First-in-Human Expanded Cohort Study of Intrapleural Administration of TolueneSulfonamide in Patients With Malignant Pleural Effusion
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 105
- 试验地点
- 1
- 主要终点
- Objective Response Rate
研究概览
简要总结
This study aims to evaluate the safety of intrapleural injection of TolueneSulfonamide in patients with malignant pleural effusion and to explore its potential effectiveness.
详细描述
This study is a first-in-human (FIM) expansion cohort study designed to evaluate the safety and clinical activity of intrapleural injection of PTS in patients with malignant pleural effusion (MPE). Patients with MPE will be prospectively enrolled, and the study will be conducted in two parts: a safety and dose-exploration phase of intrapleural PTS administration (Part 1, P1), followed by an efficacy evaluation phase of intrapleural PTS for the treatment of MPE (Part 2, P2). Part 2 will be initiated after the safety of PTS has been established in Part 1.
Part 1 is designed as a prospective, single-arm, open-label study. Part 2 is designed as a prospective, multicenter, double-blind, randomized controlled trial with two groups: an experimental group and a control group. The experimental group will receive catheter drainage plus intrapleural PTS injection, while the control group will receive catheter drainage plus intrapleural normal saline injection.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 18 and 75 years (inclusive) at the time of signing the informed consent form.
- •Histologically or cytologically confirmed malignant pleural effusion, with the primary tumor diagnosed as non-small cell lung cancer (NSCLC).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, with an expected survival of at least 3 months.
- •Presence of dyspnea symptoms.
- •No prior local thoracic treatment within 1 month before enrollment, including intrapleural drug administration or thoracic radiotherapy (diagnostic thoracentesis is permitted).
- •Except for the subject's current stable systemic anti-tumor therapy, any other ongoing tumor-related treatments must be suspended or discontinued after evaluation by the investigator to ensure they do not interfere with the assessment of PTS treatment.
- •Fully understands the study objectives and procedures, agrees to participate in the study, and provides written informed consent.
排除标准
- •History of allergy or hypersensitivity to PTS or any of its excipients.
- •Presence of uncontrolled intrapleural infection or severe loculated pleural effusion that is difficult to manage.
- •Participation in another interventional clinical study within 3 months prior to enrollment (diagnostic studies are excluded).
- •Severe organ dysfunction, including but not limited to coagulation disorders, congestive heart failure, malignant arrhythmias, coronary artery disease requiring long-term medication, valvular heart disease, myocardial infarction, or refractory hypertension; severe cardiac, hepatic, or renal insufficiency, or active bleeding or thrombotic risk.
- •Presence of uncontrolled infectious wounds.
- •Pregnant or breastfeeding women.
- •Any other condition that, in the investigator's judgment, makes the subject unsuitable for participation in this study.
- •Criteria for withdrawal from the study.
研究组 & 干预措施
Intrapleural PTS injection plus catheter drainage group
PTS Administration (One Treatment Cycle):
One treatment cycle is defined as one week. PTS is administered three times per week on Days 1, 3, and 5. Prior to each administration, pleural effusion is drained as completely as possible until no further fluid can be obtained. The study drug is then administered via the indwelling drainage catheter, followed by an additional flush of 20 mL of normal saline. The drainage catheter is clamped for at least 24 hours after administration.
After each injection, patients are instructed to maintain prone, lateral, and supine positions for approximately 30 minutes each to facilitate even distribution of the drug within the pleural cavity. During the same treatment cycle, the drainage catheter remains clamped until the next scheduled administration. After completion of treatment, catheter drainage and standard care are continued.
干预措施: Intrapleural administration of TolueneSulfonamide (Drug)
catheter drainage alone group
Normal Saline Administration (One Treatment Cycle):
One treatment cycle is defined as one week. Normal saline is administered three times per week on Days 1, 3, and 5. Prior to each administration, pleural effusion is drained as completely as possible until no further fluid can be obtained. Normal saline is then administered via the indwelling drainage catheter, followed by an additional flush of 20 mL of normal saline. The drainage catheter is clamped for at least 24 hours after administration.
After each administration, patients are instructed to maintain prone, lateral, and supine positions for approximately 30 minutes each. During the same treatment cycle, the drainage catheter remains clamped until the next scheduled administration. After completion of treatment, catheter drainage and standard care are continued.
干预措施: Intrapleural administration of normal saline injection (Drug)
结局指标
主要结局
Objective Response Rate
时间窗: 4 weeks, 12 weeks, 6 months, and 12 months after treatment completion
Objective Response Rate (ORR) is defined as the proportion of patients achieving complete response (CR) or partial response (PR) among all enrolled patients, calculated as (CR + PR) / total number of patients × 100%, based on WHO criteria and assessed by imaging methods (ultrasound or computed tomography).
次要结局
- Percentage Change in Pleural Effusion Volume(Baseline; after one treatment cycle (each cycle is 7 days); and at 4 weeks, 12 weeks, 6 months, and 12 months of follow-up)
- Overall Survival (OS)(through study completion, an average of 1 year)
- mMRC Dyspnea Score(At baseline, after one treatment cycle (each cycle is 7 days), and at 4 weeks, 12 weeks, 6 months, and 12 months during follow-up)
- Quality of Life score(At baseline, after one treatment cycle (each cycle is 7 days), and at 4 weeks, 12 weeks, 6 months, and 12 months during follow-up)
- Incidence of Grade ≥3 treatment-emergent adverse events(through study completion, an average of 1 year)
研究者
Gang Hou
Chief Physician
China-Japan Friendship Hospital