Esophageal CancerPhase 2BRIGHT-ESCCNCT07152678
Brachytherapy With Radiotherapy and Immunotherapy: Guided HDR Trial in Esophageal Squamous Cell Carcinoma
A Phase 2 study testing Nivolumab (240 mg) and Brachytherapy in people with Esophageal Cancer and Esophageal Squamous Cell Carcinoma, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
The goal of this clinical trial is to learn if adding high-dose-rate (HDR) brachytherapy can improve outcomes in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who have already received external beam radiotherapy (EBRT), chemotherapy, and the immune therapy drug nivolumab. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Esophageal Cancer, Esophageal Squamous Cell Carcinoma
- What is being tested?
- Nivolumab (240 mg) and Brachytherapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteTaiwan
- Study dates
- Sep 2025to Sep 2028
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age of 18-85 years, with ECOG performance 0-2.
- Locally-advanced esophageal squamous cell carcinoma with clinical stage III, IVA with biopsy proven.
- Prior treatment with EBRT (40-50.4 Gy in 20-28 fractions) and platinum + fluoropyrimidine chemotherapy, with residual or progressive disease, and deemed inoperable or unable to undergo surgery.
- No prior exposure to ICIs and had received first cycle of nivolumab after CCRT.
- Biopsy proven with PD-L1 [tumor cell (TC) ≥ 1%]
- Required at least one measurable or non-measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
- Patients with limited stage IVB disease (e.g., non-visceral lymph node metastasis) may be enrolled if the primary tumor is locally dominant and suitable for brachytherapy, based on investigator's discretion.
Who cannot join
- Current or past history of severe hypersensitivity to any other antibody products.
- Patients with any metastasis in the brain or meninx that is symptomatic or requires treatment.
- Patients with active, known or suspected autoimmune disease
- Stenosis of esophageal lumen that cannot performed brachytherapy
- Involvement of tracheal mucosa or bronchial mucosa.
- The distribution of the lesions of interest exceeds 10 cm range.
- The patient is participating in other interventional clinical trials associated with immunotherapy.
- The patient is scheduled to undergo esophagostomy.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Taiwan1 site, 1 recruiting
- Recruiting
National Taiwan University Hospital Yunlin Branch
Huwei, Yunlin County, 632
About this study
Official title: A Phase II Study of High-Dose-Rate Esophageal Brachytherapy After External Beam Radiotherapy and Nivolumab in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma
The goal of this clinical trial is to learn if adding high-dose-rate (HDR) brachytherapy can improve outcomes in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who have already received external beam radiotherapy (EBRT), chemotherapy, and the immune therapy drug nivolumab.
The main questions it aims to answer are:
Read more
- Does HDR brachytherapy reduce the chance of the cancer coming back in the esophagus or nearby areas within 12 months?
- What side effects or safety issues occur when HDR brachytherapy is given after EBRT, chemotherapy, and nivolumab?
Participants will:
- Receive 1-2 sessions of HDR brachytherapy delivered through a thin tube placed inside the esophagus, within three weeks after starting nivolumab.
- Continue nivolumab and be monitored with regular follow-up visits, imaging tests, and blood samples to check treatment response and safety.
Read the detailed description
This is a single-arm, phase II clinical trial designed to evaluate the efficacy and safety of high-dose-rate (HDR) esophageal brachytherapy in combination with external beam radiotherapy (EBRT), chemotherapy, and immune checkpoint inhibition with nivolumab in patients with locally advanced esophageal squamous cell carcinoma (ESCC).
Eligible patients include those with stage III-IVB ESCC who have previously received EBRT with concurrent platinum-fluoropyrimidine chemotherapy and who have initiated nivolumab therapy. HDR brachytherapy (5-12 Gy in 1-2 fractions) will be administered within three weeks following the start of nivolumab.
The primary endpoint is the 12-month cumulative incidence of locoregional failure. Secondary endpoints include overall survival, progression-free survival, overall response rate, disease control rate, safety and tolerability, tube-dependence-free survival, tumor-infiltrating lymphocyte density, and circulating tumor DNA dynamics.
