A pivotal phase III INNOVATE-3 trial investigating the efficacy of tumor-treating fields (TTFields; Optune) combined with paclitaxel in patients with recurrent, platinum-resistant ovarian cancer has been initiated, according to Novocure, the company developing the device.
A pivotal phase III INNOVATE-3 trial investigating the efficacy of tumor-treating fields (TTFields; Optune) combined with paclitaxel in patients with recurrent, platinum-resistant ovarian cancer has been initiated, according to Novocure, the company developing the device.1
The prospective, open-label study will randomize 540 patients with recurrent, platinum-resistant ovarian cancer to receive either paclitaxel alone or paclitaxel in combination with TTFields tuned to 200 kHz on a weekly schedule until disease progression.
The primary endpoint of the trial is overall survival (OS), with secondary endpoints of progression-free survival (PFS), objective response rate, severity and frequency of adverse events, time to undisputable deterioration in health-related quality of life or death, and quality of life.
Patients who have been previously treated with and not responded to paclitaxel and patients with brain metastases are not eligible to be included on the trial.
This phase III study was launched following positive findings from the phase II INNOVATE trial, which showed TTFields combined with weekly paclitaxel more than doubled progression-free survival (PFS) and improved overall survival (OS) in 31 evaluable patients compared with paclitaxel alone.2
This is the fourth phase III trial to study TTFields in solid tumors beyond glioblastoma.
“At Novocure, we strive to extend survival in some of the most aggressive forms of cancer. Ovarian cancer has been an important area of focus for our research because of the great unmet need faced by these patients. We are now working closely with trial sites and institutional review boards to open sites and enroll patients as quickly as possible,” said Asaf Danziger, Novocure’s chief executive officer.
The phase II INNOVATE study was a single-arm trial in which 31 patients received paclitaxel weekly for 8 weeks and then on days 1, 8, and 15 of each subsequent 28-day cycle at a starting dose of 80 mg/m. The primary endpoint of the study was safety and secondary endpoints were OS, PFS, and response rate.
The median patient age was 60 (range, 45-77), and the majority of patients (77%) had serous histology and an ECOG performance status of 0 (52%), while the remainder (48%) had an ECOG score of 1. All patients on the study had previously received platinum-based chemotherapy and 30 patients (97%) had received prior taxanes. The median number of chemotherapy lines patients had received previously was 4 (range, 1-11).
Results from the trial showed the median PFS was 8.9 months, with a clinical benefit rate of 71% and 7 patients (25%) achieving a partial response. The 1-year survival rate was 61%, and the median OS was not yet reached.
There were no serious adverse events (AEs) related to TTFields and no increase in grade 3/4 AEs compared to what has been seen with weekly paclitaxel alone. Twenty-six patients experienced dermatitis, which is expected with TTFields treatment, and 1 patient permanently discontinued due to dermatitis.
“Ovarian cancer is one of the most aggressive forms of cancer,” said investigator Ignace Vergote, MD, PhD, chairman of the Department of Obstetrics and Gynaecology and Gynaecologic Oncology at the Catholic University of Leuven in Belgium. “Most ovarian cancer patients are diagnosed at an advanced stage, which makes the disease difficult to treat. Current treatment options are not enough for these patients. We are pleased to begin this trial that has the potential to improve survival in recurrent ovarian cancer.”
TTFields was approved for use in combination with adjuvant temozolomide (Temodar) for the treatment of patients with newly diagnosed glioblastoma following surgery, chemotherapy, and radiation therapy. The device was also approved to treat patients with recurrent glioblastoma.
Novocure Initiates Phase III Pivotal Trial in Recurrent Ovarian Cancer. Novocure. Published March 22, 2019.https://bit.ly/2CCwvOY. Accessed March 25, 2019.Vergote I, von Moos R, Manso L, Van Nieuwenhuysen E, Concin N, Sessa C. Tumor Treating Fields in combination with paclitaxel in recurrent ovarian carcinoma: Results of the INNOVATE pilot study.Gynecologic Oncology. 2018; 150(3):471-477.