EC-18 for Oral Mucositis in Patients With Concomitant Chemoirradiation

NCT03200340 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: EC-18-202
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 20

Brief Summary

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.

Conditions

Stomatitis

Outcome Measures

Primary Outcomes (1)

• Duration of Severe Oral Mucositis (SOM) during the active treatment and short-term follow-up periods

  Duration of Grade 3 or 4 oral mucositis

  7 Weeks (Active) + 4-6 Weeks (STFU)

Secondary Outcomes (8)

• Duration of SOM during the active treatment period

  7 Weeks (Active)

• Incidence of severe oral mucositis defined as WHO grade of 3 or 4 during the active treatment period

  7 Weeks (Active)

• Incidence of severe oral mucositis defined as WHO grade of 3 or 4 during the active treatment and short-term follow-up periods

  7 Weeks (Active) + 4-6 Weeks (STFU)

• Incidence of ulcerative mucositis (defined as WHO grade of 2, 3, or 4) during the active treatment period

  7 Weeks (Active)

• Incidence of ulcerative mucositis (defined as WHO grade of 2, 3, or 4) during the active treatment and short-term follow-up periods

  7 Weeks (Active) + 4-6 Weeks (STFU)

Other Outcomes (9)

• Duration of severe oral mucositis as defined by RTOG criteria

  7 Weeks

• Incidence of severe oral mucositis as defined by RTOG criteria

  7 Weeks

• Duration of severe oral mucositis as defined by NCI-CTCAE v.4 criteria

  7 Weeks

Study Arms (6)

[Part 1] Placebo

PLACEBO COMPARATOR

Matching placebo

Drug: Placebo

[Part 1] EC-18 500 mg

EXPERIMENTAL

1 capsule of EC-18

Drug: EC-18

[Part 1] EC-18 1000 mg

EXPERIMENTAL

2 capsules of EC-18 500 mg

Drug: EC-18

[Part 1] EC-18 2000 mg

EXPERIMENTAL

4 capsules of EC-18 500 mg

Drug: EC-18

[Part 2] Placebo

PLACEBO COMPARATOR

Placebo 2000mg

Drug: Placebo

[Part 2] EC-18 2000mg

EXPERIMENTAL

RP2D: EC-18 2000mg (Part 1 result)

Drug: EC-18

Interventions

EC-18 DRUG

Oral administration of EC-18 twice daily

Also known as: EC-18 soft capsules

[Part 1] EC-18 1000 mg; [Part 1] EC-18 2000 mg; [Part 1] EC-18 500 mg; [Part 2] EC-18 2000mg

Placebo DRUG

Placebo to match EC-18 capsule administration

Also known as: Placebo capsule

[Part 1] Placebo; [Part 2] Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Enzychem Lifesciences Corporation: lead

Study Sites (20)

Veterans Affairs Long Beach Health Care System

Long Beach, California, 90822, United States

Location

UCLA Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

NorthShore University HealthSystem

Evanston, Illinois, 60201, United States

Location

Southern Illinois University School of Medicine

Springfield, Illinois, 62702, United States

Location

Cancer Center of Kansas

Wichita, Kansas, 67214, United States

Location

University of Kentucky, Chandler Medical Center, CCTS

Lexington, Kentucky, 40536, United States

Location

Greater Baltimore Medical Center

Baltimore, Maryland, 21204, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110-1010, United States

Location

Mount Sinai - Union Square

New York, New York, 10003, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

VA Portland HealthCare System

Portland, Oregon, 97239, United States

Location

St. Luke's Cancer Center - Anderson Campus

Easton, Pennsylvania, 18045, United States

Location

Hope Cancer Center of East Texas

Tyler, Texas, 75701, United States

Location

Baylor Scott & White Medical Center - Hillcrest

Waco, Texas, 76712, United States

Location

MultiCare Institute for Research and Innovation

Spokane, Washington, 98405, United States

Location

MultiCare Institute for Research and Innovation

Tacoma, Washington, 98405, United States

Location

MeSH Terms

Conditions

Stomatitis

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases

Study Officials

• Dong Moon Shin, MD

  Emory University Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

• Mahesh Kudrimoti, MD

  University of Kentucky, Chandler Medical Center, CCTS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Subjects and investigators will be blinded to treatment assignments
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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. Dosing 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. Eighty (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.

Study Record Dates

• First Submitted: June 13, 2017
• First Posted: June 27, 2017
• Study Start: July 3, 2018
• Primary Completion: May 14, 2021
• Study Completion: May 14, 2021
• Last Updated: July 27, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (20)