The rationale for this trial is that HDR brachytherapy offers precise dose escalation directly to the esophageal tumor, which may improve locoregional control beyond EBRT alone. In addition, the combination of localized high-dose irradiation with systemic immune checkpoint inhibition has the potential to enhance antitumor immunity, thereby improving clinical outcomes in this high-risk population.
- Being tested
- Nivolumab (240 mg), Brachytherapy
- Keywords
- Esophageal squamous cell carcinoma, Brachytherapy, Immune checkpoint inhibitor, Nivolumab, Radiotherapy, Locoregional control
- Medical subject headings
- Esophageal Neoplasms, Esophageal Squamous Cell Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nivolumab (240 mg)Drug
After the first cycle of nivolumab administered in the screening phase (1st cycle), nivolumab in the study phase was administered intravenously over 30 minutes at a dose of 240 mg every 2 weeks for at least 2 doses, with 1 cycle after to first brachytherapy (2nd cycle), and 1 more cycle after to second brachytherapy (3rd cycle) if feasible. (each cycle was 2 weeks), until disease progression assessed by the investigator per RECIST version 1.1, or unacceptable toxicity.
BrachytherapyRadiation
Brachytherapy protocol starts within 3 weeks after first cycle of nivolumab was administered. After brachytherapy applicator placement, CT simulation scan(s) with dummy source in place will be done for further planning procedure, including adjustment of the applicator and 3D treatment planning. High-dose-rate (HDR) 5-Gy per fraction is delivered to the gross tumor volume (GTV) of esophageal tumor(s), second treatment if applicable will be finished within 2 weeks after the first fraction, a total of 5-12 Gy in 1-2 fractions will be delivered. GTV coverage D90 should equal 100% of prescription. Efforts should be made to spare the adjacent normal organ and to avoid hot spot on normal esophageal mucosa. It is NOT allowed to give concurrent chemotherapy on the days of HDR brachytherapy.
| Study group | Role | What they receive |
|---|---|---|
| Add-on of intraluminal brachytherapy with applicator | Experimental | Brachytherapy protocol starts within 3 weeks after first cycle of immunotherapy administered (This is "week 1"). High-dose-rate (HDR) 5-6 Gy per fraction is delivered to GTV of esophageal tumor(s), second treatment if applicable will be finished within 2 weeks after the first fraction, a total of 5-12 Gy in 1-2 fractions will be delivered. GTV coverage D90 should equal 100% of prescription. It is NOT allowed to give concurrent chemotherapy on the days of HDR brachytherapy. Receives: Drug: Nivolumab (240 mg); Radiation: Brachytherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative incidence of locoregional failure at 12 months
The proportion of patients who develop tumor recurrence or persistence in the esophagus or regional lymph nodes, as assessed by central review using endoscopy, CT and/or PET according to RECIST v1.1 and iRECIST criteria.
Measured: 12 months from initiation of HDR brachytherapy
Secondary outcomes (10)
Overall Response Rate (ORR)
Percentage of patients achieving complete response or partial response as best overall response, assessed by investigators per RECIST v1.1 and iRECIST.
Measured: Up to 24 months
Overall Survival (OS)
Time from enrollment to death from any cause.
Measured: Up to 24 months
Progression-Free Survival (PFS)
Time from enrollment to first documented tumor progression or death, whichever occurs first.
Measured: Up to 24 months
Disease Control Rate (DCR)
Percentage of patients achieving complete response, partial response, or stable disease, as best overall response per RECIST v1.1/iRECIST.
Measured: Up to 24 months
Duration of Response (DoR)
Time from the first documentation of complete or partial response to the first documented tumor progression or death.
Measured: Up to 24 months
Cumulative incidence of distant failure
Proportion of patients developing new distant metastases over the study period, accounting for competing risks.
Measured: Up to 24 months
Safety and tolerability
Incidence and severity of adverse events (AEs), serious adverse events (SAEs), and immune-related adverse events, graded according to CTCAE v5.0.
Measured: From first study treatment through 90 days after last dose and up to 24 months for late effect
Tube-dependence-free survival
Proportion of patients who remain alive without requiring feeding tube support (e.g., nasogastric or jejunostomy tube) for nutrition.
