Esophagus CancerPhase 2NEXUS-2NCT06430658
Neoadjuvant Comprehensive Treatment for Unresectable Esophageal Cancer
A Phase 2 study testing Tislelizumab (BGB-A317) with chemoradiotherapy in people with Esophagus Cancer, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 1 site in China.
Trial summary
Patients diagnosed with locally advanced esophageal squamous cell carcinoma (ESCC) that is deemed unresectable face a bleak prognosis. Recent phase 1/2 studies have demonstrated the efficacy and safety of augmenting neoadjuvant concurrent chemoradiotherapy with immunotherapy in treating resectable ESCC. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Esophagus Cancer
- What is being tested?
- Tislelizumab (BGB-A317) with chemoradiotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteChina
- Study dates
- 1 Apr 2024to 31 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed sorely ESCC without other histology subtypes.
- Thoracic esophageal cancer.
- No prior anti-cancer treatment, including but not limited to surgery, radiotherapy, chemotherapy, targeted therapy, or immunotherapy.
- Borderline unresectable locally advanced ESCC deemed by investigators as suspicious of but not confirmed T4b according to the American Joint Committee on Cancer (AJCC) 8th edition staging classification or extracapsular lymph node involvement (ELNI).
- The Karnofsky Performance Scale (KPS) ≥70.
- Normal primary organ functions, including but not limited to hemoglobin (Hb) ≥ 100g/L; white blood cell (WBC) ≥ 3.5×10*9/L; neutrophil count (NEUT) ≥ 1.5×10*9/L; platelets (PLT) ≥ 100×10*9/L; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5×UNL; total bilirubin (TBIL) ≤ 1.5×UNL; creatinine ≤ 1.5UNL; blood urea nitrogen (BUN) ≤ 1.0×UNL.
Who cannot join
- Synchronous and metachronous primary malignancies in but not limited to the upper aerodigestive tract, except for cured basal cell carcinoma of the skin and carcinoma in situ of the cervix.
- Patients have undergone any type of anti-cancer treatment.
- Baseline clinical stage M1 per AJCC 8th edition of staging classification, including supraclavicular lymph node metastases.
- Investigators assessed major vessel involvement with high-risk hemorrhage.
- A higher probability of esophageal perforation during conversion therapy.
- Active infectious diseases, including but not limited to tuberculosis, hepatitis B virus, or hepatitis C virus.
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- Allergic to anti-cancer agents, including but not limited to anti-PD-1 or chemotherapy agents.
- Given cardiopulmonary dysfunction, patients can not tolerate conversion therapy or surgery.
- Pregnant or lactating women and women of childbearing potential who lacked effective contraception.
- Non-compliance with the inclusion criteria judged by investigators.
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, 1 recruiting
- Recruiting
Department of Radiation Oncology, Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
Beijing, 100021
Xin Wang, MD, +861013311583220, beryl_wx2000@163.com
About this study
Official title: NEoadjuvant Total RX for Borderline Unresectable Esophageal Squamous Cell Carcinoma: a Prospective Randomized, Three-Arm, Open-Label Phase II Trial (NEXUS-2)
Patients diagnosed with locally advanced esophageal squamous cell carcinoma (ESCC) that is deemed unresectable face a bleak prognosis. Recent phase 1/2 studies have demonstrated the efficacy and safety of augmenting neoadjuvant concurrent chemoradiotherapy with immunotherapy in treating resectable ESCC. The present study is a prospective, 3-arm, randomized trial that seeks to evaluate the efficacy of diverse conversion therapy modalities in patients with unresectable ESCC. The study objectives include R0 resection rate, treatment-related adverse events, morbidity and mortality, 1-year progression-free survival (PFS), and 1-year overall survival (OS) rates.
Tislelizumab is a humanized IgG4 monoclonal antibody with high affinity/specificity for programmed cell death protein 1 (PD-1). Tislelizumab was specifically engineered to minimize binding to FcɤR on macrophages, thereby abrogating antibody-dependent phagocytosis, a potential mechanism of T-cell clearance and resistance to anti-PD-1 therapy.
