Combining immunotherapy with chemoradiotherapy for advanced esophageal cancer

Neoadjuvant Immunotherapy Combined With Chemoradiotherapy Versus Neoadjuvant Chemoradiotherapy for Locally Advanced Resectable Esophageal Squamous Cell Carcinoma (cII-III Stage): A Multi-center Prospective Randomized Clinical Trial

This study is testing if adding a new immunotherapy drug to standard treatment can help people with advanced esophageal cancer do better before surgery.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 176 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shanghai Zhongshan Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, Tislelizumab
• Locations: 1 site (Shanghai)
• Trial ID: NCT04973306 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and effectiveness of combining the anti-PD-1 antibody Tislelizumab with neoadjuvant chemoradiotherapy in patients with locally advanced resectable esophageal squamous cell carcinoma. A total of 476 patients will be randomly assigned to receive either the combination treatment or standard neoadjuvant chemoradiotherapy. The study aims to compare the outcomes, safety, and prognosis between these two treatment regimens. It is a prospective randomized phase II and III trial conducted across multiple hospitals in China.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with histologically confirmed stage II-III esophageal squamous cell carcinoma.

Not a fit: Patients with other types of esophageal cancer or those with significant comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes and survival rates for patients with advanced esophageal cancer.

How similar studies have performed: Other studies have shown promising results with immunotherapy in combination with chemoradiotherapy for various cancers, suggesting potential success for this approach.

Eligibility criteria

Inclusion Criteria:

1. Histologically-confirmed esophageal squamous cell carcinoma and whose tissue samples were taken before treatment;
2. Tumors of the esophagus are located in the thoracic cavity;
3. Pre-treatment stage as clinical II-III (AJCC/UICC 8th Edition)
4. Age is between 18 years and 75 years;
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and expected survival time ≥12 months;
6. Adequate cardiac function. All patients should perform ECG, and those with a cardiac history or ECG abnormality should perform echocardiography with the left ventricular ejection fraction \> 50 %;
7. Adequate respiratory function with FEV1≥1.2L, FEV1%≥50% and DLCO≥50% shown in pulmonary function tests ;
8. Adequate bone marrow function (White Blood Cells \>4x10\^9 /L; Neutrophil \>2.0×10\^9 /L; Hemoglobin \> 90 g/L; platelets\>100x10\^9 /L);
9. Adequate liver function (Total bilirubin \<1.5x Upper Level of Normal (ULN); Aspartate transaminase(AST) and Alanine transaminase (ALT) \<1.5x ULN);
10. Adequate renal function (Glomerular filtration rate (CCr) \>60 ml/min; serum creatinine (SCr) ≤120 µmol/L);
11. The patient has provided written informed consent and is able to understand and comply with the study;

Exclusion Criteria:

Exclusion Criteria associated with Cancer:

1. Patients with histological non-squamous cell carcinoma;
2. Patients with advanced non-operable or metastatic esophageal cancer;
3. Pre-treatment stage as cM+, cN3 or cT4b(non-curatively-resectable verified by the local surgical investigator, AJCC/UICC 8th Edition) or cTis-1a, cT1bN0;
4. Patients with another previous or current malignant disease which is likely to interfere with treatment or the assessment of response in the judgement of the local surgical investigator;
5. Patients who have received or are receiving other chemotherapy, radiotherapy or targeted therapy;

   Other Exclusion Criteria:
6. Patients with autoimmune diseases history;
7. Recently or currently taking Glucocorticoids or Immunosuppressants;
8. Patients who underwent immunotherapy in the past;
9. Allergy to any antibody drugs or allergy to Paclitaxel and Carboplatin.
10. Past or currently suffering from chronic or recurrent autoimmune diseases;
11. Patients with active infection of immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); HIV seropositivity; HBV DNA or HCV RNA positive;
12. Patients with organ transplantation (including autologous bone marrow transplantation and peripheral stem cell transplantation);
13. Patients with severe systematic intercurrent disease, such as active infection or poorly controlled diabetes; coagulation disorders; hemorrhagic tendency or under treatment of thrombolysis or anticoagulant therapy;
14. Any patient with a significant medical condition which is thought unlikely to tolerate the therapies. Such as cardiac disease (e.g. symptomatic coronary artery disease or myocardial infarction within last 12 months), clinically-significant lung disease, clinically-significant bone marrow, liver, renal function disorder;
15. Pregnant or lactating women and fertile women who will not be using contraception during the trial;
16. Participation in another intervention clinical trial with interference to the chemotherapeutic or chemoradiotherapeutic intervention during this study or during the last 30 days prior to informed consent;
17. Expected lack of compliance with the protocol.

Where this trial is running

Shanghai

• Shanghai Zhongshan Hospital — Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Lijie Tan, MD — Shanghai Zhongshan Hospital

Conditions Esophageal Squamous Cell Carcinoma Stage II; Esophageal Squamous Cell Carcinoma Stage III; Esophageal Squamous Cell Carcinoma