Measured: Up to 24 months
Circulating tumor DNA (ctDNA) dynamics
Change in ctDNA levels measured at baseline and during follow-up as an indicator of treatment response and disease progression.
Measured: Baseline and up to 24 months
Tumor-infiltrating lymphocyte (TIL) density
Change in tumor-infiltrating lymphocyte density in tumor biopsy samples collected before and after HDR brachytherapy.
Measured: Baseline to up to 12 weeks after HDR brachytherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2025
- Study startSep 2025 (estimated)
- Primary completionSep 2027 (estimated)
- Study completionSep 2028 (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 National Taiwan University 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yen-Ting Liu, MD, Principal investigator, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07152678
- Sponsor's protocol ID
- 202505130MIND
- Acronym
- BRIGHT-ESCC
- Status last verified
- Jul 2025
- First submitted
- 26 Aug 2025
- Last updated
- 3 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of High-Dose-Rate Esophageal Brachytherapy After External Beam Radiotherapy and Nivolumab in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT07152678
- Acronym / sponsor ID
- BRIGHT-ESCC / 202505130MIND
- Keywords
- Esophageal squamous cell carcinoma, Brachytherapy, Immune checkpoint inhibitor, Nivolumab, Radiotherapy, Locoregional control
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- Sep 2025 (estimated)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Sep 2028 (estimated)
- First posted
- 3 Sep 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.
The goal of this clinical trial is to learn if adding high-dose-rate (HDR) brachytherapy can improve outcomes in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who have already received external beam radiotherapy (EBRT), chemotherapy, and the immune therapy drug nivolumab.
The main questions it aims to answer are:
- Does HDR brachytherapy reduce the chance of the cancer coming back in the esophagus or nearby areas within 12 months?
- What side effects or safety issues occur when HDR brachytherapy is given after EBRT, chemotherapy, and nivolumab?
Participants will:
- Receive 1-2 sessions of HDR brachytherapy delivered through a thin tube placed inside the esophagus, within three weeks after starting nivolumab.
- Continue nivolumab and be monitored with regular follow-up visits, imaging tests, and blood samples to check treatment response and safety.
Detailed description
This is a single-arm, phase II clinical trial designed to evaluate the efficacy and safety of high-dose-rate (HDR) esophageal brachytherapy in combination with external beam radiotherapy (EBRT), chemotherapy, and immune checkpoint inhibition with nivolumab in patients with locally advanced esophageal squamous cell carcinoma (ESCC).
Eligible patients include those with stage III-IVB ESCC who have previously received EBRT with concurrent platinum-fluoropyrimidine chemotherapy and who have initiated nivolumab therapy. HDR brachytherapy (5-12 Gy in 1-2 fractions) will be administered within three weeks following the start of nivolumab.
The primary endpoint is the 12-month cumulative incidence of locoregional failure. Secondary endpoints include overall survival, progression-free survival, overall response rate, disease control rate, safety and tolerability, tube-dependence-free survival, tumor-infiltrating lymphocyte density, and circulating tumor DNA dynamics.
The rationale for this trial is that HDR brachytherapy offers precise dose escalation directly to the esophageal tumor, which may improve locoregional control beyond EBRT alone. In addition, the combination of localized high-dose irradiation with systemic immune checkpoint inhibition has the potential to enhance antitumor immunity, thereby improving clinical outcomes in this high-risk population.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Add-on of intraluminal brachytherapy with applicator | Experimental | Drug: Nivolumab (240 mg), Radiation: BrachytherapyBrachytherapy protocol starts within 3 weeks after first cycle of immunotherapy administered (This is "week 1"). High-dose-rate (HDR) 5-6 Gy per fraction is delivered to GTV of esophageal tumor(s), second treatment if applicable will be finished within 2 weeks after the first fraction, a total of 5-12 Gy in 1-2 fractions will be delivered. GTV coverage D90 should equal 100% of prescription. It is NOT allowed to give concurrent chemotherapy on the days of HDR brachytherapy. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age of 18-85 years, with ECOG performance 0-2.
