Esophageal CancerPhase 3SIGNNCT07788001
A Non-inferiority Study of Indocyanine Green-guided Sentinel Lymph Node Mapping Versus Conventional Lymph Node Dissection in Esophageal Cancer
A Phase 3 study testing ICG-guided sentinel lymph node dissection and ICG-guided systematic lymph node dissection in people with Esophageal Cancer and Sentinel Lymph Node, run by Fujian Medical University Union Hospital at 1 site in China.
Trial summary
In the comprehensive treatment system for esophageal cancer, surgical resection combined with regional lymph node dissection remains the core component for achieving cure in patients with resectable esophageal squamous cell carcinoma (ESCC). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Esophageal Cancer, Sentinel Lymph Node, Lymphadenectomy
- What is being tested?
- ICG-guided sentinel lymph node dissection and ICG-guided systematic lymph node dissection
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteChina
- Study dates
- 1 Oct 2026to 1 Oct 2031
- Phase
- Phase 3
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18 to 75 years, regardless of gender;
- Histopathologically confirmed esophageal squamous cell carcinoma or adenocarcinoma by endoscopic biopsy (including esophagogastric junction carcinoma, Siewert type I/II);
- Preoperative clinical stage cT1-3N0M0 (based on contrast-enhanced CT ± PET-CT ± endoscopic ultrasound evaluation);
- No prior neoadjuvant therapy of any form (including chemotherapy, radiotherapy, chemoradiotherapy, immunotherapy, targeted therapy, etc.);
- Scheduled for minimally invasive radical esophagectomy (combined thoracoscopic and laparoscopic McKeown or Ivor-Lewis procedure);
- No surgical contraindications, with cardiac, pulmonary, hepatic, and renal functions sufficient to tolerate surgery;
- ECOG performance status score of 0 to 1;
- Written informed consent signed by the patient or legal representative.
Who cannot join
- Preoperative imaging clearly indicating lymph node metastasis (cN+) or distant metastasis (cM1);
- Prior systemic or local treatment for esophageal cancer of any kind (including chemotherapy, radiotherapy, chemoradiotherapy, immunotherapy, etc.);
- Previous history of esophageal or gastric surgery (except endoscopic mucosal resection/submucosal dissection);
- History of allergy to iodine contrast agents or indocyanine green;
- Severe hepatic or renal insufficiency (Child-Pugh class B or C; serum creatinine ≥ 1.5 times the upper limit of normal);
- Uncontrolled hyperthyroidism;
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- Concomitant other malignancies requiring simultaneous treatment;
- Pregnant or lactating women;
- Other conditions deemed unsuitable for enrollment by the investigator.
- Withdrawal Criteria
- Intraoperative exploration revealing inability to achieve radical resection (R2 resection) or extensive thoracic and abdominal metastasis;
- Intraoperative exploration revealing definite lymph node metastasis (cN+) inconsistent with preoperative staging;
- Severe allergic reaction after ICG injection requiring discontinuation of the study;
- Intraoperative change of surgical plan due to severe complications;
- Withdrawal of informed consent by the patient.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Fujian Medical University Union Hospital
Fuzhou, Fujian, 350000
Bin Zheng, 15959002753, lacustrian@163.com
About this study
Official title: Indocyanine Green-guided Sentinel Lymph Node Dissection Versus Systematic Lymph Node Dissection in cN0 Esophageal Squamous Cell Carcinoma: a Multicenter, Prospective, Non-inferiority Randomized Controlled Trial
In the comprehensive treatment system for esophageal cancer, surgical resection combined with regional lymph node dissection remains the core component for achieving cure in patients with resectable esophageal squamous cell carcinoma (ESCC). The traditional surgical concept holds that the more thorough the lymph node dissection, the better. However, increasing basic and clinical evidence indicates that lymph nodes without metastasis-particularly tumor-draining lymph nodes-play an irreplaceable role in maintaining the host's anti-tumor immune response. Preclinical studies have found that radiation exposure to tumor-draining lymph nodes can impair the efficacy of radiotherapy combined with immunotherapy. In the surgical field, this shift in understanding has given rise to an important clinical question: in radical esophagectomy for esophageal cancer, is it possible to maximally preserve non-metastatic normal lymph nodes while ensuring complete removal of metastatic lymph nodes? If achievable, patients may not only benefit from reduced postoperative complications (such as chylothorax and recurrent laryngeal nerve injury) but also retain important immune organ function, providing a stronger basis for subsequent immunotherapy responses. Therefore, this study intends to conduct a multicenter, prospective, randomized controlled, non-inferiority trial in patients with cT1-3N0M0 esophageal squamous cell carcinoma who have not received neoadjuvant therapy, to evaluate the oncological safety of sentinel lymph node dissection based on the ICG near-infrared fluorescence imaging system in radical esophagectomy for esophageal cancer.
