C2005-01 enrolled 45 male and female patients, and C2007-01 enrolled 35 female patients. Most patients had received prior chemotherapy (Table 1). Ovarian, breast, and lung cancers were most common (Table 2). Ovarian cancer affected 83% of women in C2007-01. More than half the patients received carboplatin-based chemotherapy, and 65% received an HEC regimen (Table 3).
(To view a larger version of Table 1, click here.)
Patient dispositions and protocol deviations
C2005-01 patients receiving MEC (22 [49%]) or HEC (23 [51%]) were enrolled at six clinical sites in the United States; 17 received APF530 250 mg, 15 received APF530 500 mg, and 13 received APF530 750 mg. Three of 15 patients in the 500 mg group did not complete the study: two had unrelated serious AEs (one dysphagia; one dyspnea, malaise, and diaphoresis) and one withdrew consent (Table 4). After completing the study, one patient experienced fever and septic shock within 4 weeks after receiving APF530 and later died of underlying non-small-cell lung cancer (NSCLC).
(To view a larger version of Table 4, click here.)
Six patients scheduled to receive chemotherapy on days 1 and 8, or on days 1, 8, and 15 were allowed to enter the study by the medical monitors, and one also had head and neck cancer. All patients who received study drug were included in the safety analysis. Four patients who did not receive the full dose of study drug were excluded from the pharmacokinetic and efficacy analyses (N=41); five patients with missing samples were also excluded from the pharmacokinetic analysis (N=36).
C2007-01 patients were randomized at three sites in Poland; 17 received APF530 250 mg, and 18 received APF530 500 mg (Table 4). Data from six patients with minor deviations from the protocol were allowed by the medical monitor: five were >65 years of age, and one had enrolled in another trial within 30 days. Twelve patients missing up to three blood samples were included in the pharmacokinetic analysis. Two patients received restricted medications, one did not receive the full oral dose of dexamethasone on two occasions, and two did not have final ECGs available for analysis. These patients were included in the final analysis, and their inclusion did not confound the study results.