Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate EC-18 for Oral Mucositis in Patients With Concomitant Chemoirradiation for Cancers of the Mouth, Oropharynx, Hypopharynx and Nasopharynx

EC-18-202

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. Stage 2 of the study will evaluate both safety and efficacy. Stage 2 will consist of eighty (80) subjects who 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.

2018-07-03

2021-05-14

2021-05-14

Completed

Early phase I

105

Inclusion Criteria: * Signed informed consent * Male or female age 18 years or older * Pathologically confirmed diagnosis of squamous cell carcinoma of the mouth, oropharynx, hypopharynx or nasopharynx * Planned to receive IMRT with daily fractions of 2.0 Gy to 2.2 Gy to a cumulative dose of at least 60 Gy and a maximum of 72 Gy * Radiation fields to include at least two mucositis sites at risk (buccal mucosa, floor of mouth, ventral and lateral tongue, soft palate) in which both sites receive a minimum cumulative dose of 55 Gy * Planned to receive concomitant single agent chemotherapy with cisplatin given either weekly or tri-weekly * Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 * Screening Laboratory Values Hemoglobin ≥ 9g/dL White blood cell count ≥ 3,500 cells/mm3 Absolute neutrophil count ≥ 1,500 cells/mm3 Total bilirubin ≤ 2 times upper limit of normal Serum AST and ALT ≤ 2.5 times upper limit of normal Serum creatinine concentration ≤ 2mg/mL Pregnancy test: negative for females of childbearing potential * Subjects of childbearing potential must consent to utilize a medically accepted means of contraception throughout the active dosing period with study medication and for a minimum of 30 days following the administration of the last dose of study medication. Exclusion Criteria: * Unable to provide informed consent or, in the opinion of the Principal Investigator, comply with the protocol. * Prior radiation therapy to the head and neck * Metastatic disease * Presence of active infectious disease excluding oral candidiasis * Presence of oral mucositis or any oral lesion that would confound the assessment of oral mucositis * Active systemic disease or condition known to impact the risk or course of oral mucositis including chronic immunosuppression and known seropositivity for HIV * Use of any investigational agent within 30 days of the first radiation dose * Active alcohol abuse syndrome * Subjects with a history of hepatitis of any etiology or hepatic insufficiency * Pregnant or nursing at the time of signing informed consent * Known sensitivity to any study medication * Unwilling or unable to complete study diary * Any other condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with the protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': '2 stages: Stage 1 is a blinded parallel group safety study of 4 cohorts of 24 subjects randomized (1:1:1:1) to receive either EC-18 500 mg, 1000 mg, 2000 mg, or placebo.\n\nDosing will commence on the first day of radiation and continue until the last day of radiation. After of 4 weeks, an independent Data Safety Monitoring Board (DSMB) will evaluate safety endpoints in blinded fashion. DSMB assessment will be repeated after completion of dosing. Stage 2 of the study will evaluate both safety and efficacy.\n\nEighty (80) subjects will be randomized in a 1:1 scheme to receive placebo or EC-18 at the dose determined in Stage 1. The design of stage 2 is the same as stage 1.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'DOUBLE', 'maskingDescription': 'Subjects and investigators will be blinded to treatment assignments', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 105, 'type': 'ACTUAL'}}

2023-07-27