MIT-001 for Prevention of CCRT-Induced OM in HNSCC Patients (MIT-001)

A Phase 2, Randomized, Double-Blind, Placebo Controlled Trial to Evaluate the Safety and Efficacy of MIT-001 in Prevention of Oral Mucositis in Patients Receiving CCRT for Locally Advanced HNSCC

The proposed study in patients with previously untreated locally advanced head and neck squamous cell carcinoma (HNSCC) is designed to evaluate the efficacy and safety of three different doses of MIT-001 compared to the placebo in prevention of oral mucositis (OM) in patients with HNSCC who are undergoing concurrent chemoradiotherapy (CCRT).

Study Overview

• Status: Active, not recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma; Oral Mucositis
• Intervention / Treatment: Drug: MIT-001 plus CCRT

Detailed Description

Oral mucositis associated with cancer therapy carries a significant morbidity. OM is a common complication in patients receiving CCRT used for treating HNSCC. Mucositis lesions can be painful, affect nutrition and quality of life (QoL), and have a significant economic impact. However, a definitive intervention regime has not been established. Therefore, it is essential to develop appropriate treatment.

MitoImmune Therapeutics Inc. (hereafter referred to as Sponsor) has developed MIT-001 which can scavenge abnormal levels of reactive oxygen species (ROS), enabling the cells to retain mitochondrial membrane permeability and mitochondrial function. This eventually inhibits additional ROS production, indicating that MIT-001 can prevent excessive inflammation caused by ROS. In addition, MIT-001 may possibly 1) block inflammatory cytokine production via inhibiting nuclear factor kappa B (NF kB) or inflammasome dependent pathways, 2) inhibit necrosis/necroptosis via blocking high mobility group box 1 (HMGB1) mediated cytokine production, and 3) balance regulation between T helper type 1/17 (Th1/17) and regulatory T cells.

Based on the pathophysiological progression of CCRT-associated OM, initiated by direct injury to basal epithelial cells which experience deoxyribonucleic acid (DNA) damage and increased ROS levels, Sponsor expects the prevention of OM in patients receiving CCRT of locally advanced HNSCC with MIT 001 by effectively scavenging increased ROS induced by CCRT.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daegu, Korea, Republic of
    • Keimyung University Dongsan Hospital
  • Daejeon, Korea, Republic of
    • Chungnam National University Hospital
  • Goyang-si, Korea, Republic of
    • National Cancer Center
  • Gyeonggi-do, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Incheon, Korea, Republic of
    • Inha University Hospital
  • Seoul, Korea, Republic of, 08308
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of
    • Hanyang University Seoul Hospital
  • Seoul, Korea, Republic of, 03082
    • Seoul National University Hospital
  • Gyeonggi-do
    • Suwon, Gyeonggi-do, Korea, Republic of, 16247
      • The Catholic University of Korea Saint Vincent's Hospital
  • Jeollabuk-do
    • Jeonju, Jeollabuk-do, Korea, Republic of, 54907
      • Jeonbuk National University Hospital
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
  • California
    • Los Angeles, California, United States, 90033
      • Norris Comprehensive Cancer Center
  • Kansas
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas
  • New York
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Wake Forest Baptist Health - Comprehensive Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • James Cancer Hospital Solove Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed HNSCC (The American joint committee on cancer [AJCC] 8th edition, Stage II, III, IVA, or IVB), involving either the oral cavity or oropharynx, or HPV-positive Stage I oropharyngeal cancer.
• Treatment plan to receive a continuous course of intensity-modulated radiation therapy (IMRT) for definitive treatment of HNSCC delivered as single daily fractions of 1.8 to 2.5 Gy with a cumulative radiation dose between 60 and 72 Gy (EQD2 of 60 to 72 Gy, α/β ratio=10): Planned radiation treatment fields must include at least 30% of oral cavity that are planned to receive a total of 50 Gy or higher.
• CCRT plan to receive standard cisplatin monotherapy: Standard cisplatin monotherapy administered weekly (30 to 40 mg/m2), once per week for 5 to 7 continuous weeks.
• Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 1 or less
• Serum pregnancy test negative for women of childbearing potential (woman of childbearing potential [WOCBP]

Exclusion Criteria:

• Patients who have active mucositis at screening.
• Planned to receive Erbitux™ (Cetuximab) or other targeted or immune therapy during the study.
• Tumor of the lips, sinuses, or salivary glands or unknown primary tumors.
• Metastatic disease (M1) Stage.
• Known history of severe vascular toxicity or allergies or intolerance to cisplatin and similar platinum-containing compounds.
• Any clinically significant and/or active infection, other systemic illness or condition (other than HNSCC) that would preclude them from participating in the study in the opinion of the Investigator.
• Prior resective surgery (4 weeks or less than 4 weeks from receiving surgery to randomization) for primary tumor under treatment for HNSCC.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching placebo	Drug: MIT-001 plus CCRT; MIT-001 IV-infusion plus CCRT
Experimental: 20 mg; MIT-001 20 mg	Drug: MIT-001 plus CCRT; MIT-001 IV-infusion plus CCRT
Experimental: 40 mg; MIT-001 40 mg	Drug: MIT-001 plus CCRT; MIT-001 IV-infusion plus CCRT
Experimental: 60 mg; MIT-001 60 mg	Drug: MIT-001 plus CCRT; MIT-001 IV-infusion plus CCRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of severe OM	severe OM (WHO criteria Grade 3 or higher) at a cumulative radiation dose of 60 Gy	From first treatment to 2 months of safety follow-up period after CCRT completion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of OM	Incidence of OM of each Grade (WHO criteria)	From first treatment to 2 months of short-term safety follow-up period after CCRT completion
Time to onset of severe OM	Time to onset of severe OM, defined as Grade 3 or higher (WHO criteria)	From first treatment to 2 months of short-term safety follow-up period after CCRT completion
Mouth pain and discomfort	Patient-reported mucositis-related mouth pain and discomfort	From first treatment to 2 months of short-term safety follow-up period after CCRT completion
Analgesic use for OM	Frequency and Cumulative dose (in morphine mg equivalent)	From first treatment to 2 months of short-term safety follow-up period after CCRT completion

Collaborators and Investigators

• Sponsor: MitoImmune Therapeutics
• Investigators: Study Director: Jinsang Jung, M.Pharm, MitoImmune Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2021
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: November 26, 2020
• First Submitted That Met QC Criteria: November 26, 2020
• First Posted (Actual): December 3, 2020

Study Record Updates

• Last Update Posted (Actual): April 6, 2025
• Last Update Submitted That Met QC Criteria: April 3, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Oral Mucositis; MIT-001; OM; NecroX-7; CCRT-associated OM; CCRT-induced OM; Mitochondria-targeted; ROS scavenger
• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Gastroenteritis; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Mucositis; Stomatitis
• Other Study ID Numbers: MIT001-OM-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No