Clinical trial NCT04651634: MIT-001 for Prevention of CCRT-Induced OM in HNSCC Patients
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Head and Neck Squamous Cell Carcinoma
Oral Mucositis
Keywords: MIT-001
Oral Mucositis
OM
NecroX-7
CCRT-associated OM
CCRT-induced OM
Mitochondria-targeted
ROS scavenger
Lead sponsor: MitoImmune Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-12-03
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The three active treatment groups will receive either 20, 40, and 60 mg/day of MIT-001 IV infusion for 30 minutes, two times per week for 5 to 7 continuous weeks until a cumulative radiation dose of between 60 and 72 Gy, with CCRT. Placebo group will receive placebo, manufactured with the same properties and appearance as MIT 001, at same treatment frequency as MIT-001 with CCRT.
Primary purpose: SUPPORTIVE_CARE

Brief 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of severe OM
timeFrame: From first treatment to 2 months of safety follow-up period after CCRT completion
Secondary outcomes:
measure: Incidence of OM
timeFrame: From first treatment to 2 months of short-term safety follow-up period after CCRT completion
measure: Time to onset of severe OM
timeFrame: From first treatment to 2 months of short-term safety follow-up period after CCRT completion
measure: Mouth pain and discomfort
timeFrame: From first treatment to 2 months of short-term safety follow-up period after CCRT completion
measure: Analgesic use for OM
timeFrame: From first treatment to 2 months of short-term safety follow-up period after CCRT completion
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Los Angeles
country: United States
facility: Norris Comprehensive Cancer Center
state: California
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health - Comprehensive Cancer Center
state: North Carolina
city: Columbus
country: United States
facility: James Cancer Hospital Solove Research Institute
state: Ohio
city: Suwon
country: Korea, Republic of
facility: The Catholic University of Korea Saint Vincent's Hospital
state: Gyeonggi-do
city: Jeonju
country: Korea, Republic of
facility: Jeonbuk National University Hospital
state: Jeollabuk-do
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: Hanyang University Seoul Hospital
Study officials:
affiliation: MitoImmune Therapeutics
name: Jinsang Jung, M.Pharm
role: STUDY_DIRECTOR
References: