Esophageal Squamous Cell Carcinoma (ESCC)Phase 2NCT07142421
A Study of Trifluridine/Tipiracil Combined With Anlotinib as Second-line Treatment for Recurrent and Metastatic Esophageal Squamous Cell Carcinoma
A Phase 2 study testing Combination therapy (COMB) in people with Esophageal Squamous Cell Carcinoma (ESCC), run by First Affiliated Hospital of Zhejiang University at 1 site in China.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Esophageal Squamous Cell Carcinoma (ESCC)
- What is being tested?
- Combination therapy (COMB)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteChina
- Study dates
- 6 Aug 2025to 30 Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site
The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310003
About this study
Official title: A Phase II Clinical 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.
Read more
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.
- Being tested
- Combination therapy (COMB)
- Keywords
- escc, second-line treatment, Anlotinib, Trifluridine and Tipiracil
- Medical subject headings
- Esophageal Squamous Cell Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combination therapy (COMB)Drug
Also called Trifluridine/tipiracil, Anlotinib
Trifluridine/tipiracil combined with Anlotinib in treatment
| Study group | Role | What they receive |
|---|---|---|
| Trifluridine/tipiracil combined with Anlotinib Group | Experimental | Trifluridine/tipiracil combined with Anlotinib for second-line treatment of recurrent and metastatic ESCC Receives: Drug: Combination therapy (COMB) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival (PFS)
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).
Measured: 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
Secondary outcomes (1)
Overall Survival (OS)
OS focuses on the time from the start of treatment to the patient's death (regardless of the cause)
Measured: From date of therapy until the date of death, assessed up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2025
- Study start6 Aug 2025
- Primary completion31 Aug 2027 (estimated)
- Study completion30 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Esophageal Squamous Cell Carcinoma (ESCC)Studies of the same condition, open and under way.
- More trials run by First Affiliated Hospital of Zhejiang UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital of Zhejiang University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, QiangfengWang, First Affiliated Hospital of Zhejiang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07142421
- Sponsor's protocol ID
- [2025C]IIT. No.123
- Status last verified
- Aug 2025
- First submitted
- 10 Aug 2025
- Last updated
- 26 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Clinical Study of Trifluridine/Tipiracil Combined With Anlotinib as Second-line Treatment for Recurrent and Metastatic Esophageal Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT07142421
- Acronym / sponsor ID
- [2025C]IIT. No.123
- Keywords
- escc, second-line treatment, Anlotinib, Trifluridine and Tipiracil
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- First Affiliated Hospital of Zhejiang UniversityUniversity, hospital or other
- Study start
- 6 Aug 2025 (actual)
- Primary completion
- 31 Aug 2027 (estimated)
- Study completion
- 30 Dec 2027 (estimated)
- First posted
- 26 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Trifluridine/tipiracil combined with Anlotinib Group | Experimental | Drug: Combination therapy (COMB)Trifluridine/tipiracil combined with Anlotinib for second-line treatment of recurrent and metastatic ESCC |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Combination therapy (COMB)Also: Trifluridine/tipiracil, AnlotinibTrifluridine/tipiracil combined with Anlotinib in treatment | Drug | Trifluridine/tipiracil combined with Anlotinib Group |
Primary outcome
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).
1 secondary outcome
Overall Survival (OS)
Time frame: From date of therapy until the date of death, assessed up to 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Combination therapy (COMB) in people with Esophageal Squamous Cell Carcinoma (ESCC), run by First Affiliated Hospital of Zhejiang University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 26 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2025.