Standardized Management of Esophageal Fistula in Esophageal Squamous Cell Carcinoma

Official title

An Evaluation of the Safety and Efficacy of a Standardized Diagnosis and Treatment Protocol for Esophageal Fistula in Patients With Esophageal Squamous Cell Carcinoma: A Single-Arm, Multi-Center Clinical Study

Overview

This prospective, multi-center, observational registry study (PKU-ESCC-EF) aims to evaluate the safety and effectiveness of a standardized diagnosis and treatment protocol for esophageal fistula (EF) in patients with advanced esophageal squamous cell carcinoma (ESCC). Esophageal fistula is a severe complication that often leads to life-threatening infections and poor nutrition. This study will observe patients receiving a comprehensive management strategy, which includes fistula sealing with esophageal or airway stents, targeted anti-infective therapy, nutritional support, and subsequent systemic anti-tumor therapy. The primary goal is to assess whether this standardized approach can improve overall survival and enable more patients to receive further anti-cancer treatments.

Detailed description

This observational registry employs a prospective, single-arm design to recruit eligible patients with newly diagnosed esophageal fistula (tracheoesophageal or mediastinal fistula) complicating unresectable advanced esophageal squamous cell carcinoma. All enrolled participants will receive management according to a predefined standardized diagnostic and therapeutic protocol. The protocol integrates a comprehensive workflow from diagnostic assessment to multidisciplinary intervention: initial diagnosis is supported by clinical manifestations, imaging studies, and endoscopic evaluation, followed by interventional fistula closure using esophageal or airway covered stents selected according to fistula characteristics. Accompanying medical support includes anti-infective therapy, negative pressure suction, anti-reflux treatment, and nutritional support. After achieving adequate fistula control and clinical stabilization, subsequent systemic anti-tumor therapy may be administered based on investigator assessment. Prospective data collection will encompass fistula sealing status, nutritional parameters, quality of life, subsequent anti-tumor treatment rate, overall survival, and exploratory biomarker analysis of biospecimens, thereby providing real-world evidence to standardize management strategies for this serious complication.

Interventions

• Other Standardized Management Protocol for Esophageal Fistula
  This is a comprehensive, standardized clinical management protocol for esophageal fistula in advanced esophageal squamous cell carcinoma patients. The protocol integrates multiple standardized components into a unified pathway: (1) systematic diagnosis using iodine-contrast esophagography, chest CT, and endoscopy; (2) interventional fistula sealing with covered esophageal/airway stents selected by fistula characteristics; (3) coordinated adjunctive therapy including anti-infectives, acid suppres

Primary outcome measures

• Overall Survival (OS) [Time frame: From date of fistula diagnosis until death from any cause, assessed up to 6 months.]

Secondary outcome measures (6)

• Rate of Subsequent Anti-tumor Therapy [Time frame: From date of fistula diagnosis until the initiation of subsequent anti-tumor therapy, assessed through study completion (up to 6 months).]
• Fistula Sealing Success Rate [Time frame: At 2 weeks and 4 weeks after the initial fistula intervention.]
• Nutritional Status (NRS 2002) [Time frame: From baseline through study completion (up to 6 months).]
• Nutritional Status (PG-SGA) [Time frame: From baseline through study completion (up to 6 months).]
• Quality of Life (QOL) [Time frame: From baseline through study completion (up to 6 months).]
• Incidence of Adverse Events (AEs) [Time frame: From the start of the standardized management protocol until 30 days after the last intervention or through study completion, whichever comes first.]

Eligibility criteria

Inclusion criteria

• Voluntary participation and provision of written informed consent.
• Age between 18 and 75 years (inclusive).
• Histologically confirmed diagnosis of esophageal squamous cell carcinoma.
• Radiologically confirmed unresectable, advanced disease.
• Newly diagnosed esophageal fistula (including tracheoesophageal fistula or mediastinal esophageal fistula).
• Previous receipt of ≤ 3 lines of systemic anti-tumor therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Adequate organ and marrow function within 7 days prior to potential anti-tumor treatment, as defined by:
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L
• Platelet count ≥ 100 × 10⁹/L
• Total bilirubin (TBIL) ≤ 1.5 × the upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (or ≤ 5 × ULN in the presence of liver metastases)
• Serum creatinine ≤ 1.5 × ULN
• Adequate cardiac, pulmonary, and renal function to be eligible for general anesthesia, with no contraindications to general anesthesia.

Exclusion criteria

• Patients with postoperative anastomotic fistula.
• Uncontrolled active bleeding.
• Presence of a concurrent primary malignancy other than esophageal carcinoma.
• Clinically significant cardiovascular disease, including but not limited to:
• Heart failure (NYHA Class III-IV)
• Uncontrolled coronary artery disease, cardiomyopathy, or arrhythmia
• Uncontrolled hypertension
• History of myocardial infarction within the past 1 year
• Neurological or psychiatric disorders that impair cognitive ability, including the presence of central nervous system metastases.
• Uncontrolled, active severe clinical infection ( > Grade 2 per NCI-CTCAE version 5.0) within 14 days prior to enrollment, including active tuberculosis (this is a contraindication for anti-tumor therapy, not for interventional procedures).
• Known or self-reported HIV infection, or active Hepatitis B or Hepatitis C.
• A history of interstitial lung disease (e.g., interstitial pneumonia, pulmonary fibrosis), or evidence of interstitial lung disease on baseline chest X-ray/CT.

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

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07353541 · PKU-ESCC-EF-ORS-001 · 2024YJZ21

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