Risk management and eligibility criteria for QTc assessment in patients with advanced cancer
Nenad Sarapa, X. Huang, Mary Laura Varterasian, Howard J. Fingert · Journal of Clinical Oncology · 2005
3047 Background: Emerging regulatory and industry practices (ICH E14, 2004) require the potential for QTc interval prolongation to be characterized in a ‘Thorough QT’ (TQT) study with eligibility restricted based on screening QTc criteria (=65 years. Distribution by gender-specific QTc risk categories showed that 94 men (87.9%) and 49 women (92.5%) had normal QTc (450 and >470 ms, respectively). No QTc was >500 ms (CTCAE Grade 3). Overall, 17 of 160 patients (10.6%) had baseline QTc above the upper limits of normal. Conclusions: These data are consistent with anecdotal reports that cancer patients may have longer QTc than other segments of the population. Over 10% of our patients would have been excluded from treatment with a promising anticancer agent if eligibility criteria from TQT studies in non-oncology populations were applied. Given risk-benefit considerations and expectations for access to new agents in clinical trials, our data support alternative approaches to eligibility criteria and risk management in studies designed to evaluate QTc prolongation in patients with advanced cancer. No significant financial relationships to disclose.