An explorative study to assess the association between health-related quality of life and the recommended phase II dose in a phase I trial: idarubicin-loaded beads for chemoembolisation of hepatocellular carcinoma

Objectives The objective of this study was to explore the association between health-related quality of life (HRQoL) and the recommended phase 2 dose in a phase I clinical trial according to the Time to HRQoL deterioration approach (TTD). Setting This is a phase I dose-escalation trial of transarterial chemoembolisation (TACE) with idarubicin-loaded beads performed in cirrhotic patients with hepatocellular carcinoma. Patients had to complete the EORTC QLQ-C30 HRQoL questionnaire at baseline and at days 15, 30 and 60 after TACE. Participants Patients aged 18years with HCC unsuitable for curative treatments were evaluated for the study (N=21). Primary and secondary outcome measurements The primary objective was to determine the maximum tolerated dose (MTD) of idarubicin loaded after a single TACE session. MTD was defined as the dose level closest to that causing dose-limiting toxicity in 20% of patients. HRQoL was the secondary end point. Results Between March 2010 and March 2011, 9, 6 and 6 patients were included at idarubicin dose levels of 5, 10 and 15mg, respectively. Calculated MTD of idarubicin was 10mg. At the 10mg idarubicin dose, patients presented a longer TTD than at 5mg, for global health status (HR=0.91 (95% CI 0.18 to 4.72)), physical functioning (HR=0.38 (0.04 to 3.22)), fatigue (HR=0.67 (0.18 to 2.56)) and pain (HR=0.47 (0.05 to 4.24)). Conclusions These HRQoL results were consistent with the estimated MTD, with a median TTD for global health status of 41days (21 to NA) at 5mg, 23days (20 to NA) at 10mg and 25days (17 to NA) at 15mg. These results show the importance of studying HRQoL in phase I trials. Trial registration number NCT01040559; Post-results.