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

BMJ Open. 2016 Jun 24;6(6):e010696. doi: 10.1136/bmjopen-2015-010696.

Abstract

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 ≥18 years 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 15 mg, respectively. Calculated MTD of idarubicin was 10 mg. At the 10 mg idarubicin dose, patients presented a longer TTD than at 5 mg, 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 41 days (21 to NA) at 5 mg, 23 days (20 to NA) at 10 mg and 25 days (17 to NA) at 15 mg. These results show the importance of studying HRQoL in phase I trials.

Trial registration number: NCT01040559; Post-results.

Keywords: Health-related Quality of Life; longitudinal analysis; oncology clinical trial; phase I; time to deterioration.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / adverse effects
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / mortality
  • Chemoembolization, Therapeutic*
  • Disease-Free Survival
  • Fatigue / chemically induced
  • Female
  • Humans
  • Idarubicin / administration & dosage*
  • Idarubicin / adverse effects
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / mortality
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Pain / chemically induced
  • Quality of Life*

Substances

  • Antibiotics, Antineoplastic
  • Idarubicin

Associated data

  • ClinicalTrials.gov/NCT01040559