This trial will provide valuable insights into the effectiveness of the three conversion therapy modalities and help to inform clinical decision-making for patients with unresectable locally advanced ESCC.
- Conditions
- Esophagus Cancer
- Being tested
- Tislelizumab (BGB-A317) with chemoradiotherapy
- Keywords
- Esophagus Cancer, Chemoradiotherapy, conversion surgery, immunotherapy
- Medical subject headings
- Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tislelizumab (BGB-A317) with chemoradiotherapyCombination product
Different sequences and methods of treatment to convert surgery
| Study group | Role | What they receive |
|---|---|---|
| ChemoRT+Immuno | Experimental | Surgery was evaluated after chemoradiotherapy (40-41.4Gy/1.8-2Gy/20-23 fractions) followed by two cycles of chemotherapy and immunotherapy.For inoperable patients, immunotherapy was used as maintenance therapy Receives: Combination Product: Tislelizumab (BGB-A317) with chemoradiotherapy |
| Immuno+ChemoRT | Experimental | Surgery was evaluated after two cycles of chemotherapy and immunotherapy followed by chemoradiotherapy(40-41.4Gy/1.8-2Gy/20-23 fractions).For inoperable patients, immunotherapy was used as maintenance therapy Receives: Combination Product: Tislelizumab (BGB-A317) with chemoradiotherapy |
| ChemoRT | Active comparator | Surgery was evaluated after concurrent definitive chemoradiotherapy (50-50.4Gy/1.8-2Gy/25-28fractions) .For inoperable patients, immunotherapy was used as maintenance therapy Receives: Combination Product: Tislelizumab (BGB-A317) with chemoradiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
R0 resection rate
Minimal distance tumor/circumferential resection margin (CRM) > 1 mm.
Measured: 4 months
Secondary outcomes (6)
1-year OS rate
Defined as the proportion of patients still alive within one year from treatment initiation.
Measured: 1 year after all treatment
1-year PFS
Defined as the proportion of patients without disease progression or death within one year from treatment initiation.
Measured: 1 year after all treatment
Positive rate of circulating tumor DNA (ctDNA) in minimal residual disease (MRD) before and after neoadjuvant treatment and its correlation with the pathological response and disease progression during surveilance
To investigate whether ctDNA variation can be used for MRD predicting incidence of pathological incidence and monitoring tumor progression after surgery
Measured: 6 month
Incidence of Treatment-Emergent Adverse Events
Adverse event during chemoRT or immunotherapy
Measured: 4 month
Pathological response rate
Measured: 4 month
Postoperative complications
Measured: 4 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2024
- Study start1 Apr 2024
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Esophagus CancerStudies of the same condition, open and under way.
- More trials run by Cancer Institute and Hospital, Chinese Academy of Medical SciencesThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, YIN LI, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06430658
- Sponsor's protocol ID
- NEXUS-2
- Acronym
- NEXUS-2
- Status last verified
- Dec 2024
- First submitted
- 13 May 2024
- Last updated
- 27 Dec 2024
- 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 27 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NEoadjuvant Total RX for Borderline Unresectable Esophageal Squamous Cell Carcinoma: a Prospective Randomized, Three-Arm, Open-Label Phase II Trial (NEXUS-2)
- ClinicalTrials.gov ID
- NCT06430658
- Acronym / sponsor ID
- NEXUS-2 / NEXUS-2
- Conditions
- Esophagus Cancer
- Keywords
- Esophagus Cancer, Chemoradiotherapy, conversion surgery, immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Cancer Institute and Hospital, Chinese Academy of Medical SciencesUniversity, hospital or other
- Study start
- 1 Apr 2024 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 28 May 2024 (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.
Patients diagnosed with locally advanced esophageal squamous cell carcinoma (ESCC) that is deemed unresectable face a bleak prognosis. Recent phase 1/2 studies have demonstrated the efficacy and safety of augmenting neoadjuvant concurrent chemoradiotherapy with immunotherapy in treating resectable ESCC. The present study is a prospective, 3-arm, randomized trial that seeks to evaluate the efficacy of diverse conversion therapy modalities in patients with unresectable ESCC. The study objectives include R0 resection rate, treatment-related adverse events, morbidity and mortality, 1-year progression-free survival (PFS), and 1-year overall survival (OS) rates.
