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NCT Number: NCT07142421

A Study of Trifluridine/Tipiracil Combined With Anlotinib as Second-line Treatment for Recurrent and Metastatic Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the malignant tumors with a high incidence worldwide, especially remaining persistently high in Asian regions. Despite advancements in early diagnosis and comprehensive treatment, most patients are already in the locally advanced or metastatic stage at the time of initial diagnosis, resulting in an extremely poor prognosis. The objective response rate (ORR) of first-line chemotherapy regimens (such as platinum-containing dual-drug combinations with fluorouracil) is less than 50%, and the median progression-free survival (PFS) is only 3-6 months. Moreover, the options for second-line treatment are more limited. Currently, there is no unified standard for second-line treatment, and there is an urgent need to explore new and effective regimens.

Anlotinib is a multi-target tyrosine kinase inhibitor that can target and inhibit vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), and platelet-derived growth factor receptor (PDGFR). It exerts anti-tumor effects through anti-angiogenesis and regulation of the tumor microenvironment. Single-agent anlotinib has shown certain efficacy in advanced esophageal cancer. A phase II study indicated that the ORR of single-agent anlotinib in second-line treatment was 9.7%, with a median PFS of 3.0 months.

Suyuan (trifluridine/tipiracil) is a new oral fluoropyrimidine drug composed of trifluridine (a cytotoxic component) and tipiracil (a synergist that inhibits the metabolic enzyme TP), which can overcome the resistance to traditional fluorouracil. Single-agent Suyuan has achieved significant survival benefits in metastatic colorectal cancer, and its synergistic effect in combination with anti-angiogenic drugs in solid tumors has also been preliminarily confirmed.

The biological basis of combination therapy: Anti-angiogenic drugs can improve the hypoxic state of the tumor microenvironment, enhance the delivery efficiency of chemotherapy drugs, and simultaneously inhibit the infiltration of immunosuppressive cells. Their combination with chemotherapy or immunotherapy has potential synergistic effects. Preclinical studies have shown that anlotinib combined with fluoropyrimidine drugs can significantly inhibit the growth of esophageal cancer models by dual inhibition of tumor proliferation and angiogenesis pathways.

Based on the above background, this study intends to explore the efficacy and safety of Suyuan combined with anlotinib in the second-line treatment of recurrent and metastatic ESCC, aiming to provide new treatment options for patients.

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Key information

Conditions

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

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients with pathologically confirmed esophageal squamous cell carcinoma.
  • Clinical stage IIIB-C or IV according to the 8th edition of AJCC.
  • Having at least one measurable or evaluable lesion.
  • ECOG performance status score of 0-2.
  • Failed first-line standard treatment regimens.
  • Age ≥ 18 years.
  • Normal function of major organs.
  • Female subjects of childbearing age must undergo a pregnancy test within 3 days before the first dose with a negative result, and adopt effective contraceptive measures during the study period.

Exclusion criteria

  • Patients with other malignant tumors requiring treatment.
  • Patients with severe diseases of major organs such as heart, liver, and kidney.
  • Patients who have previously received treatment with anti-angiogenic monoclonal antibodies or small-molecule tyrosine kinase inhibitors.
  • Patients with an expected survival period of < 3 months.
  • Patients who have previously used fluoropyrimidine drugs (such as 5-FU, capecitabine, etc.).
  • Patients with Uncontrolled active infections (such as HIV, HCV, HBV, etc.).
  • Pregnant or lactating women.
  • Other circumstances deemed unsuitable for enrollment by the researcher.

Treatment and study plan

Combination therapy (COMB)

Drug

Trifluridine/tipiracil combined with Anlotinib in treatment

Other names: Trifluridine/tipiracil, Anlotinib

Primary outcomes

  1. Progression-Free Survival (PFS)

    Time frame: From date of therapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

    The time interval from the day a patient starts receiving a certain treatment (or is randomized into a treatment regimen) to the occurrence of objective tumor progression (or death from any cause).

Secondary outcomes

  1. Overall Survival (OS)

    Time frame: From date of therapy until the date of death, assessed up to 24 months

    OS focuses on the time from the start of treatment to the patient's death (regardless of the cause)

Sponsors and collaborators

Lead sponsor

First Affiliated Hospital of Zhejiang University

Other

Registry information

Official study title

A Phase II Clinical Study of Trifluridine/Tipiracil Combined With Anlotinib as Second-line Treatment for Recurrent and Metastatic Esophageal Squamous Cell Carcinoma

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Aug 26, 2025
Registry last updated
Aug 26, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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