Early Response-guided Sequential Radiotherapy After Chemoimmunotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma

NCT07721103 | Not Yet Recruiting Phase 2

• 1 other identifier: E20260722
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

Esophageal squamous cell carcinoma (ESCC) is a common and aggressive malignancy with poor prognosis, particularly in patients with locally advanced disease. Neoadjuvant chemoimmunotherapy has shown promising antitumor activity and may improve pathological response; however, a proportion of patients achieve only stable disease (SD) or progressive disease (PD) after initial treatment and may have limited benefit from proceeding directly to surgery. This prospective, single-center, phase II clinical study aims to evaluate an early response-guided sequential selective radiotherapy strategy after neoadjuvant chemoimmunotherapy in patients with locally advanced, resectable ESCC. Patients will initially receive neoadjuvant chemotherapy combined with PD-1 inhibitor therapy. Based on radiological response assessment, patients with major response (complete response or partial response) will proceed directly to radical surgery, whereas patients with insufficient response (stable disease or progressive disease but still considered resectable) will receive sequential chemoradiotherapy followed by surgery. The study aims to assess the safety and efficacy of this individualized treatment strategy, with primary evaluation focusing on pathological response, surgical outcomes, and treatment-related adverse events. Exploratory analyses will investigate potential biomarkers associated with treatment response and prognosis.

Conditions

Esophageal Squamous Cell Carcinoma (ESCC)

Keywords

Locally advanced esophageal cancer; Neoadjuvant therapy; Adaptive treatment strategy; Response-guided therapy

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability Equivalent Major Pathological Response Rate (ITT-MPR)

  Up to approximately 1.5 years

Secondary Outcomes (10)

• R0 Resection Rate

  At the time of surgery after completion of neoadjuvant treatment

• Surgical Completion Rate

  At the time of surgery after completion of neoadjuvant treatment

• Pathological Complete Response (pCR) Rate

  At the time of 1 month after resection

• Tumor Regression Grade (TRG)

  At the time of surgery after completion of neoadjuvant treatment

• Pathological Lymph Node Status (ypN0 Rate)

  At the time of surgery after completion of neoadjuvant treatment

Other Outcomes (4)

• Event-Free Survival (EFS)

  Up to 12 months after initiation of study treatment

• Overall Survival (OS)

  Up to 12 months after initiation of study treatment

• Disease-Free Survival (DFS)

  Up to 12 months after surgery

Study Arms (1)

Response-guided Sequential Treatment

EXPERIMENTAL

Participants will receive neoadjuvant chemoimmunotherapy followed by individualized treatment according to early tumor response assessment. Patients with favorable response will proceed to surgery, while patients with insufficient response but remaining resectable disease will receive sequential chemoradiotherapy followed by surgery.

Drug: Neoadjuvant Chemoimmunotherapy (Tislelizumab Plus Paclitaxel and Cisplatin); Radiation: Sequential Chemoradiotherapy

Interventions

Sequential Chemoradiotherapy RADIATION

Participants with inadequate response after neoadjuvant chemoimmunotherapy but remaining eligible for curative surgery will receive sequential chemoradiotherapy followed by surgery. Concurrent chemoradiotherapy consists of: Radiotherapy: 1.8 Gy per fraction, 5 fractions per week, for 5 weeks, with a total dose of 41.4 Gy in 23 fractions. Chemotherapy: weekly concurrent chemotherapy with paclitaxel and platinum-based chemotherapy during radiotherapy. The treatment aims to improve local tumor control before radical surgical resection.

Response-guided Sequential Treatment

Neoadjuvant Chemoimmunotherapy (Tislelizumab Plus Paclitaxel and Cisplatin) DRUG

Participants will receive neoadjuvant chemoimmunotherapy before surgery. The regimen includes: Tislelizumab (PD-1 inhibitor): 200 mg administered intravenously once every 3 weeks for 2 cycles. Paclitaxel: 135 mg/m² administered intravenously on Day 1 of each 3-week cycle for 2 cycles. Cisplatin: 60 mg/m² administered intravenously on Day 1 of each 3-week cycle for 2 cycles. After completion of neoadjuvant chemoimmunotherapy, tumor response will be assessed. Treatment decisions will be guided by early response evaluation and multidisciplinary surgical assessment.

Response-guided Sequential Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet all of the following criteria:
• Provide written informed consent before enrollment.
• Age \>18 years, male or female.
• Histologically confirmed thoracic esophageal squamous cell carcinoma (ESCC).
• Locally advanced, resectable disease according to AJCC/UICC 8th edition TNM staging system, defined as:
• cT3-4aN0-2M0 or cT1-2N1-2M0;
• No evidence of distant metastasis;
• Considered initially resectable by a multidisciplinary surgical team.
• Patients who have received neoadjuvant chemoimmunotherapy and have measurable disease response assessment according to RECIST v1.1, including complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD).
• At least one measurable lesion according to RECIST version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Expected survival time \>6 months.
• Adequate organ function meeting the following criteria:
• Bone marrow function:
• Absolute neutrophil count ≥1,500/mm³;

You may not qualify if:

• Participants will be excluded if any of the following criteria apply:
• Evidence of distant metastasis.
• Previous or concurrent malignancy, except adequately treated basal cell carcinoma of skin or cervical carcinoma in situ.
• Previous thoracic radiotherapy.
• Previous treatment with PD-1, PD-L1, or CTLA-4 inhibitors, or known hypersensitivity to PD-1 inhibitors or macromolecular protein products.
• Active autoimmune disease or history of clinically significant autoimmune disease requiring systemic treatment.
• Current use of immunosuppressive therapy or systemic corticosteroids exceeding the equivalent of prednisone 10 mg/day within 2 weeks before enrollment.
• Clinically significant ascites or pleural effusion requiring therapeutic drainage.
• Uncontrolled cardiovascular disease, including:
• NYHA class II or higher heart failure;
• Unstable angina;
• Myocardial infarction within 1 year;
• Clinically significant arrhythmias requiring treatment.
• Significant coagulation abnormalities, bleeding tendency, or ongoing thrombolytic/anticoagulant therapy.
• Active gastrointestinal disorders associated with bleeding or perforation risk, including esophageal varices, active gastric/duodenal ulcer, ulcerative colitis, portal hypertension, or active tumor bleeding.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Department of minimally invasive esophageal surgery, Tianjin Medical University Cancer Institute and Hospital

Tianjin, 300060, China

Location

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

tislelizumab; Paclitaxel; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Central Study Contacts

Hongjing Jiang, PhD,MD

CONTACT

18622221069; jianghongjing@tmu.edu.cn

Chunyu Hou, PhD

CONTACT

13652037579; houchunyu@tjmuch.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2026
• First Posted: July 22, 2026
• Study Start: July 14, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2031
• Last Updated: July 22, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)