Tislelizumab is a humanized IgG4 monoclonal antibody with high affinity/specificity for programmed cell death protein 1 (PD-1). Tislelizumab was specifically engineered to minimize binding to FcɤR on macrophages, thereby abrogating antibody-dependent phagocytosis, a potential mechanism of T-cell clearance and resistance to anti-PD-1 therapy.
This trial will provide valuable insights into the effectiveness of the three conversion therapy modalities and help to inform clinical decision-making for patients with unresectable locally advanced ESCC.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ChemoRT+Immuno | Experimental | Combination Product: Tislelizumab (BGB-A317) with chemoradiotherapySurgery was evaluated after chemoradiotherapy (40-41.4Gy/1.8-2Gy/20-23 fractions) followed by two cycles of chemotherapy and immunotherapy.For inoperable patients, immunotherapy was used as maintenance therapy |
| Immuno+ChemoRT | Experimental | Combination Product: Tislelizumab (BGB-A317) with chemoradiotherapySurgery was evaluated after two cycles of chemotherapy and immunotherapy followed by chemoradiotherapy(40-41.4Gy/1.8-2Gy/20-23 fractions).For inoperable patients, immunotherapy was used as maintenance therapy |
| ChemoRT | Active comparator | Combination Product: Tislelizumab (BGB-A317) with chemoradiotherapySurgery was evaluated after concurrent definitive chemoradiotherapy (50-50.4Gy/1.8-2Gy/25-28fractions) .For inoperable patients, immunotherapy was used as maintenance therapy |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Histologically confirmed sorely ESCC without other histology subtypes.
- Thoracic esophageal cancer.
- No prior anti-cancer treatment, including but not limited to surgery, radiotherapy, chemotherapy, targeted therapy, or immunotherapy.
- Borderline unresectable locally advanced ESCC deemed by investigators as suspicious of but not confirmed T4b according to the American Joint Committee on Cancer (AJCC) 8th edition staging classification or extracapsular lymph node involvement (ELNI).
- The Karnofsky Performance Scale (KPS) ≥70.
Key exclusion criteria (10 listed)
- Synchronous and metachronous primary malignancies in but not limited to the upper aerodigestive tract, except for cured basal cell carcinoma of the skin and carcinoma in situ of the cervix.
- Patients have undergone any type of anti-cancer treatment.
- Baseline clinical stage M1 per AJCC 8th edition of staging classification, including supraclavicular lymph node metastases.
- Investigators assessed major vessel involvement with high-risk hemorrhage.
- A higher probability of esophageal perforation during conversion therapy.
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 |
|---|---|---|
| Tislelizumab (BGB-A317) with chemoradiotherapyDifferent sequences and methods of treatment to convert surgery | Combination product | ChemoRT, ChemoRT+Immuno, Immuno+ChemoRT |
Primary outcome
R0 resection rate
Time frame: 4 months
Minimal distance tumor/circumferential resection margin (CRM) > 1 mm.
6 secondary outcomes
1-year OS rate
Time frame: 1 year after all treatment
1-year PFS
Time frame: 1 year after all treatment
Positive rate of circulating tumor DNA (ctDNA) in minimal residual disease (MRD) before and after neoadjuvant treatment and its correlation with the pathological response and disease progression during surveilance
Time frame: 6 month
Incidence of Treatment-Emergent Adverse Events
Time frame: 4 month
Pathological response rate
Time frame: 4 month
Postoperative complications
Time frame: 4 month
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 27 Dec 2024.
- 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.
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 Tislelizumab (BGB-A317) with chemoradiotherapy in people with Esophagus Cancer, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences 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 6 inclusion and 10 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 27 Dec 2024. 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?
Contact Xin Wang, Doctor (13311583220, beryl_wx2000@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
R0 resection rate (time frame: 4 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 27 Dec 2024.