A Prospective Randomized Controlled Clinical Trial of Intensive Nutritional Support in Conversion Therapy for Locally Advanced Unresectable Esophageal Squamous Cell Carcinoma
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Sichuan University
- Enrollment
- 118
- Locations
- 1
- Primary Endpoint
- Pathological Complete Response (pCR) Rate
Overview
Brief Summary
Malnutrition is highly prevalent in patients with upper gastrointestinal tumors, which may negatively impact treatment tolerance and anti-tumor immune responses. This study aims to evaluate the efficacy and safety of intensive enteral nutritional support in patients with locally advanced unresectable esophageal squamous cell carcinoma (ESCC) undergoing conversion therapy. Participants receiving PD-1 inhibitors combined with chemotherapy will be randomly assigned to either intensive nutritional support or standard care. The primary goal is to determine if intensive nutritional support can improve the pathological complete response (pCR) rate after subsequent surgery.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Pathologically confirmed Esophageal Squamous Cell Carcinoma (ESCC). Aged 18-80 years, regardless of gender. ECOG Performance Status (PS) 0-2, and weight loss \< 10% within the past 6 months.
- •Confirmed locally advanced unresectable ESCC according to NCCN Guidelines (Version 2026.1).
- •Planned to receive surgery after completion of conversion therapy, with no surgical contraindications.
- •Treatment-naive: No prior anti-tumor therapy for ESCC, including radiotherapy, chemotherapy, or surgery.
- •Presence of measurable lesion(s) according to RECIST 1.
- •Expected survival ≥ 3 months. Able to swallow and tolerate oral medications. Adequate organ function (blood counts, biochemistry, and coagulation parameters meeting protocol requirements).
- •Women of childbearing age and men must agree to use effective contraception during the study and for 6 months after completion.
- •Voluntary participation with signed informed consent and good compliance.
Exclusion Criteria
- •Presence of esophageal-mediastinal fistula and/or tracheoesophageal fistula, or tumor invasion of major vessels with risk of fatal hemorrhage.
- •History of other malignant tumors within the past 5 years. Current or prior use of immunosuppressants or systemic steroids (\>10 mg/day prednisone equivalent) within 2 weeks prior to first dose.
- •Active autoimmune disease or history of autoimmune disease requiring systemic treatment.
- •Known immunodeficiency history, including HIV infection, organ transplant, or bone marrow transplant.
- •Uncontrolled concurrent diseases (e.g., uncontrolled hypertension, unstable angina, recent myocardial infarction, or severe infections).
- •Active tuberculosis (TB) or history of TB without standardized treatment. Active Hepatitis B (HBV) or Hepatitis C (HCV) infection. Complete inability to take oral enteral nutrition due to esophageal stenosis. History or current presence of interstitial pneumonia or interstitial lung disease.
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
- •Significant gastrointestinal disorders with severe diarrhea (CTCAE \> Grade 2). Pregnant or lactating women. Participation in other clinical trials within 30 days prior to enrollment.
Arms & Interventions
Intensive Nutritional Support Group
Patients in this group receive intensive oral enteral nutritional support in addition to the standard conversion therapy (PD-1 inhibitor plus chemotherapy).
Intervention: PD-1 Inhibitor plus Chemotherapy (Drug)
Intensive Nutritional Support Group
Patients in this group receive intensive oral enteral nutritional support in addition to the standard conversion therapy (PD-1 inhibitor plus chemotherapy).
Intervention: Oral Enteral Nutritional Preparation (Dietary Supplement)
Intensive Nutritional Support Group
Patients in this group receive intensive oral enteral nutritional support in addition to the standard conversion therapy (PD-1 inhibitor plus chemotherapy).
Intervention: Esophagectomy with lymph node dissection (Procedure)
Standard Nutritional Support Group
Patients in this group receive routine nutritional guidance/support in addition to the standard conversion therapy (PD-1 inhibitor plus chemotherapy)
Intervention: PD-1 Inhibitor plus Chemotherapy (Drug)
Standard Nutritional Support Group
Patients in this group receive routine nutritional guidance/support in addition to the standard conversion therapy (PD-1 inhibitor plus chemotherapy)
Intervention: Esophagectomy with lymph node dissection (Procedure)
Outcomes
Primary Outcomes
Pathological Complete Response (pCR) Rate
Time Frame: At the time of surgery (approximately 4-6 weeks after the completion of conversion therapy).
Defined as the absence of residual viable tumor cells in the primary tumor bed and all sampled lymph nodes (ypT0N0) according to the Mandard regression criteria, as evaluated by a blinded Independent Review Committee (BIRC).
Secondary Outcomes
- Event-Free Survival (EFS)(From randomization up to 2 years.)
- Major Pathological Response (MPR) Rate(At the time of surgery (approximately 4-6 weeks after conversion therapy).)
- Objective Response Rate (ORR)(Approximately 2 months (after completion of 2 cycles of conversion therapy).)
Investigators
Zhen-Yu Ding
Professor
West China Hospital