG-3029 / INNOVATE-3)
Official Title  ICMJE 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 Platinum-resistant Ovarian Cancer (PROC)
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 platinum-resistant ovarian cancer (PROC). 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Ovarian Cancer
Intervention  ICMJE
  • 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 Name: 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
Study Arms  ICMJE
  • Experimental: NovoTTF-100L(O)
    Patients receive TTFields using the NovoTTF-100L(O) System together with weekly Paclitaxel
    Interventions:
    • Device: NovoTTF-100L(O)
    • Drug: Paclitaxel
  • Active Comparator: Best Standard of Care
    Patients receive best standard of care with weekly Paclitaxel
    Intervention: Drug: Paclitaxel
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 3, 2019)
540
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2024
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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. Eastern Cooperative Oncology Group (ECOG) score 0-1
  8. Prior clinical trials are allowed
  9. Evaluable (measurable or non-measurable) disease in the abdominal/pelvic region per RECIST V1.1
  10. 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)
  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
  5. CTCAE V5.0 Grade 3 or higher peripheral neuropathy
  6. Implantable electronic medical devices in the torso
  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
  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 or cervix of the uterus
  10. Serious co-morbidities
  11. Concurrent anti-tumor therapy beyond weekly paclitaxel
  12. Pregnancy or breast-feeding
  13. Admitted to an institution by administrative or court order
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Antonia Mahnig clinicaltrials@novocure.com
Listed Location Countries  ICMJE Austria,   Belgium,   Czechia,   Hungary,   Israel,   Italy,   Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03940196
Other Study ID Numbers  ICMJE EF-28
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party NovoCure Ltd.
Study Sponsor  ICMJE NovoCure Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Ignace Vergote, MD University Hospitals Leuven, Leuven Cancer Institute
PRS Account NovoCure Ltd.
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP