Abstract 5093
Background
Oral drug formulations have several advantages compared to intravenous formulation. Apart from patient convenience and favorable pharmaco-economics they offer the possibility of frequent drug administration at home. In this study, we present a new oral irinotecan formulation designed as an enteric coated immediate release tablet which in pre-clinical studies has shown good exposure with low variability.
Methods
A phase I, dose escalating study to assess safety, tolerability, pharmacokinetics and efficacy of an oral irinotecan formulation and to establish the maximum tolerated dose (MTD). Each treatment cycle was once-daily irinotecan for 14 days followed by one week rest.
Results
25 patients were included across four cohorts; 3 patients were included in cohort 1 (20 mg/m²), 7 patients were included in cohort 2 (30 mg/m²), 3 patients were included in cohort 3 (25 mg/m²) and 12 patients were included in cohort 4 (21 mg/m²). Median age was 67 years, 52% were performance status (PS) 0 while 48% were PS 1. Median number of prior therapies was 3 (range1 to 6). MTD was established at 21 mg/m². No responses were observed. Nine patients (36%) had stable disease (SD), lasting median 19 weeks (range 7-45 weeks). Among these 5 patients had previously received irinotecan.No grade 3/4 hematologic toxicities were reported. Totally 6 patients experienced grade 1/2 anemia, 3 patients had grade 1/2 leucopenia and 1 patient had grade 1 trombocytopenia. Most common non-hematological grade 1 and 2 adverse events were nausea, fatigue, diarrhea, vomiting and cholinergic syndrome. Grade 3 toxicities included diarrhea, fatigue, nausea and vomiting, no grade 4 events were reported. PK data showed consistent daily exposures during treatment at days 1 and 14 and no drug accumulation. SN-38 interpatient variability was in the same range as after infusion.
Conclusions
Oral irinotecan was generally well tolerated; side effects were manageable and similar in type to those observed with intravenous irinotecan. Hematological toxicities were few and only grade 1/2. In this heavily pre-treated patient population oral irinotecan demonstrated activity even among patients previously treated with irinotecan.
Clinical trial identification
EudraCT: 2014-005584-32; NCT03295084.
Legal entity responsible for the study
Herlev and Gentofte Hospital, Department of Oncology, Herlev, Denmark.
Funding
Oncoral Pharma ApS, Ballerup, Denmark.
Editorial Acknowledgement
Disclosure
J.A. Palshof, I. Kümler, P.G. Sørensen, B.V. Jensen, D.L. Nielsen: Oncoral Pharma ApS provided study medication.