Phase II study of oral ridaforolimus in patients with metastatic and/or locally advanced recurrent endometrial cancer: NCIC CTG IND 192.

5013 Background: Loss of PTEN function occurs in 26-83% of endometrial carcinomas (EC) leading to deregulation of PI3K/AKT/mTOR signaling. Intravenous (IV) inhibitors of mTOR have demonstrated activity in advanced EC. Ridaforolimus is an orally administered analog of rapamycin that inhibits mTOR. Methods: NCIC CTG conducted a 2-stage phase II study to assess the activity (objective response) of ridaforolimus in women with measurable EC. Prior hormonal therapy, radiotherapy and adjuvant chemotherapy were allowed. Patients (pts) received ridaforolimus 40 mg PO daily x 5 days per week in 4 week cycles. Tumor response was assessed every 2 cycles. Results: 35 pts were enrolled; 1 pt cancelled without receiving treatment. Of the remaining 34, 33 are now evaluable for safety and 26 for response. Follow-up is ongoing. 11 pts had received prior chemo-, 7 hormonal and 22 radio-therapy. Median age was 63 (range 43-89) yrs; 7 pts had adenocarcinoma, 21 endometrioid, 4 serous and 2 mixed histology. 113 (range 1-13) cy...