EC-18 for Oral Mucositis in Patients With Concomitant Chemoirradiation

This is a Phase 2, randomized, double-blind, placebo-controlled, 2-stage trial in subjects with squamous cell cancers of the mouth, oropharynx, hypopharynx and nasopharynx planned to receive standard fractionated IMRT-delivered radiotherapy with concomitant chemotherapy (cisplatin). Informed consent will be obtained from each subject prior to enrollment.

The trial will be performed in 2 stages:

Stage 1 will consist of a blinded parallel group safety study of 4 cohorts in which 24 subjects will be randomized (1:1:1:1) into four equally sized groups to receive one of three doses of EC-18 (500 mg, 1000 mg, 2000 mg; unit dose of 500 mg) or placebo delivered in the following daily schedule:

TDD AM PM Placebo 2 placebo 2 placebo 500mg 1 active + 1 placebo 2 placebo 1000mg 1 active + 1 placebo 1 active + 1 placebo 2000mg 2 active 2 active Dosing will commence on the first day of radiation (one hour after the first fraction) and continue until the last day of radiation. Test drug will be administered as an oral 500 mg capsule in divided daily doses as indicated above. At the completion of 4 weeks of dosing, an independent Data Safety Monitoring Board (DSMB) will evaluate safety endpoints in blinded fashion. If no safety issues are identified, the DSMB will approve continuation of dosing until the last day of radiation. If a safety issue is noted, the DSMB may unblind the treatment assignment to ascertain if the adverse event is associated with study drug. DSMB assessment will be repeated after completion of dosing (when each subject has been dosed through the last day of radiation). If no safety issues are identified, the efficacy component of the study (Stage 2) will commence using the highest dose of study drug consistent with a positive safety outcome.

Stage 2 of the study will evaluate both safety and efficacy. Eighty (80) subjects will be randomized in a 1:1 scheme to receive either placebo or 2000 mg of EC-18 as determined by iDSMB in Stage 1. Twice daily dosing will begin on the first day of radiation (1 hour after the first fraction) and continue until the last day of radiation (approximately 7 weeks).

The study will be performed in four phases: screening, the active dosing phase, short-term follow-up and long-term follow-up. The screening phase will be performed within 4 weeks of randomization and will determine subjects' eligibility. The active phase will begin on the first day of study drug dosing (also the first day of radiation therapy) and will continue until the last day of radiation therapy. This period typically is 7 weeks depending on the subject's radiation plan. The short-term follow-up phase will begin on the last day of radiation and continue for approximately 4-6 weeks until clinical and symptomatic signs of oral mucositis have resolved. The long-term follow-up phase extends for 12 months following the last dose of radiation and is included to assure that EC-18 does not the impact of tumor response to treatment.