Abstract
e15661 Background: Biliary duct carcinoma is a rare but highly fatal malignancy. The five-year survival rate for advanced bile duct cancer is 2%, per SEER data. As such, new treatment options are desperately needed. CPI-613, a novel anticancer agent that selectively inhibits mitochondrial metabolism in cancer cells, was employed in this study. Methods: This phase 1 study utilized a two-stage dose-escalation schema to determine the maximum-tolerated dose (MTD) and safety of single agent CPI-613 in patients with locally advanced or metastatic bile duct cancers. The 1st cohort enrolled 4 patients at 2300 mg/m2, with no dose-limiting toxicities (DLT) observed. The 2nd cohort enrolled patients at 1200 mg/m2/day for pre-cycle (days 1-5) and 3000 mg/m2 on days 1 and 4 weekly for 3 weeks (28 day cycle). The 5th and 6th patient experienced a DLT. The 3rd cohort was initiated at 600 mg/m2 pre-cycle and 3000 mg/m2 weekly with no other DLTs observed. Results: To-date, 14 patients have been enrolled in the study. The MTD was determined at 600 mg/m2/day pre-cycle and 3000 mg/m2 as per schedule. Once the MTD was determined, the cohort was expanded and, 8 patients have been treated at the MTD with no DLTs observed. Two additional patients are planned to be enrolled at this dose prior to trial completion. Of these 8 patients, 3 are still alive with 1 having prolonged survival (15 months) and the other 2 still on treatment. The most commonly observed toxicities were mild, such as anemia, anorexia, dehydration, fatigue, nausea and thrombocytopenia. Conclusions: Treatment with CPI-613 was well tolerated by patients with heavy tumor burden and refractory disease. CPI-613 has recently been shown to be well tolerated in combination with FOLFIRINOX in pancreatic cancer patients. Due to the low toxicity of CPI-613 in this study, even among highly symptomatic patients, it is anticipated that combination with other active agents is feasible in patients with advanced bile duct cancer. CPI-613 represents a novel treatment that could prove to be an exciting therapeutic alternative for patients with previously limited options and poor survival. Clinical trial information: NCT01766219.
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