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EC-18 for Oral Mucositis in Patients With Concomitant Chemoirradiation

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ClinicalTrials.gov Identifier: NCT03200340
Recruitment Status : Recruiting
First Posted : June 27, 2017
Last Update Posted : July 19, 2019
Sponsor:
Information provided by (Responsible Party):
Enzychem Lifesciences Corporation

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.

Eighty (80) subjects will be randomized in a 1:1 scheme to receive either placebo or EC-18 at the dose determined in Stage 1.


Condition or disease Intervention/treatment Phase
Stomatitis Drug: EC-18 Drug: Placebo Phase 2

Detailed Description:

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 EC-18 at the dose determined in Stage 1. Twice daily dosing (assuming EC-18 dose is greater than 500 mg) 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 104 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

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.

Masking: Double (Participant, Investigator)
Masking Description: Subjects and investigators will be blinded to treatment assignments
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : January 1, 2018
Estimated Primary Completion Date : June 20, 2020
Estimated Study Completion Date : June 20, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
Matching placebo
Drug: EC-18
Oral administration of EC-18 twice daily
Other Name: EC-18 soft capsules

Drug: Placebo
Placebo to match EC-18 capsule administration
Other Name: Placebo capsule

Experimental: EC-18 500 mg
1 capsule of EC-18
Drug: EC-18
Oral administration of EC-18 twice daily
Other Name: EC-18 soft capsules

Drug: Placebo
Placebo to match EC-18 capsule administration
Other Name: Placebo capsule

Experimental: EC-18 1000 mg
2 capsules of EC-18 500 mg
Drug: EC-18
Oral administration of EC-18 twice daily
Other Name: EC-18 soft capsules

Drug: Placebo
Placebo to match EC-18 capsule administration
Other Name: Placebo capsule

Experimental: EC-18 2000 mg
4 capsules of EC-18 500 mg
Drug: EC-18
Oral administration of EC-18 twice daily
Other Name: EC-18 soft capsules

Drug: Placebo
Placebo to match EC-18 capsule administration
Other Name: Placebo capsule




Primary Outcome Measures :
  1. Duration of Severe Oral Mucositis [ Time Frame: 7 weeks ]
    Duration of Grade 3 or 4 oral mucositis


Secondary Outcome Measures :
  1. Incidence of severe oral mucositis defined as WHO grades 3 or 4 during the active treatment period [ Time Frame: 7 weeks ]
    Incidence of severe oral mucositis defined as WHO grades 3 or 4 over the 7-week active treatment period

  2. Incidence of ulcerative mucositis (defined as WHO grades 2,3,4) during the active treatment period [ Time Frame: 7 weeks ]
    Incidence of grade 3 or 4 ulcerative mucositis

  3. Duration of ulcerative mucositis (WHO criteria) [ Time Frame: 7 weeks ]
    Duration of grade 3 or 4 ulcerative mucositis

  4. Delay in onset of severe oral mucositis (WHO criteria) [ Time Frame: 7 weeks ]
    Time to onset of grade 3 or 4 severe oral mucositis

  5. Reduction in subject-reported mucositis-related mouth pain and analgesic use [ Time Frame: 7 weeks ]
    Frequency of disease-related mouth pain and analgesic use


Other Outcome Measures:
  1. Incidence of severe oral mucositis as defined by NCI-CTC v.4 criteria [ Time Frame: 7 weeks ]
    Incidence of severe oral mucositis based on NCI-CTC v.4 criteria

  2. Duration of severe oral mucositis as defined by NCI-CTC v.4 [ Time Frame: 7 weeks ]
    Duration of severe oral mucositis based on NCI-CTC v.4 criteria

  3. Healthcare resource use including reliance on gastrostomy feeding, unplanned office visits, emergency room visits, and hospitalizations [ Time Frame: 7 weeks ]
    Healthcare resource utilization

  4. Breaks in radiation delivery [ Time Frame: 7 weeks ]
    Frequency of interruptions in radiation therapy

  5. Genomic differences between responders and non-responders [ Time Frame: 7 weeks ]
    Subset of subjects who consent to assess genomics

  6. Incidence of severe oral mucositis as defined by Radiation Therapy [ Time Frame: 7 weeks ]
    Incidence of severe oral mucositis based on NCI-CTC v.4 and RTOG criteria

  7. Duration of severe oral mucositis as defined by RTOG criteria [ Time Frame: 7 weeks ]
    Duration of severe oral mucositis based on RTOG criteria

  8. Break duration in radiation delivery [ Time Frame: 7 weeks ]
    Duration of interruptions in radiation therapy



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03200340


Contacts
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Contact: Marina Zis, MD 1-425-260-3378 marina.zis@enzychem.com
Contact: John Choi, MS 1-210-408-5488 jhchoi@enzychem.com

Locations
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United States, Arkansas
NEA Baptist Cancer Center Recruiting
Jonesboro, Arkansas, United States, 72401
Contact: Emily Carvel         
United States, California
Veterans Affairs Long Beach Health Care System Recruiting
Long Beach, California, United States, 90822
Contact: Thao Nguyen         
United States, Georgia
Winship Cancer Institute of Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Swathi Chinarangari         
United States, Illinois
NorthShore University HealthSystem Recruiting
Evanston, Illinois, United States, 60201
Contact: Michelle Britto         
Southern Illinois University School of Medicine Recruiting
Springfield, Illinois, United States, 62702
Contact: Kathy Robinson         
United States, Kansas
Cancer Center of Kansas Recruiting
Wichita, Kansas, United States, 67214
Contact: Pat Stone         
United States, Kentucky
University of Kentucky, Chandler Medical Center, CCTS Recruiting
Lexington, Kentucky, United States, 40536
Contact: Linda Rice         
United States, Maryland
Greater Baltimore Medical Center Recruiting
Baltimore, Maryland, United States, 21204
Contact: Melissa Loomis         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110-1010
Contact: Josh Smith         
United States, Oklahoma
University of Oklahoma Health Sciences Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Deanna Barnett         
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239
Contact: John Minger         
VA Portland HealthCare System Recruiting
Portland, Oregon, United States, 97239
Contact: Tahnee Groat         
United States, Pennsylvania
St. Luke's Cancer Center - Anderson Campus Recruiting
Easton, Pennsylvania, United States, 18045
Contact: Jillian Timer         
United States, Texas
UT Southwestern Harold C. Simmons Comprehensive Cancer Center Recruiting
Dallas, Texas, United States, 75390
Contact: Tammy Lightfoot         
Hope Cancer Center of East Texas Recruiting
Tyler, Texas, United States, 75701
Contact: Grace Loredo         
Baylor Scott & White Medical Center - Hillcrest Recruiting
Waco, Texas, United States, 76712
Contact: Dedra Preece         
Sponsors and Collaborators
Enzychem Lifesciences Corporation
Investigators
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Principal Investigator: Dong Moon Shin, MD Emory University Winship Cancer Institute
Principal Investigator: Mahesh Kudrimoti, MD University of Kentucky, Chandler Medical Center, CCTS

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Responsible Party: Enzychem Lifesciences Corporation
ClinicalTrials.gov Identifier: NCT03200340     History of Changes
Other Study ID Numbers: EC-18-202
First Posted: June 27, 2017    Key Record Dates
Last Update Posted: July 19, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Mucositis
Stomatitis
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Mouth Diseases
Stomatognathic Diseases