Prophylaxis of recurrent chemotherapy-induced oral mucositis: A phase II multicenter, randomized, placebo-controlled trial of recombinant human intestinal trefoil factor (rhITF)

Abstract

9514 Background: Naturally occurring ITF is a peptide produced predominantly in the gastrointestinal tract, where it plays a key role in mucosal restitution. The purpose of the current Phase II study was to evaluate safety and efficacy of rhITF administered as an oral spray topically to the oral cavity of patients at high risk for developing oral mucositis (OM). Methods: Colorectal cancer patients (N=99) presenting with symptomatic OM (WHO grade ≥2) in the first cycle of chemotherapy were randomized into three groups (N=33/group) and treated with either placebo, rhITF 10mg/mL (low dose) or rhITF 80mg/mL (high dose) by oral spray (300μl, 8 times/day) for 14 consecutive days in the second chemotherapy cycle. Patients were assessed days 1, 3, 5, 7, 10, 12, 14 and 21 ± 2 for WHO grade of OM, and treatment-related effects. Results: Patient-reported compliance was >95%. rhITF oral spray was well tolerated. Treatment groups were not significantly different with respect to the development of Treatment-Emergent Signs and Symptoms (TESSs). A minority of chemotherapy patients (6/99, 6.1%) had TESSs; 4 were associated with treatment (1 placebo, 2 low dose and 1 high dose rhITF respectively). All events were mild to moderate in intensity and resolved spontaneously without sequelae. There were no serious adverse events or deaths in the study. Frequency of WHO grade ≥2 oral mucositis in the placebo, low dose rhITF and high dose rhITF groups was 48.5% (16/33), 9.1% (3/33) and 12.1% (4/33), respectively (for either low or high dose versus placebo p<0.001). Assessment of area under the curve relative to OM incidence and severity revealed a statistically significant treatment effect of rhITF versus placebo (WHO scores, p<0.01). Conclusions: rhITF oral spray formulation appears safe and well-tolerated when given concurrently with chemotherapy. Prophylactic use of rhITF at either high or low dose was associated with a significant (∼80%) reduction in OM occurrence in patients at high risk for development of the lesion. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration The GI Company Inc. ActoGenix NV, Alizyme Ther., Ltd., Endo Pharm Inc.,, Genzyme Corporation, MGI Pharma Inc., The GI Company Inc. The GI Company Inc. The GI Company Inc.