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

Head and Neck Squamous Cell Carcinoma Clinical Trial

— MIT-001  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04651634
• Other study ID #: MIT001-OM-01
• Status: Recruiting
• Phase: Phase 2
• Start date: June 21, 2021
• Est. completion date: December 30, 2024

Study information

• Verified date: April 2023
• Source: MitoImmune Therapeutics
• Contact: Jinsang Jung
• Phone: +82 2 6933 6727
• Email: jinsang.jung[@]mitoimmune.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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, a/ß 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.

Related Conditions & MeSH terms

• Head and Neck Squamous Cell Carcinoma
• Mucositis
• Oral Mucositis
• Squamous Cell Carcinoma of Head and Neck
• Stomatitis

Intervention

Drug:
• MIT-001 plus CCRT
MIT-001 IV-infusion plus CCRT

Locations

Country	Name	City	State
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Seoul National University Bundang Hospital	Gyeonggi-do
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Jeonbuk National University Hospital	Jeonju	Jeollabuk-do
Korea, Republic of	Hanyang University Seoul Hospital	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	The Catholic University of Korea Saint Vincent's Hospital	Suwon	Gyeonggi-do
United States	James Cancer Hospital Solove Research Institute	Columbus	Ohio
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Norris Comprehensive Cancer Center	Los Angeles	California
United States	University of Pittsburgh Medical Center - Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	James P. Wilmot Cancer Center	Rochester	New York
United States	Washington University School of Medicine Siteman Cancer Center	Saint Peters	Missouri
United States	Cancer Center of Kansas	Wichita	Kansas
United States	Wake Forest Baptist Health - Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
MitoImmune Therapeutics

Countries where clinical trial is conducted

United States,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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