Xuan Yin Ning Plus Bevacizumab for Malignant Pleural Effusion

Official title

A Prospective, Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Study of Xuan Yin Ning Formula Combined With Intrapleural Injection of Bevacizumab for the Treatment of Malignant Pleural Effusion.

Overview

The goal of this clinical trial is to determine whether the Xuanyin Ning Formula combined with intrapleural injection of bevacizumab via chest tube drainage is effective in treating malignant pleural effusion. It will also evaluate the safety of this combination therapy. The main questions it aims to answer include: Does the Xuanyin Ning Formula combined with intrapleural injection of bevacizumab via chest tube drainage improve the objective response rate (ORR) of pleural effusion in patients with malignant pleural effusion? Does this combination therapy affect the duration of response (DoR), progression-free survival (PFS), overall survival (OS), degree of dyspnea, quality of life, and Traditional Chinese Medicine (TCM) pattern/syndrome evaluation in patients with malignant pleural effusion? Participants will: Receive intrapleural injection of bevacizumab via chest tube drainage, and take either Xuanyin Ning Formula or placebo granules daily for 8 weeks. Undergo ultrasound assessment of pleural effusion at 2, 4, 8, and 12 weeks after the first intrapleural injection during closed chest drainage, followed by ultrasound assessments every 3 months (±7 days) until pleural effusion progression.

Interventions

• Other Treatment with Xuanyin Ning Formula combined with intrapleural injection of bevacizumab via chest tube drainage
  After chest tube drainage, bevacizumab 300 mg per dose, dissolved in 50 ml of normal saline, is injected intrapleurally. The injection may be repeated after 2 weeks depending on the control of pleural effusion. Xuanyin Ning is taken as 2 sachets per day, one sachet dissolved in water and taken orally in the morning and one in the evening. Each treatment cycle is 4 weeks, and at least 2 cycles are required.
• Drug Placebo granules plus chest tube drainage and intrapleural bevacizumab injection
  After chest tube drainage, bevacizumab 300 mg per dose, dissolved in 50 ml of normal saline, is injected intrapleurally. The injection may be repeated after 2 weeks depending on the control of pleural effusion. Placebo granules are taken as 2 sachets per day, one sachet dissolved in water and taken orally in the morning and one in the evening. Each treatment cycle is 4 weeks, and at least 2 cycles are required.

Primary outcome measures

• Objective Response Rate of pleural effusion (ORR) [Time frame: Before treatment and at 4 weeks, 8 weeks, and 12 weeks after treatment]

Secondary outcome measures (6)

• Duration of Response (DoR) [Time frame: At 2, 4, 8, and 12 weeks after treatment]
• Progression-Free Survival (PFS) [Time frame: From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months]
• Overall Survival (OS) [Time frame: From date of treatment until the date of death from any cause, assessed up to 100 months]
• Degree of dyspnea [Time frame: At 2, 4, 8, and 12 weeks after treatment]
• ECOG score [Time frame: At 2, 4, 8, and 12 weeks after treatment]
• Traditional Chinese Medicine (TCM) syndrome evaluation [Time frame: At 2, 4, 8, and 12 weeks after treatment]

Eligibility criteria

Inclusion criteria

• Patients with advanced non-squamous non-small cell lung cancer who have failed at least first-line systemic therapy;
• Presence of unilateral pleural effusion confirmed as malignant by pathology or cytology, with at least moderate volume requiring drainage (moderate pleural effusion defined as: supine ultrasound examination showing pleural effusion ≥3 cm, or sitting ultrasound examination showing pleural effusion ≥4 cm,accompanied by clinical symptoms such as chest tightness and dyspnea);
• Age 18-75 years;
• ECOG performance status 0-2;
• Traditional Chinese Medicine (TCM) syndrome differentiation classified as Xuanyin (suspension fluid) with fluid retention in the chest and hypochondrium;
• Expected survival of at least 3 months;
• Voluntarily signed informed consent before treatment;
• No contraindications to chest tube placement for drainage;
• Adequate major organ function, including:

• Complete blood count:

White blood cell count ≥ 4.0×10⁹/L Absolute neutrophil count ≥ 1.5×10⁹/L Platelet count ≥ 100×10⁹/L Hemoglobin ≥ 90 g/L

• Blood biochemistry:

Total bilirubin ≤ 1.5×ULN ALT ≤ 2.5×ULN, AST ≤ 2.5×ULN Serum creatinine ≤ 1.5×ULN, or creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula)

• Coagulation function:

International normalized ratio (INR) ≤ 1.5×ULN Activated partial thromboplastin time (APTT) ≤ 1.5×ULN

• Blood glucose: within normal range, or diabetic patients under treatment with stable blood glucose control;
• Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours before starting study drug administration, and must use effective contraception (e.g., intrauterine device, contraceptive pills, or condoms) during the study period and for at least 3 months after the last dose. -Male subjects with a partner of childbearing potential must use effective contraception during the study period and for 3 months after the last dose;
• Good subject compliance, able to follow up for efficacy and adverse events/reactions as required by the protocol.

Exclusion criteria

• The location of pleural effusion is unsuitable for drainage, or the patient would not benefit from intrapleural drug administration (e.g., severe loculation/septation);
• Other contraindications to indwelling chest tube placement;
• Pleural effusion with active infection;
• Prior history of ipsilateral chest tube drainage and intrapleural anti-tumor drug therapy or pleurodesis;
• Prior history of empyema or chylothorax;
• Participation in another clinical trial within 4 weeks before signing informed consent;
• Known allergy to any component of the study drugs;
• Severe bleeding tendency or active bleeding;
• Uncontrolled severe hypertension;
• Recent (within 3 months) thromboembolic events, such as deep vein thrombosis, pulmonary embolism, cerebral infarction, etc.;
• Prior severe adverse reactions to intravenous bevacizumab, such as severe proteinuria, gastrointestinal perforation, hypertensive crisis, etc.;
• Severe cardiac, hepatic, or renal insufficiency;
• Pregnant or breastfeeding women;
• Subjects with other active infectious diseases in the acute phase;
• Any other factors that, in the investigator's judgment, may lead to premature termination of the study, such as other serious diseases (including psychiatric disorders) requiring concomitant treatment, alcoholism, drug abuse, family or social factors that may affect the subject's safety or compliance.

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 · 7 centers

• Wuhan First Hospital — Wuhan
• The First Affiliated Hospital of Xinxiang Medical University — Xinxiang
• Weifang Traditional Chinese Medicine Hospital 或 Weifang Traditional Chinese Hospital — Weifang
• Shanghai Chest Hospital — Shanghai
• Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine — Shanghai
• Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai Universi — Shanghai
• Shanghai Tenth People's Hospital Chongming Branch — Shanghai

Identifiers

NCT: NCT07670338 · ZDYN-2024-A-147

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