Consolidation of Toripalimab and Capecitabine After Chemoradiotherapy in ESCC

NCT07177794 | Recruiting Phase 3 DMC

• 1 other identifier: B2025-404-01
• Study Type: interventional
• Target: 242
• Locations: 1 country
• Sites: 1

Brief Summary

Definitive chemoradiotherapy (CRT) is the standard treatment for locally advanced unresectable esophageal cancer, but its efficacy remains unsatisfactory. More importantly, there is a lack of effective consolidation treatment after CRT, resulting in a high recurrence rate. Our previous prospective phase II trial (EC-CRT-001) demonstrated that the addition of toripalimab to definitive CRT improved the complete response rate in patients with locally advanced esophageal squamous cell carcinoma (ESCC), showing potential for enhanced long-term survival with a manageable safety profile. Nevertheless, the risk of recurrence requires further reduction. Metronomic capecitabine chemotherapy can modulate the tumor immune microenvironment and may synergize with PD-1 antibodies to enhance antitumor efficacy, potentially further prolonging survival in ESCC. Based on current research advances and our preliminary findings, this randomized, controlled, multicenter, phase III clinical trial aims to evaluate the efficacy and safety of toripalimab combined with capecitabine as maintenance therapy for patients with locally advanced ESCC who have not progressed after definitive CRT.

Conditions

Esophageal Cancer; Chemoradiotherapy

Keywords

Esophageal squamous cell carcinoma; definitive chemoradiotherapy; maintenance therapy; Toripalimab

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Three-year follow-up from the date of enrollment to the date of disease progression or last follow-up

  From date of enrollment until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 36 months

Secondary Outcomes (3)

• Overall survival

  From date of enrollment until the date of death from any cause or the date of last follow-up, whichever came first, assessed up to 36 months

• Clinical complete response

  14-16 weeks after the completion of radiotherapy

• Treatment-related adverse events

  From date of enrollment to the date of last follow-up, assessed up to 36 months.

Other Outcomes (2)

• Correlation between immune signature and overall survival

  From date of enrollment to the date of last follow-up, assessed up to 36 months.

• Correlation between dynamic change of ctDNA and overall survival

  From date of enrollment to the date of last follow-up, assessed up to 36 months.

Study Arms (2)

Arm A

EXPERIMENTAL

Patients will receive toripalimab combined with metronomic capecitabine, with a maximum treatment duration of one year (toripalimab 240 mg, IV drip, Q3W, for 16 cycles; capecitabine 500 mg, twice daily, orally).

Drug: toripalimab; Drug: capecitabine

Arm B

NO INTERVENTION

Patients will undergo conventional observation and follow-up.

Interventions

toripalimab DRUG

Patients will receive toripalimab with a maximum treatment duration of one year (240 mg, IV drip, Q3W, for 16 cycles).

Also known as: JS001

Arm A

capecitabine DRUG

Patients will receive metronomic capecitabine, with a maximum treatment duration of one year (500 mg, twice daily, orally).

Also known as: Xeloda

Arm A

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed squamous cell carcinoma of the esophagus;
• Locally advanced esophageal cancer classified as stage I-IVA (inoperable or patient declined surgery) or stage IVB thoracic esophageal cancer with supraclavicular lymph node metastasis only (AJCC 8th edition) prior to treatment;
• Completion of definitive concurrent chemoradiotherapy without disease progression; radiotherapy dose of 50-50.4 Gy using conventional fractionation and IMRT technique; concurrent platinum- or taxane-based doublet chemotherapy during radiotherapy; ≤4 cycles of induction chemotherapy allowed prior to radiotherapy; PD-1/PD-L1 antibody therapy permitted during induction chemotherapy and radiotherapy; no adjuvant therapy received;
• Enrollment window: within 1-42 days after completion of chemoradiotherapy;
• Age 18-75 years;
• Estimated life expectancy \>6 months;
• Eastern Cooperative Oncology Group performance status ≤ 2;
• The function of important organs meets the following requirements: a. white blood cell count (WBC) ≥3.5×109/L, absolute neutrophil count (ANC) ≥1.5×109/L; b. platelets ≥75×109/L; c. hemoglobin ≥9g/dL; d. serum albumin ≥2.8g/dL; e. total bilirubin ≤1.5×ULN, ALT, AST and/or AKP ≤2.5×ULN; f. serum creatinine ≤1.5×ULN or creatinine clearance rate \>60 mL/min;
• Ability to understand the trial details and has provided written informed consent.

