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

MitoImmune Therapeutics

Status and phase: Enrolling; Phase 2

Conditions: Oral Mucositis; Head and Neck Squamous Cell Carcinoma

Treatments: Drug: MIT-001 plus CCRT

Study type: Interventional

Funder types: Industry

Identifiers

NCT04651634

MIT001-OM-01

Details and patient eligibility

About

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).

Full 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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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60 participants in 4 patient groups, including a placebo group

20 mg

Experimental group

Description:

MIT-001 20 mg

Treatment:

Drug: MIT-001 plus CCRT

40 mg

Experimental group

Description:

MIT-001 40 mg

Treatment:

Drug: MIT-001 plus CCRT

60 mg

Experimental group

Description:

MIT-001 60 mg

Treatment:

Drug: MIT-001 plus CCRT

Placebo

Placebo Comparator group

Description:

Matching placebo

Treatment:

Drug: MIT-001 plus CCRT