During the study, ICG will be injected around the tumor under intraoperative gastroscopy guidance, followed by tracking of fluorescent lymph nodes using a thoracoscopic near-infrared camera. Professional thoracic surgeons will group and mark these lymph nodes for intraoperative frozen pathology. If intraoperative frozen section shows negative sentinel lymph nodes, patients will be randomized 1:1 into two groups: one group will undergo esophagectomy alone without further lymph node dissection, while the other group will undergo conventional lymph node dissection plus esophagectomy. The primary objective of this study is to evaluate the non-inferiority of ICG-guided sentinel lymph node dissection compared with conventional systematic lymph node dissection in terms of 3-year disease-free survival in patients with cT1-3N0M0 esophageal squamous cell carcinoma who have not received neoadjuvant therapy, thereby validating the oncological safety of the sentinel lymph node dissection strategy.
Read more
Participants will:
- Undergo minimally invasive ESCC surgery within 2 weeks of enrollment, including the 14th day.
- Receive ICG injection around the tumor under intraoperative gastroscopy guidance during surgery.
- Have perioperative, postoperative pathology, and complication information recorded.
- Undergo standardized follow-up after surgery.
Read the detailed description
This study will enroll patients with cT1-3N0M0 esophageal cancer who have not received neoadjuvant therapy. If intraoperative frozen section shows negative sentinel lymph nodes, patients will be randomly assigned into two groups: the experimental group will undergo sentinel lymph node dissection only plus esophagectomy, while the control group will undergo conventional lymph node dissection plus esophagectomy. The investigators will compare the 3-year disease-free survival rate, postoperative complication rate, and other outcomes between the two groups to evaluate the oncological safety of sentinel lymph node dissection based on the ICG near-infrared fluorescence imaging system in radical esophagectomy for esophageal cancer.
- Conditions
- Esophageal Cancer, Sentinel Lymph Node, Lymphadenectomy, Indocyanine Green (ICG), Disease Free Survival
- Being tested
- ICG-guided sentinel lymph node dissection, ICG-guided systematic lymph node dissection
- Medical subject headings
- Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ICG-guided sentinel lymph node dissectionDrug
In the experimental group, the investigators will perform only sentinel lymph node dissection and esophagectomy, without further lymph node resection. This intervention is distinguished by its de-escalated surgical approach: unlike conventional radical esophagectomy with systematic lymph node dissection, no additional lymph node stations will be removed beyond the identified sentinel lymph nodes. By preserving non-sentinel regional lymph nodes, this strategy aims to reduce surgical trauma and postoperative complications-such as chylothorax and recurrent laryngeal nerve injury-while maintaining oncological safety in patients with cT1-3N0M0 esophageal squamous cell carcinoma.
ICG-guided systematic lymph node dissectionDrug
In the control group, in addition to dissecting the sentinel lymph nodes, the investigators will proceed with standard two-field or three-field lymph node dissection for esophageal cancer.
| Study group | Role | What they receive |
|---|---|---|
| ICG-guided sentinel lymph node dissection only plus esophagectomy | Experimental | The experimental group will undergo sentinel lymph node dissection only plus esophagectomy Receives: Drug: ICG-guided sentinel lymph node dissection |
| ICG-guided systematic lymph node dissection plus esophagectomy | Active comparator | The control group will undergo conventional lymph node dissection plus esophagectomy Receives: Drug: ICG-guided systematic lymph node dissection |
What is being measured
The primary outcome is the main question the study is designed to answer.
3-year Disease free survival rate
3-year disease-free survival rate: defined as the time from randomization to the first occurrence of any of the following events: local recurrence, regional lymph node recurrence, distant metastasis, or death from any cause
Measured: The time from randomization to the first occurrence of any of the following events (local recurrence, regional lymph node recurrence, distant metastasis, or death from any cause), assessed up to 36 months.
Secondary outcomes (5)
Postoperative complications
The incidence of severe complications with Clavien-Dindo grade ≥ III within 30 days after surgery; the incidence of specific complications such as chylothorax, recurrent laryngeal nerve injury, anastomotic leakage, and pulmonary infection.
Measured: 30 days after surgery
Immune status indicators
Immune status indicators: changes in peripheral blood lymphocyte subsets (CD4+, CD8+, NK cells) counts before and after surgery.
Measured: Baseline (day -1), post-operative day 1, day 7, and month 1.
lmmune status indicators
lmmune status indicators: changes in peripheral blood lymphocyte subsets (CD4+CD8+, NK cells) rates before and after surgery.
Measured: Baseline (day -1), post-operative day 1, day 7, and month 1.
