A Phase 2 interventional study of Tislelizumab and Low-dose radiotherapy in Esophageal Squamous Cell Carcinoma, sponsored by Sichuan University. Recruiting at 1 site in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2025-06-06.
Sponsored by Sichuan University · Phase 2, Interventional, and Treatment
This study aims to investigate the efficacy and safety of low-dose radiation combined with neoadjuvant chemotherapy and immunotherapy in the treatment of locally advanced thoracic esophageal squamous cell carcinoma. By reducing the radiation dose from 40 Gy in 20 fractions to 4 Gy in 2 fractions, the goal is to lessen the adverse reactions caused by radiotherapy. Additionally, the study explores whether low-dose radiation therapy can promote the cross-presentation of tumor-specific antigens and increase lymphocyte infiltration into the tumor site. Study also examines whether this approach can enhance tumor-specific immune responses, thereby potentially improving the efficacy of immune checkpoint inhibitors.
According to 2020 GLOBOCAN data, esophageal cancer ranks fifth in incidence among all malignant tumors in China, with new cases reaching 324,000 and annual deaths at 301,000. These figures indicate a significant burden of esophageal cancer in China, accounting for 55% of esophageal cancer cases globally. Unlike in Western countries, most esophageal cancer patients in China have squamous cell carcinoma, and 40% are diagnosed at an advanced stage. Surgery is a key treatment for locally advanced esophageal cancer, but patients may achieve better clinical outcomes if they receive neoadjuvant therapy before surgery. However, the prognosis for these patients remains relatively poor. From 2009 to 2015, the overall 5-year relative survival rate for esophageal cancer was 21.4%, with local tumors at 46.7%, regional metastasis at 25.1%, and distant metastasis at only 4.8%.
In recent years, immunotherapy has shown significant survival benefits in patients with advanced esophageal cancer. Immuno-chemotherapy has now become the standard first-line treatment for advanced esophageal cancer. Currently, the introduction of immunotherapy as neoadjuvant treatment in locally advanced esophageal cancer is a highly regarded research area. Many studies are underway involving the combined application of neoadjuvant chemotherapy and immunotherapy, as well as neoadjuvant chemoradiotherapy and immunotherapy. Regarding safety, tislelizumab is similar to foreign similar drugs, mostly causing grade 1-2 adverse reactions, and is within a controllable range. Our center's previous research results have shown that tislelizumab can be used as a neoadjuvant immunotherapy drug for esophageal squamous cell carcinoma, with good perioperative safety.
It is worth noting that recent study reports indicate that the pathological complete response (PCR) rate of neoadjuvant chemotherapy combined with immunotherapy in small sample studies ranges from 17% to 22%, showing significant heterogeneity. Recently, Chinese scholars published a study in the international authoritative academic journal "Nature Medicine," indicating that using a PD-L1 antibody for immunotherapy combined with surgery, although the PCR rate was only 8%, the long-term survival effect was comparable to traditional chemoradiotherapy. This further proves that compared to traditional neoadjuvant chemoradiotherapy, neoadjuvant immunotherapy has broad development potential. However, the local control effects of immunotherapy alone or combined with chemotherapy are still unsatisfactory, which may affect the radical outcome of surgery and the long-term survival of patients. Therefore, combining more effective local treatment methods with immunotherapy is undoubtedly a more promising treatment option.
Low-dose radiotherapy (LDRT) is generally defined as a treatment not exceeding 2 Gy per session, totaling no more than 10 Gy, and is considered a non-ablative treatment [13]. The low toxicity of low-dose radiotherapy makes it a treatment option for those not suitable for body-targeted radiation therapy. Furthermore, although low-dose radiotherapy does not directly kill cancer cells, it can promote tumor regression by readjusting the tumor immune microenvironment.
Low-dose radiotherapy damages cell DNA, causing previously hidden or difficult-to-recognize tumor antigens to be exposed on the cell surface. This change promotes the cross-presentation of tumor-specific antigens, increases lymphocyte infiltration into the tumor site, enhances tumor-specific immune responses, and further improves the efficacy of immune checkpoint inhibitors. Preoperative immunotherapy can activate the patient's immune system, enabling it to recognize tumor antigens and establish immune memory. This allows the immune system to continue to function in immune surveillance after the surgical removal of the tumor. Currently, the main focus of clinical research is on how to maximize the synergistic effects between different treatment modalities to achieve the best survival outcomes for patients with locally advanced esophageal cancer while minimizing treatment side effects.
This study is a phase IIa clinical trial focusing on preliminary efficacy and safety. The study proposes a comprehensive treatment of neoadjuvant low-dose radiotherapy combined with chemotherapy and immunotherapy (chemoradiotherapy plus immunotherapy). By reducing the radiotherapy dose, the aim is to enhance local control efficacy while minimizing adverse reactions caused by the combined treatment regimen.
