Novocure has initiated a Phase 3 trial investigating its Tumor Treating Fields (TTFields) — a method that uses electric fields to disrupt cell division — in combination with Taxol (paclitaxel) as a treatment for ovarian cancer patients who are resistant to platinum-based chemotherapy.
The trial — which is for women who received up to two prior lines of therapy after developing resistance to platinum-based chemotherapy — comes after promising findings from the INNOVATE Phase 2 trial (NCT02244502), where the combination more than doubled the time patients lived without disease worsening, compared with historical controls treated with Taxol alone.
Ovarian cancer, a disease that affects 22,500 women every year in the U.S., is often treated with a chemotherapy regimen containing a platinum agent, such as cisplatin or carboplatin. However, while most patients respond, the majority will see their cancer return or progress within a few months.
These patients — platinum-resistant ovarian cancer patients — have numerous therapies available, but survival rates are low.
“Ovarian cancer is one of the most aggressive forms of cancer,” Ignace Vergote, chairman of the department of obstetrics and gynaecology and gynaecologic oncology at the Catholic University of Leuven, in Belgium, said in a press release.
“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,” he added.
Taxol is another chemotherapy agent that leads to high response rates in platinum-resistant patients, and studies in the lab have shown that TTFields works in synergy with this chemotherapy to increase cancer cell death.
TTFields disrupts cancer cell division by delivering low intensity alternating electric fields and activating “suicide” programs in these cells. The therapy has been approved by the U.S. Food and Drug Administration as a noninvasive, regional treatment method for newly diagnosed glioblastoma, an aggressive type of brain cancer.
In ovarian cancer studies, results have also been promising. The Phase 2 INNOVATE trial showed that adding TTFields to Taxol is safe and extends the time a patient lives without disease worsening, from 3.9 months — in historical controls treated with Taxol alone — to 8.9 months.
TTFields was delivered by four electrodes placed on the torso in the region surrounding the tumor. Because the delivery system is portable, patients were able to maintain a regular daily routine.
In the trial, 25% responded to the combination, and 46% experienced stable disease, reaching a clinical benefit rate of 71%. Also, 61% of patients were alive after one year.
The next phase, INNOVATE-3, will determine if TTFields plus weekly Taxol is better than weekly Taxol alone at extending the survival of ovarian cancer patients with platinum-resistant disease. It will include 540 patients who will randomly receive TTFields, delivered at a 200 kHz frequency, plus weekly Taxol, or Taxol only. Researchers will also examine the time patients live without disease worsening, the severity and frequency of side effects, and any deterioration in quality of life.
“INNOVATE-3 is Novocure’s fourth phase 3 pivotal trial beyond glioblastoma, demonstrating our commitment to developing Tumor Treating Fields for a variety of solid tumors,” said Asaf Danziger, Novocure’s chief executive officer.
“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,” he added.
The trial is expected to enroll patients in centers across Europe, U.S., and Canada. More information is available on Novocure’s website here.