3-year Overall Survival rate
3-year Overall Survival rate
Measured: 3-year after surgery
Diagnostic performance of ICG
Diagnostic performance of ICG (using postoperative routine pathology as the gold standard): sensitivity, specificity, positive predictive value, negative predictive value, and false negative rate of ICG in identifying sentinel lymph nodes.
Measured: 7-day after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2026
- Study start1 Oct 2026 (estimated)
- Primary completion1 Oct 2028 (estimated)
- Study completion1 Oct 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Esophageal CancerStudies of the same condition, open and under way.
- More trials run by Fujian Medical University Union HospitalThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fujian Medical University Union Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Henan Cancer Hospital, The First Affiliated Hospital of Xiamen University, The University of Hong Kong, Shengjing Hospital, Sichuan Cancer Hospital and Research Institute, Zhangzhou Municipal Hospital of Fujian Province
- Responsible party
- Sponsor
- Investigators
- Bin Zheng, Principal investigator, Fujian Medical University Union Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07788001
- Sponsor's protocol ID
- SIGN study
- Acronym
- SIGN
- Status last verified
- Jun 2026
- First submitted
- 18 Aug 2026
- Last updated
- 26 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- 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 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Indocyanine Green-guided Sentinel Lymph Node Dissection Versus Systematic Lymph Node Dissection in cN0 Esophageal Squamous Cell Carcinoma: a Multicenter, Prospective, Non-inferiority Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07788001
- Acronym / sponsor ID
- SIGN / SIGN study
- Conditions
- Esophageal Cancer, Sentinel Lymph Node, Lymphadenectomy, Indocyanine Green (ICG), Disease Free Survival
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Fujian Medical University Union HospitalUniversity, hospital or other
- Collaborators
- Henan Cancer Hospital, The First Affiliated Hospital of Xiamen University, The University of Hong Kong, Shengjing Hospital, Sichuan Cancer Hospital and Research Institute, Zhangzhou Municipal Hospital of Fujian Province
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 1 Oct 2028 (estimated)
- Study completion
- 1 Oct 2031 (estimated)
- First posted
- 26 Aug 2026 (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.
In the comprehensive treatment system for esophageal cancer, surgical resection combined with regional lymph node dissection remains the core component for achieving cure in patients with resectable esophageal squamous cell carcinoma (ESCC). The traditional surgical concept holds that the more thorough the lymph node dissection, the better. However, increasing basic and clinical evidence indicates that lymph nodes without metastasis-particularly tumor-draining lymph nodes-play an irreplaceable role in maintaining the host's anti-tumor immune response. Preclinical studies have found that radiation exposure to tumor-draining lymph nodes can impair the efficacy of radiotherapy combined with immunotherapy. In the surgical field, this shift in understanding has given rise to an important clinical question: in radical esophagectomy for esophageal cancer, is it possible to maximally preserve non-metastatic normal lymph nodes while ensuring complete removal of metastatic lymph nodes? If achievable, patients may not only benefit from reduced postoperative complications (such as chylothorax and recurrent laryngeal nerve injury) but also retain important immune organ function, providing a stronger basis for subsequent immunotherapy responses. Therefore, this study intends to conduct a multicenter, prospective, randomized controlled, non-inferiority trial in patients with cT1-3N0M0 esophageal squamous cell carcinoma who have not received neoadjuvant therapy, to evaluate the oncological safety of sentinel lymph node dissection based on the ICG near-infrared fluorescence imaging system in radical esophagectomy for esophageal cancer.
During the study, ICG will be injected around the tumor under intraoperative gastroscopy guidance, followed by tracking of fluorescent lymph nodes using a thoracoscopic near-infrared camera. Professional thoracic surgeons will group and mark these lymph nodes for intraoperative frozen pathology. If intraoperative frozen section shows negative sentinel lymph nodes, patients will be randomized 1:1 into two groups: one group will undergo esophagectomy alone without further lymph node dissection, while the other group will undergo conventional lymph node dissection plus esophagectomy. The primary objective of this study is to evaluate the non-inferiority of ICG-guided sentinel lymph node dissection compared with conventional systematic lymph node dissection in terms of 3-year disease-free survival in patients with cT1-3N0M0 esophageal squamous cell carcinoma who have not received neoadjuvant therapy, thereby validating the oncological safety of the sentinel lymph node dissection strategy.
Participants will:
- Undergo minimally invasive ESCC surgery within 2 weeks of enrollment, including the 14th day.
- Receive ICG injection around the tumor under intraoperative gastroscopy guidance during surgery.
- Have perioperative, postoperative pathology, and complication information recorded.
- Undergo standardized follow-up after surgery.
