Patient’s Death Halts Cancer Drug Trial
Breast cancer patient succumbs to liver failure after investigational treatment (November 6)
A phase I study of an investigational oral inhibitor of apoptosis (IAP) antagonist, CUDC-427, has been placed on partial clinical hold by the FDA following the death of a patient who had progressed to liver failure approximately 1 month after the discontinuation of CUDC-427 dosing.
Under this partial clinical hold, new patients may not be enrolled in the study until the drug’s developer (Curis, Inc.) provides the FDA with requested additional data and an analysis of patients treated with CUDC-427, and until a proposed protocol amendment is submitted to and accepted by the FDA.
The current open-label, single-agent, dose-escalation phase I study of CUDC-427 was initiated in the third quarter of 2013 in patients with advanced or refractory solid tumors or lymphomas. The study was designed to determine the maximum tolerated dose (MTD) and recommended single-agent phase II dose of CUDC-427 using a continuous, twice-daily treatment schedule.
One patient with breast cancer metastatic to the liver, lungs, bone, and ovaries developed serious adverse events related to liver function, including increased serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymes and bilirubin. Unlike prior clinical experience with CUDC-427, this patient’s liver enzyme levels did not recover in response to CUDC-427 discontinuation, and the patient died of liver failure approximately 1 month after the discontinuation of CUDC-427 dosing.
No patients are currently being treated with CUDC-427 in this study, as all other patients have discontinued dosing because of disease progression or patient or physician discretion during the course of the study.
Curis licensed CUDC-427 from Genentech, which had completed a 42-patient phase I trial in 2012. No MTD was determined in that study, in which CUDC-427 was administered once daily for 2 weeks, followed by 1 week off treatment.
Source: Curis, Inc.; November 6, 2013.