- Locally-advanced esophageal squamous cell carcinoma with clinical stage III, IVA with biopsy proven.
- Prior treatment with EBRT (40-50.4 Gy in 20-28 fractions) and platinum + fluoropyrimidine chemotherapy, with residual or progressive disease, and deemed inoperable or unable to undergo surgery.
- No prior exposure to ICIs and had received first cycle of nivolumab after CCRT.
- Biopsy proven with PD-L1 [tumor cell (TC) ≥ 1%]
Key exclusion criteria (8 listed)
- Current or past history of severe hypersensitivity to any other antibody products.
- Patients with any metastasis in the brain or meninx that is symptomatic or requires treatment.
- Patients with active, known or suspected autoimmune disease
- Stenosis of esophageal lumen that cannot performed brachytherapy
- Involvement of tracheal mucosa or bronchial mucosa.
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 |
|---|---|---|
| Nivolumab (240 mg)After the first cycle of nivolumab administered in the screening phase (1st cycle), nivolumab in the study phase was administered intravenously over 30 minutes at a dose of 240 mg every 2 weeks for at least 2 doses, with 1 cycle after to first brachytherapy (2nd cycle), and 1 more cycle after to second brachytherapy (3rd cycle) if feasible. (each cycle was 2 weeks), until disease progression assessed by the investigator per RECIST version 1.1, or unacceptable toxicity. | Drug | Add-on of intraluminal brachytherapy with applicator |
| BrachytherapyBrachytherapy protocol starts within 3 weeks after first cycle of nivolumab was administered. After brachytherapy applicator placement, CT simulation scan(s) with dummy source in place will be done for further planning procedure, including adjustment of the applicator and 3D treatment planning. High-dose-rate (HDR) 5-Gy per fraction is delivered to the gross tumor volume (GTV) of esophageal tumor(s), second treatment if applicable will be finished within 2 weeks after the first fraction, a total of 5-12 Gy in 1-2 fractions will be delivered. GTV coverage D90 should equal 100% of prescription. Efforts should be made to spare the adjacent normal organ and to avoid hot spot on normal esophageal mucosa. It is NOT allowed to give concurrent chemotherapy on the days of HDR brachytherapy. | Radiation | Add-on of intraluminal brachytherapy with applicator |
Primary outcome
Cumulative incidence of locoregional failure at 12 months
Time frame: 12 months from initiation of HDR brachytherapy
The proportion of patients who develop tumor recurrence or persistence in the esophagus or regional lymph nodes, as assessed by central review using endoscopy, CT and/or PET according to RECIST v1.1 and iRECIST criteria.
10 secondary outcomes
Overall Response Rate (ORR)
Time frame: Up to 24 months
Overall Survival (OS)
Time frame: Up to 24 months
Progression-Free Survival (PFS)
Time frame: Up to 24 months
Disease Control Rate (DCR)
Time frame: Up to 24 months
Duration of Response (DoR)
Time frame: Up to 24 months
Cumulative incidence of distant failure
Time frame: Up to 24 months
Safety and tolerability
Time frame: From first study treatment through 90 days after last dose and up to 24 months for late effect
Tube-dependence-free survival
Time frame: Up to 24 months
Circulating tumor DNA (ctDNA) dynamics
Time frame: Baseline and up to 24 months
Tumor-infiltrating lymphocyte (TIL) density
Time frame: Baseline to up to 12 weeks after HDR brachytherapy
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 3 Sep 2025.
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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.
Yen-Ting Liu, MD principal investigator
National Taiwan University Hospital
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 Nivolumab (240 mg) and Brachytherapy in people with Esophageal Cancer and Esophageal Squamous Cell Carcinoma, run by National Taiwan University Hospital at 1 site in Taiwan.
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 7 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: looking for participants now, as of the sponsor's last update on 3 Sep 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 Taiwan. 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?
Contact Yen-Ting Liu, MD (+886-2-33663366 ext. 24130, nickliucool@ntuh.gov.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cumulative incidence of locoregional failure at 12 months (time frame: 12 months from initiation of HDR brachytherapy). 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 3 Sep 2025.