The plan involves neoadjuvant low-dose radiotherapy combined with chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma, with radiotherapy doses adjusted from 40 Gy/20 fractions to 4 Gy/2 fractions, 6 Gy/3 fractions, or 8 Gy/4 fractions. The study aims to evaluate the efficacy and safety of this treatment model, providing further evidence for neoadjuvant treatment strategies in locally advanced esophageal cancer patients.
Additionally, exploratory analyses will be conducted on preoperative and postoperative tissue and blood samples to understand the impact of preoperative low-dose radiotherapy combined with immunotherapy on the immune microenvironment of esophageal cancer, identify appropriate biomarkers, and determine the optimal beneficiary population.
6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.
This study's planned enrollment of 30 is below the median of 45 across 5,170 interventional studies indexed under Carcinoma.
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During the neoadjuvant treatment phase, patients will undergo two cycles of low-dose radiotherapy, combined with chemotherapy and immunotherapy, each cycle lasting 21 days. The specific treatment protocol is as follows: D1/2: Low-dose radiotherapy (4 Gy/2f) D3: Tislelizumab, fixed dose of 200 mg; Nab-paclitaxel 260 mg/m2; Cisplatin 75 mg/m2. The interval between radiotherapy and chemotherapy should not exceed 3 days. Drug infusions follow the sequence of tislelizumab → nab-paclitaxel → cisplatin/carboplatin, with at least a 30-minute interval between each infusion. At the end of the neoadjuvant treatment, patients will undergo surgical treatment 6-8 weeks after the last treatment session.
Drug: Tislelizumab · Radiation: Low-dose radiotherapy · Drug: Nab-paclitaxel · Drug: Cisplatin
During the neoadjuvant treatment phase, patients will undergo two cycles of low-dose radiotherapy, combined with chemotherapy and immunotherapy, each cycle lasting 21 days. The specific treatment protocol is as follows: D1/2/3: Low-dose radiotherapy (6 Gy/3f) D4: Tislelizumab, fixed dose of 200 mg; Nab-paclitaxel 260 mg/m2; Cisplatin 75 mg/m2. The interval between radiotherapy and chemotherapy should not exceed 3 days. Drug infusions follow the sequence of tislelizumab → nab-paclitaxel → cisplatin/carboplatin, with at least a 30-minute interval between each infusion. At the end of the neoadjuvant treatment, patients will undergo surgical treatment 6-8 weeks after the last treatment session.
Drug: Tislelizumab · Radiation: Low-dose radiotherapy · Drug: Nab-paclitaxel · Drug: Cisplatin
During the neoadjuvant treatment phase, patients will undergo two cycles of low-dose radiotherapy, combined with chemotherapy and immunotherapy, each cycle lasting 21 days. The specific treatment protocol is as follows: D1/2/3/4: Low-dose radiotherapy (8 Gy/4f) D5: Tislelizumab, fixed dose of 200 mg; Nab-paclitaxel 260 mg/m2; Cisplatin 75 mg/m2. The interval between radiotherapy and chemotherapy should not exceed 3 days. Drug infusions follow the sequence of tislelizumab → nab-paclitaxel → cisplatin/carboplatin, with at least a 30-minute interval between each infusion. At the end of the neoadjuvant treatment, patients will undergo surgical treatment 6-8 weeks after the last treatment session.
Drug: Tislelizumab · Radiation: Low-dose radiotherapy · Drug: Nab-paclitaxel · Drug: Cisplatin
Patients will undergo two cycles of immunotherapy, each cycle lasting 21 days. Day 3 and Day 24: Tislelizumab, fixed dose of 200 mg
Also known as: Tislelizumab, fixed dose of 200 mg
Patients will undergo two cycles of low-dose radiotherapy. Day 1/2 and Day 22/23: Low-dose radiotherapy (8 Gy/4f)
Also known as: Low-dose radiotherapy (8 Gy/4f)
Patients will undergo two cycles of chemotherapy. Day 3 and Day 24: Nab-paclitaxel 260 mg/m2
Also known as: Nab-paclitaxel 260 mg/m2
Patients will undergo two cycles of chemotherapy. Day 3 and Day 24: Cisplatin 75 mg/m2.
Also known as: Cisplatin 75 mg/m2
Pathologic complete response
The proportion of subjects with 0% of surviving tumor cells remaining in the primary tumor and in the sampled lymph nodes as evaluated by histology.
Time frame: Immediately after the surgery
Major pathological response
Complete response (CR) + partial response (PR) was evaluated by RECIST 1.1 criteria Complete response (CR) + partial response (PR) was evaluated by RECIST 1.1 criteria Complete response (CR) + partial response (PR) was evaluated by RECIST 1.1 criteria
Time frame: Immediately after the surgery
R0 rate
Intraoperative evaluation
Time frame: During the surgery
1/2 year event-free survival
The time of enrollment (i.e., signing the ICF) until the following events: any disease progression resulting in surgery not being performed, disease progression or recurrence after surgery, disease progression in patients without surgery, or death from any cause
Time frame: 2 years
Overall Response Rate
Complete response (CR) + partial response (PR) was evaluated by RECIST 1.1 criteria
Time frame: Immediately after the surgery
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Sichuan University