An open, multicenter phase II trial of extend-release onapristone in patients with progesterone receptor–positive recurrent granulosa cell ovarian cancer, low-grade serous ovarian/primary peritoneal cancer, or endometroid endometrial cancer will demonstrate if the investigational drug will shrink or stop the cancer.
An open, multicenter phase II trial (NCT03909152) of extend-release (ER) onapristone (Apristor) in patients with progesterone receptorpositive (PR+) recurrent granulosa cell ovarian cancer, low-grade serous ovarian/primary peritoneal cancer, or endometroid endometrial cancer will demonstrate if the investigational drug will shrink or stop the cancer.
In the basket study involving onapristone ER, 84 women will receive 50 mg of the drug by mouth twice daily for a 28-day cycle. The cycles will continue until disease progression, unacceptable toxicity, or if the patient decides to withdraw consent. The first patients being enrolled will have low-grade serous ovarian cancer.
The primary end point is response rate within 36 weeks of starting on onapristone ER, which will be determined by RECIST 1.1 response. All the patients will be treated at 1 of the Memorial Sloan Kettering locations.
Newly diagnosed and relapsed/refractory patients are eligible for the trial. Additionally, eligible patients will have PR+ recurrent granulosa cell ovarian cancer, low-grade serous ovarian/primary peritoneal cancer, or endometroid endometrial cancer who have been treated with 1 prior chemotherapy regimen at least 3 weeks previously.
In a previous clinical trial involving patients with metastatic breast cancer, onapristone ER monotherapy had an overall response rate (ORR) of 56%, a 17.5-month duration of response, and median progression-free survival of 14 months.1Another trial of onapristone ER had a 25% ORR and 50% clinical benefit rate (CBR) in patients with tamoxifen-resistant breast cancer.2In the most recent phase I trial, heavily pre-treated patients had a CBR of 17%.3
The 3 selected gynecologic cancers are driven by progesterone, which is the hormone responsible for regulating the menstrual cycle. This study will assess if onapristone ER, a progesterone antagonist, can shrink the cancer or stop cancer cells from growing and spreading.4
The manufacturer, Context Therapeutics, is also planning a prospective phase II multicenter trial of fulvestrant (Faslodex) and onapristone compared with fulvestrant alone in patients with estrogen receptorpositive, progesterone receptor–positive, HER2-negative metastatic breast cancer after they have progressed on a combination therapy of a CDK4/6 inhibitor and an aromatase inhibitor.