Detailed description
This study will enroll patients with cT1-3N0M0 esophageal cancer who have not received neoadjuvant therapy. If intraoperative frozen section shows negative sentinel lymph nodes, patients will be randomly assigned into two groups: the experimental group will undergo sentinel lymph node dissection only plus esophagectomy, while the control group will undergo conventional lymph node dissection plus esophagectomy. The investigators will compare the 3-year disease-free survival rate, postoperative complication rate, and other outcomes between the two groups to evaluate the oncological safety of sentinel lymph node dissection based on the ICG near-infrared fluorescence imaging system in radical esophagectomy for esophageal cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ICG-guided sentinel lymph node dissection only plus esophagectomy | Experimental | Drug: ICG-guided sentinel lymph node dissectionThe experimental group will undergo sentinel lymph node dissection only plus esophagectomy |
| ICG-guided systematic lymph node dissection plus esophagectomy | Active comparator | Drug: ICG-guided systematic lymph node dissectionThe control group will undergo conventional lymph node dissection plus esophagectomy |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Aged 18 to 75 years, regardless of gender;
- Histopathologically confirmed esophageal squamous cell carcinoma or adenocarcinoma by endoscopic biopsy (including esophagogastric junction carcinoma, Siewert type I/II);
- Preoperative clinical stage cT1-3N0M0 (based on contrast-enhanced CT ± PET-CT ± endoscopic ultrasound evaluation);
- No prior neoadjuvant therapy of any form (including chemotherapy, radiotherapy, chemoradiotherapy, immunotherapy, targeted therapy, etc.);
- Scheduled for minimally invasive radical esophagectomy (combined thoracoscopic and laparoscopic McKeown or Ivor-Lewis procedure);
Key exclusion criteria (15 listed)
- Preoperative imaging clearly indicating lymph node metastasis (cN+) or distant metastasis (cM1);
- Prior systemic or local treatment for esophageal cancer of any kind (including chemotherapy, radiotherapy, chemoradiotherapy, immunotherapy, etc.);
- Previous history of esophageal or gastric surgery (except endoscopic mucosal resection/submucosal dissection);
- History of allergy to iodine contrast agents or indocyanine green;
- Severe hepatic or renal insufficiency (Child-Pugh class B or C; serum creatinine ≥ 1.5 times the upper limit of normal);
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 |
|---|---|---|
| ICG-guided sentinel lymph node dissectionIn the experimental group, the investigators will perform only sentinel lymph node dissection and esophagectomy, without further lymph node resection. This intervention is distinguished by its de-escalated surgical approach: unlike conventional radical esophagectomy with systematic lymph node dissection, no additional lymph node stations will be removed beyond the identified sentinel lymph nodes. By preserving non-sentinel regional lymph nodes, this strategy aims to reduce surgical trauma and postoperative complications-such as chylothorax and recurrent laryngeal nerve injury-while maintaining oncological safety in patients with cT1-3N0M0 esophageal squamous cell carcinoma. | Drug | ICG-guided sentinel lymph node dissection only plus esophagectomy |
| ICG-guided systematic lymph node dissectionIn the control group, in addition to dissecting the sentinel lymph nodes, the investigators will proceed with standard two-field or three-field lymph node dissection for esophageal cancer. | Drug | ICG-guided systematic lymph node dissection plus esophagectomy |
Primary outcome
3-year Disease free survival rate
Time frame: The time from randomization to the first occurrence of any of the following events (local recurrence, regional lymph node recurrence, distant metastasis, or death from any cause), assessed up to 36 months.
3-year disease-free survival rate: defined as the time from randomization to the first occurrence of any of the following events: local recurrence, regional lymph node recurrence, distant metastasis, or death from any cause
5 secondary outcomes
Postoperative complications
Time frame: 30 days after surgery
Immune status indicators
Time frame: Baseline (day -1), post-operative day 1, day 7, and month 1.
lmmune status indicators
Time frame: Baseline (day -1), post-operative day 1, day 7, and month 1.
3-year Overall Survival rate
Time frame: 3-year after surgery
Diagnostic performance of ICG
Time frame: 7-day after surgery
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 2026.
- 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.
Bin Zheng principal investigator
Fujian Medical University Union Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ICG-guided sentinel lymph node dissection and ICG-guided systematic lymph node dissection in people with Esophageal Cancer and Sentinel Lymph Node, run by Fujian Medical University Union Hospital 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 15 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: opening soon, as of the sponsor's last update on 26 Aug 2026. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Contact Bin Zheng, M.D. (15959002753, lacustrian@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
3-year Disease free survival rate (time frame: The time from randomization to the first occurrence of any of the following events (local recurrence, regional lymph node recurrence, distant metastasis, or death from any cause), assessed up to 36 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 2026.