You may not qualify if:

• Patients who have received antitumor therapy (including adjuvant chemotherapy, surgery, immunotherapy, targeted therapy, etc.) after completion of chemoradiotherapy;
• Stage IVb patients with metastasis to solid organs (e.g., liver, bone, lung, brain, adrenal gland, peritoneum, etc.) at initial diagnosis;
• Known or suspected allergy to the investigational drug(s) or any agent related to the trial regimen;
• Presence of esophageal fistula and/or esophageal hemorrhage prior to enrollment;
• Disease progression after chemoradiotherapy;
• ≥Grade 2 radiation pneumonitis prior to enrollment;
• History of ≥ Grade 3 immune-related adverse events prior to enrollment;
• Prior treatment with targeted drugs;
• History of other malignant tumors besides esophageal cancer, except for non-melanoma skin cancer, carcinoma in situ of the cervix, papillary thyroid carcinoma, or cured early-stage prostate cancer;
• Patients with severe cardiac, pulmonary, hepatic, or renal dysfunction, hematopoietic system diseases, cachexia, or other conditions that make them unfit for chemotherapy;
• Female patients who are pregnant or breastfeeding;
• Inability to provide informed consent due to psychological, familial, social, or other factors;
• Presence of CTC grade ≥2 peripheral neuropathy;
• Patients with a history of diabetes for more than 10 years and poorly controlled blood glucose levels;
• History of autoimmune disease or autoimmune disorders (e.g., colitis, systemic lupus erythematosus, rheumatoid arthritis, uveitis, hypophysitis, hyperthyroidism; not limited to these diseases or syndromes), immunodeficiency history, including HIV positivity, or other acquired/congenital immunodeficiency disorders, or history of organ transplantation or allogeneic bone marrow transplantation;

Sponsors & Collaborators

• Sun Yat-sen University: lead
• First Affiliated Hospital, Sun Yat-Sen University: collaborator
• Fifth Affiliated Hospital, Sun Yat-Sen University: collaborator
• Zhongshan People's Hospital, Guangdong, China: collaborator

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (3)

• Zhu Y, Wen J, Li Q, Chen B, Zhao L, Liu S, Yang Y, Wang S, Lv Y, Li J, Zhang L, Hu Y, Liu M, Xi M. Toripalimab combined with definitive chemoradiotherapy in locally advanced oesophageal squamous cell carcinoma (EC-CRT-001): a single-arm, phase 2 trial. Lancet Oncol. 2023 Apr;24(4):371-382. doi: 10.1016/S1470-2045(23)00060-8.

  PMID: 36990609 RESULT

• Bando H, Kumagai S, Kotani D, Mishima S, Irie T, Itahashi K, Tanaka Y, Habu T, Fukaya S, Kondo M, Tsushima T, Hara H, Kadowaki S, Kato K, Chin K, Yamaguchi K, Kageyama SI, Hojo H, Nakamura M, Tachibana H, Wakabayashi M, Fukui M, Fuse N, Koyama S, Mano H, Nishikawa H, Shitara K, Yoshino T, Kojima T. Atezolizumab following definitive chemoradiotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma - a multicenter phase 2 trial (EPOC1802). Nat Cancer. 2025 Mar;6(3):445-459. doi: 10.1038/s43018-025-00918-1. Epub 2025 Feb 19.

  PMID: 39972105 RESULT

• Jia R, Shan T, Zheng A, Zhang Y, Lu P, Zhang G, Wang F, Xu Z, Zheng G, Tang D, Zhang W, Li W, Li R, Guo Y, Liu L, Luo X, Zheng Y, Chang Z, Wang Q, Wang X, Yuan X, Kong G, Li S, Yang R, Zhou D, Ren J, Yin W, Li J, Zhang J, Wang Z, Sheng M, Xu B, Li L, Liu X, Lu Z, Wan L, Zhou F, Gao S. Capecitabine or Capecitabine Plus Oxaliplatin Versus Fluorouracil Plus Cisplatin in Definitive Concurrent Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma (CRTCOESC): A Multicenter, Randomized, Open-Label, Phase 3 Trial. J Clin Oncol. 2024 Jul 10;42(20):2436-2445. doi: 10.1200/JCO.23.02009. Epub 2024 May 6.

  PMID: 38710003 RESULT

MeSH Terms

Conditions

Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma

Interventions

toripalimab; Capecitabine

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Mian Xi, MD

  Sun Yat-Sen University Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mian Xi, MD

CONTACT

862087343385; ximian@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 10, 2025
• First Posted: September 17, 2025
• Study Start: September 10, 2025
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): May 31, 2030
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)