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
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 60
- 试验地点
- 16
- 主要终点
- Incidence of severe OM
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This study design will minimize bias and provide reference data (i.e., data from placebo treated subjects) which will aid in the interpretation of results. To limit the occurrence of conscious and unconscious bias in the conduct and interpretation of safety and efficacy results, the study is double blind where the subject, the Investigators/site staff, and the Sponsor staff remain unaware of the treatment assignment. The planned safety assessments that will be performed during the study are considered acceptable measures for ensuring the safety of subjects during a clinical study.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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]
排除标准
- •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.
研究组 & 干预措施
20 mg
MIT-001 20 mg
干预措施: MIT-001 plus CCRT (Drug)
40 mg
MIT-001 40 mg
干预措施: MIT-001 plus CCRT (Drug)
60 mg
MIT-001 60 mg
干预措施: MIT-001 plus CCRT (Drug)
Placebo
Matching placebo
干预措施: MIT-001 plus CCRT (Drug)
结局指标
主要结局
Incidence of severe OM
时间窗: From first treatment to 2 months of safety follow-up period after CCRT completion
severe OM (WHO criteria Grade 3 or higher) at a cumulative radiation dose of 60 Gy
次要结局
- Mouth pain and discomfort(From first treatment to 2 months of short-term safety follow-up period after CCRT completion)
- Analgesic use for OM(From first treatment to 2 months of short-term safety follow-up period after CCRT completion)
- Incidence of OM(From first treatment to 2 months of short-term safety follow-up period after CCRT completion)
- Time to onset of severe OM(From first treatment to 2 months of short-term safety follow-up period after CCRT completion)