Malignant Pleural Effusions (Mpe), Non Small Cell Lung Cancer
Conditions
Keywords
Malignant Pleural Effusion, Para-toluenesulfonamide
Brief summary
This study aims to evaluate the safety of intrapleural injection of TolueneSulfonamide in patients with malignant pleural effusion and to explore its potential effectiveness.
Detailed description
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.
Interventions
DRUGIntrapleural administration of TolueneSulfonamide
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.
DRUGIntrapleural administration of normal saline injection
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.
Sponsors
Gang Hou
The Second Affiliated Hospital of Harbin Medical University
The Affiliated Hospital of Xuzhou Medical University
Anhui Chest Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
This study consists of two parts. Part 1 is a first-in-human study enrolling 15 patients with malignant pleural effusion (MPE) to assess the safety of intrapleural PTS. Part 2 will enroll 90 patients with MPE and, after safety is confirmed, randomize them 2:1 to receive PTS plus catheter drainage or normal saline plus catheter drainage. Treatment is given in weekly cycles with dosing on Days 1, 3, and 5. Pleural effusion is drained before each dose, followed by intrapleural administration and catheter clamping. After treatment, standard drainage and supportive care are continued.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age between 18 and 75 years (inclusive) at the time of signing the informed consent form. 2. Histologically or cytologically confirmed malignant pleural effusion, with the primary tumor diagnosed as non-small cell lung cancer (NSCLC). 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, with an expected survival of at least 3 months. 4. Presence of dyspnea symptoms. 5. No prior local thoracic treatment within 1 month before enrollment, including intrapleural drug administration or thoracic radiotherapy (diagnostic thoracentesis is permitted). 6. 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. 7. Fully understands the study objectives and procedures, agrees to participate in the study, and provides written informed consent.
Exclusion criteria
1. History of allergy or hypersensitivity to PTS or any of its excipients. 2. Presence of uncontrolled intrapleural infection or severe loculated pleural effusion that is difficult to manage. 3. Participation in another interventional clinical study within 3 months prior to enrollment (diagnostic studies are excluded). 4. 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. 5. Presence of uncontrolled infectious wounds. 6. Pregnant or breastfeeding women. 7. Any other condition that, in the investigator's judgment, makes the subject unsuitable for participation in this study. 8. Criteria for withdrawal from the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | The rate of change in pleural effusion volume is calculated as (baseline pleural effusion volume - post-treatment pleural effusion volume) / baseline pleural effusion volume, with pleural effusion volume assessed by ultrasound and computed tomography (CT) |
| Overall Survival (OS) | through study completion, an average of 1 year | the time from enrollment to death from any cause |
| Incidence of Grade ≥3 treatment-emergent adverse events | through study completion, an average of 1 year | Incidence of Grade ≥3 treatment-emergent adverse events |
| 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 | Dyspnea will be assessed using the modified Medical Research Council (mMRC) Dyspnea Scale. |
| 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 | Quality of life will be assessed using the EORTC QLQ-C30 (core questionnaire) together with the QLQ-LC13 (lung cancer-specific module), or the EuroQol five-dimension questionnaire (EQ-5D). |
Countries
China
Contacts
CONTACTGang Hou, PhD
CONTACTLiwei Liao, PhD
STUDY_DIRECTORGang Hou, PhD
China-Japan Friendship Hospital
Outcome results
None listed