Abstract CT174: Phase III INNOVATE study of tumor treating fields (200 kHz) concomitant with weekly paclitaxel for platinum-resistant ovarian cancer (ENGOT-ov50/BGOG study groups)

Abstract

Abstract Background: Tumor Treating Fields (TTFields) are a non-invasive, regional antimitotic treatment modality approved for glioblastoma by the FDA. TTFields act by disrupting mitotic spindle formation during metaphase. In multiple preclinical models of ovarian cancer, TTFields (200 kHz) reduced viability of cell lines through apoptosis. TTFields have demonstrated synergistic effects with taxanes in vitro and in vivo. The Phase II INNOVATE clinical study [NCT02244502] demonstrated the safety of TTFields combined with weekly paclitaxel in 31 PROC (platinum-resistant ovarian cancer) patients. No serious adverse events related to TTFields were reported. There was no increase in grade 3-4 adverse events compared to the frequency of such events reported in the literature with single agent weekly paclitaxel. Twenty-six patients (84%) had TTFields-related dermatitis but only one patient permanently discontinued TTFields due to dermatitis. The median PFS was 8.9 months, 7 patients (25%) had partial response and the clinical benefit rate was 71%. The median overall survival was not reached: the one-year survival rate was 61%. In this Phase III INNOVATE-3 [ENGOT-ov50], we study TTFields combined with weekly paclitaxel in PROC patients. Study Design: Patients (N=540) with PROC (progression per RECIST V1.1) within 6 months of last platinum therapy with a maximum of two to five prior lines of systemic therapy will be enrolled. Patients (ECOG score of 0-1) will have no peripheral neuropathy. Patients with primary refractory disease (progression during first line therapy) will be excluded. Patients will be randomized in a ratio of 1:1 to receive either weekly paclitaxel alone or weekly paclitaxel in combination with TTFields (200 kHz). Weekly paclitaxel will be administered at standard starting of dose 80 mg/m2 weekly for 8 weeks, and then on Days 1, 8, and 15 for each subsequent 28-day cycle. TTFields will be applied in the experimental arm for at least 18 hours/day on average, and maybe continued as long as there is no progression in the abdominal or pelvic regions (“in-field region”) per RECIST V1.1. Clinical follow up will be performed q4w, with radiological follow up (CT or MRI scans of the abdomen and chest) q8w. The primary endpoint will be overall survival. Main secondary endpoints will include progression-free survival, objective response rate, severity and frequency of adverse events and quality of life based on EORTC QLQ-C30 with the QLQ-OV28 questionnaire. A sample size of 540 patients is sufficient to detect an increase in median overall survival from 12 to 16 months (Hazard ratio 0.75). Citation Format: Ignace Vergote. Phase III INNOVATE study of tumor treating fields (200 kHz) concomitant with weekly paclitaxel for platinum-resistant ovarian cancer (ENGOT-ov50/BGOG study groups) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT174.