Omega-3 Fatty Acids With PD-1 Inhibitors in Advanced Esophageal Cancer (ESO-Shanghai28)

Effect of Omega-3 Fatty Acids on PD-1 Inhibitor Therapy in Advanced Esophageal Cancer (ESO-Shanghai28): A Phase II Randomized Controlled Trial

This is a randomized, double-blind, placebo-controlled phase II clinical trial designed to evaluate whether adding omega-3 fatty acids improves outcomes in adult patients with recurrent or metastatic esophageal cancer receiving PD-1 inhibitor therapy.

The main questions are:

Compared with placebo, does omega-3 (EPA+DHA) increase the longitudinal change in skeletal muscle index (ΔSMI) over 6 months? Does it improve clinical outcomes and favorably modulate immune and metabolic biomarkers as well as patient-reported outcomes ?

Participants will be randomized 1:1 to:

Intervention: Standard PD-1 therapy plus oral omega-3 (EPA 2.5 g + DHA 1.25 g per day) for 6 months.

Control: Standard PD-1 therapy plus matching placebo for 6 months. Participants will attend study visits at baseline, 3 months, and 6 months (then every 3 months up to 2 years), undergo body composition and functional assessments, blood sampling, and questionnaires, and have treatment adherence assessed per protocol. Pre-specified exploratory biomarker analyses will be conducted to support mechanism research.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Neoplasms
• Intervention / Treatment: Dietary supplement: PD-1 + Omega-3 Fatty Acids (EPA/DHA); Dietary supplement: PD-1 + Placebo (Oral Drops)

• Study Type: Interventional
• Enrollment (Estimated): 142
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: kuai le zhao Prof; Phone Number: 021-64175590; Email: 30635279@qq.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria： Age ≥18 years; ECOG 0-2. Histologically confirmed recurrent/metastatic esophageal cancer (AJCC 8th; de novo stage IV or relapse after prior therapy).

PD-1 inhibitor naïve, or prior PD-1 stopped >3 months with subsequent progression (not primary PD-1 resistance).

Adequate organ function per protocol (hematologic, hepatic, renal). Women of childbearing potential: negative pregnancy test and agree to effective contraception.

Signed informed consent.

Exclusion Criteria： PD-1 inhibitor resistance or refractory disease to prior PD-1. Esophageal fistula present or strongly suspected. Active autoimmune disease or immunodeficiency requiring systemic therapy (protocol-defined exceptions allowed, e.g., treated hypothyroidism; controlled type 1 diabetes).

Systemic corticosteroids or other immunosuppressants requiring ongoing use (physiologic or topical steroids allowed).

Interstitial lung disease/pneumonitis history or active pneumonitis on screening CT.

Uncontrolled cardiovascular disease (e.g., NYHA ≥ II heart failure, unstable angina, recent MI, significant uncontrolled arrhythmias).

Serious active infection, including active TB; uncontrolled viral hepatitis (active HBV/HCV per protocol).

Pregnant or breastfeeding. Recent major surgery (per protocol window) or high bleeding risk/therapeutic anticoagulation not suitable for omega-3 use.

Other conditions that, in investigator's judgment, preclude protocol compliance or safety.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PD-1 + Omega-3 (EPA/DHA)	Dietary supplement: PD-1 + Omega-3 Fatty Acids (EPA/DHA); Intervention: Omega-3 (EPA 2.5 g + DHA 1.25 g/day) oral drops × 6 months; with PD-1; blinded; adherence via check-ins/bottle counts/plasma EPA/DHA.
Placebo Comparator: PD-1 + Placebo	Dietary supplement: PD-1 + Placebo (Oral Drops); Comparator: Matching placebo oral drops × 6 months; with PD-1; blinded; adherence via check-ins/bottle counts.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Skeletal Muscle Index (ΔSMI) From Baseline to 6 Months	From randomization to Month 6 (±4 weeks)

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2025
• Primary Completion (Estimated): June 5, 2027
• Study Completion (Estimated): June 5, 2027

Study Registration Dates

• First Submitted: November 27, 2025
• First Submitted That Met QC Criteria: December 8, 2025
• First Posted (Estimated): December 9, 2025

Study Record Updates

• Last Update Posted (Estimated): December 9, 2025
• Last Update Submitted That Met QC Criteria: December 8, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Fatty Acids; Lipids; Fatty Acids, Unsaturated; Oils; Dietary Fats; Fats; Dietary Fats, Unsaturated; Fish Oils; Fatty Acids, Omega-3
• Other Study ID Numbers: ESO-Shanghai28

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) underlying the primary publication will be shared with qualified researchers for legitimate scientific purposes. Data will be de-identified per HIPAA and local regulations.
• IPD Sharing Time Frame: Beginning 12 months after primary results publication and for 5 years thereafter.
• IPD Sharing Access Criteria: Researchers must submit a methodologically sound proposal, IRB/ethics approval (or exemption), and a signed data use agreement. Proposals will be reviewed by the sponsor/investigator committee.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No