First-in-Human Expanded Cohort Study of Intrapleural Administration of TolueneSulfonamide in Patients With Malignant Pleural Effusion

Overview

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

• Drug Intrapleural 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 injec
• Drug Intrapleural 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

Primary outcome measures

• Objective Response Rate [Time frame: 4 weeks, 12 weeks, 6 months, and 12 months after treatment completion]

Secondary outcome measures (5)

• Percentage Change in Pleural Effusion Volume [Time frame: 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) [Time frame: through study completion, an average of 1 year]
• Incidence of Grade ≥3 treatment-emergent adverse events [Time frame: through study completion, an average of 1 year]
• mMRC Dyspnea Score [Time frame: 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 [Time frame: 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]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

China · 1 center

• China-Japan Friendship Hospital — Beijing

Publications

• Guan WJ, Li SY, Zhong NS. Effects of para-toluenesulfonamide intratumoral injection on pulmonary adenoid cystic carcinoma complicating with severe central airway obstruction: a 5-year follow-up study. J Thorac Dis. 2018 Apr;10(4):2448-2455. doi: 10.21037/jtd.2018.03.70. PMID 29850151
• Li SY, Li Q, Guan WJ, Huang J, Yang HP, Wu GM, Jin FG, Hu CP, Chen LA, Xu GL, Liu SZ, Wu CG, Han BH, Xiang Y, Zhao JP, Wang J, Zhou X, Li HP, Zhong NS. Effects of para-toluenesulfonamide intratumoral injection on non-small cell lung carcinoma with severe central airway obstruction: A multi-center, non-randomized, single-arm, open-label trial. Lung Cancer. 2016 Aug;98:43-50. doi: 10.1016/j.lungcan. PMID 27393505
• Xu YF, Chen YR, Bu FL, Huang YB, Sun YX, Li CY, Sellick J, Liu JP, Qin DM, Liu ZL. Chinese herbal injections versus intrapleural cisplatin for lung cancer patients with malignant pleural effusion: A Bayesian network meta-analysis of randomized controlled trials. Front Oncol. 2022 Sep 20;12:942941. doi: 10.3389/fonc.2022.942941. eCollection 2022. PMID 36203451
• Dong X, Huang Y, Yi T, Hu C, Gao Q, Chen Y, Zhang J, Chen J, Liu L, Meng R, Zhang S, Dai X, Fei S, Jin Y, Yin P, Hu Y, Wu G. Intrapleural infusion of tumor cell-derived microparticles packaging methotrexate or saline combined with pemetrexed-cisplatin chemotherapy for the treatment of malignant pleural effusion in advanced non-squamous non-small cell lung cancer: A double-blind, randomized, placeb PMID 36275698
• Feller-Kopman DJ, Reddy CB, DeCamp MM, Diekemper RL, Gould MK, Henry T, Iyer NP, Lee YCG, Lewis SZ, Maskell NA, Rahman NM, Sterman DH, Wahidi MM, Balekian AA. Management of Malignant Pleural Effusions. An Official ATS/STS/STR Clinical Practice Guideline. Am J Respir Crit Care Med. 2018 Oct 1;198(7):839-849. doi: 10.1164/rccm.201807-1415ST. PMID 30272503
• Porcel JM, Cordovilla R, Tazi-Mezalek R, Barrios-Barreto D, Perez-Pallares J, Novais E Bastos H, Martinez-Tomas R, Flandes-Aldeyturriaga J, Cases-Viedma E, Recalde B, Botana-Rial M. Efficacy and Safety of Indwelling Catheter for Malignant Pleural Effusions Related to Timing of Cancer Therapy: A Systematic Review. Arch Bronconeumol. 2023 Sep;59(9):566-574. doi: 10.1016/j.arbres.2023.06.007. Epub 20 PMID 37429748
• 北京肿瘤学会临床研究专委会，中国医院协会肿瘤医院分会，王书航，等。恶性胸腔积液干预性临床研究设计专家共识[J]. 中华肿瘤防治杂志, 2025,32(8): 455-461.
• Kumar A, Xu B, Srinivasan D, Potter AL, Raman V, Lanuti M, Yang CJ, Auchincloss HG. Long-Term Survival of American Joint Committee on Cancer 8th Edition Staging Descriptors for Clinical M1a Non-Small Cell Lung Cancer. Chest. 2024 Mar;165(3):725-737. doi: 10.1016/j.chest.2023.07.4220. Epub 2023 Aug 5. PMID 37544427

Identifiers

NCT: NCT07332858 · 2025-HX-183

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