Safety and Feasibility of Neoadjuvant Immunotherapy Combined With Chemotherapy Sequenced With Endoscopic Resection for Esophageal Cancer (Endosurgery-02)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Organ preservation rate
研究概览
简要总结
This single-center, prospective, single-arm study will evaluate whether giving neoadjuvant chemoimmunotherapy can safely shrink esophageal cancer and allow organ-preserving endoscopic removal in selected patients. Adults with esophageal cancer will receive at least two 3-week cycles of a PD-1 inhibitor (tislelizumab 200 mg on Day 1) plus carboplatin (AUC 3-5, Day 1) and nab-paclitaxel (≤260 mg/m², Day 1). During treatment, routine safety tests are performed. About 3-4 weeks after completing at least two cycles, participants undergo clinical reassessment with examinations and imaging (such as endoscopy, endoscopic ultrasound, PET/CT or CT of the neck, chest, and upper abdomen) to evaluate tumor shrinkage and possible spread. Tumor response is assessed using RECIST 1.1. If a clinical complete response is achieved without obvious nodal disease, endoscopic resection may be performed to preserve the esophagus; otherwise, patients may proceed to surgery or concurrent chemoradiation per clinical judgment. The study focuses on feasibility and safety of this organ-preserving approach and describes tumor responses after therapy. Potential benefits include tumor shrinkage and avoiding major surgery in selected cases; risks include side effects of standard chemotherapy/immunotherapy and procedure-related discomforts from biopsies or endoscopic treatments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cohort A - Potentially resectable ESCC:
- •Inclusion Criteria：
- •Age range: 18-80 years old;
- •Patients diagnosed with esophageal squamous cell carcinoma (ESCC) through histopathological examination of biopsy tissues from the primary tumor;
- •Patients with potentially resectable esophageal cancer confirmed by imaging and endoscopic examinations (T1b-3, N0, M0, with a tumor size not exceeding 5 cm and occupying less than 2/3 of the luminal circumference); Patients who have not received any antitumor treatment, including but not limited to surgery, radiotherapy, chemotherapy, immunotherapy, and targeted therapy;
- •Patients with a preoperative Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
- •Patients with a preoperative American Society of Anesthesiologists (ASA) physical status classification of I-III;
- •Female patients of reproductive age should have a negative pregnancy test and be willing to use effective contraceptive methods during the study period;
- •Patients who have signed the informed consent form.
排除标准
- •Patients with potential tracheoesophageal fistula or aortoesophageal fistula;
- •Patients with severe malnutrition or requiring tube feeding;
- •Patients with other malignancies that have not been cured within the past 2 years (except for cured basal cell carcinoma of the skin and cured carcinoma in situ of the cervix);
- •Patients with active autoimmune diseases or a history of autoimmune diseases or symptoms that require systemic corticosteroid treatment or anti-autoimmune drug therapy;
- •Immunocompromised patients, or patients who are still receiving systemic steroids (prednisone > 10 mg/day or equivalent) or other forms of immunosuppressive therapy within 7 days before the first dose of neoadjuvant therapy in this study;
- •Patients with active infections requiring systemic treatment within 7 days before the first neoadjuvant therapy in this study;
- •Patients with a history of allogeneic organ or stem cell transplantation;
- •Patients with allergies to drugs or related components involved in this study;
- •Patients who are currently participating in any other clinical study.
- •Cohort B - Surgery-contraindicated ESCC:
- •Inclusion Criteria:
- •Individuals aged above 18 years;
- •Patients diagnosed with esophageal squamous cell carcinoma through histopathological examination of biopsy tissues from the primary tumor;
- •Patients with esophageal cancer deemed as surgically contraindicated (including those with cervical esophageal cancer, surgical contraindications, those who refuse surgery, or those considered high-risk for esophagectomy, defined as having at least one of the following characteristics: (1) age over 75 years, (2) Charlson comorbidity index >= 2, (3) presence of moderate lung dysfunction, (4) malnutrition (with a body mass index below 18 kg/m^2)), with a clinical staging of cT1b-3N0M0, a tumor size not exceeding 5 cm, and occupying less than 2/3 of the luminal circumference;
- •Patients who have not undergone any antitumor treatment, including but not limited to surgery, radiotherapy, chemotherapy, immunotherapy, and targeted therapy;
- •Female patients of reproductive age should have a negative pregnancy test and be willing to adopt effective contraceptive measures during the study period;
- •Patients who have signed the informed consent form.
- •Exclusion Criteria:
- •Patients with allergies to the drugs or related components involved in this study;
- •Patients who are currently participating in any other clinical study.
研究组 & 干预措施
Neoadjuvant Tislelizumab + Carboplatin + Nab-Paclitaxel
Participants receive neoadjuvant chemoimmunotherapy for at least two 3-week cycles: tislelizumab 200 mg IV on Day 1 (Q3W) plus carboplatin AUC 3-5 IV on Day 1 (Q3W) and nab-paclitaxel ≤260 mg/m² IV on Day 1 (Q3W; ~30-minute infusion). Safety is assessed during treatment. About 3-4 weeks after completing ≥2 cycles, participants undergo clinical reassessment (physical exam, labs, and imaging including endoscopy/EUS and PET/CT or CT of neck, chest, and upper abdomen) and tumor response is evaluated by RECIST 1.1. If clinical complete response (cCR) is achieved without obvious nodal disease, endoscopic resection is performed 3-6 weeks after neoadjuvant therapy; otherwise, patients proceed to standard esophagectomy or concurrent chemoradiation per investigator judgment.
干预措施: Tislelizumab (Drug)
Neoadjuvant Tislelizumab + Carboplatin + Nab-Paclitaxel
Participants receive neoadjuvant chemoimmunotherapy for at least two 3-week cycles: tislelizumab 200 mg IV on Day 1 (Q3W) plus carboplatin AUC 3-5 IV on Day 1 (Q3W) and nab-paclitaxel ≤260 mg/m² IV on Day 1 (Q3W; ~30-minute infusion). Safety is assessed during treatment. About 3-4 weeks after completing ≥2 cycles, participants undergo clinical reassessment (physical exam, labs, and imaging including endoscopy/EUS and PET/CT or CT of neck, chest, and upper abdomen) and tumor response is evaluated by RECIST 1.1. If clinical complete response (cCR) is achieved without obvious nodal disease, endoscopic resection is performed 3-6 weeks after neoadjuvant therapy; otherwise, patients proceed to standard esophagectomy or concurrent chemoradiation per investigator judgment.
干预措施: Carboplatin (Drug)
Neoadjuvant Tislelizumab + Carboplatin + Nab-Paclitaxel
Participants receive neoadjuvant chemoimmunotherapy for at least two 3-week cycles: tislelizumab 200 mg IV on Day 1 (Q3W) plus carboplatin AUC 3-5 IV on Day 1 (Q3W) and nab-paclitaxel ≤260 mg/m² IV on Day 1 (Q3W; ~30-minute infusion). Safety is assessed during treatment. About 3-4 weeks after completing ≥2 cycles, participants undergo clinical reassessment (physical exam, labs, and imaging including endoscopy/EUS and PET/CT or CT of neck, chest, and upper abdomen) and tumor response is evaluated by RECIST 1.1. If clinical complete response (cCR) is achieved without obvious nodal disease, endoscopic resection is performed 3-6 weeks after neoadjuvant therapy; otherwise, patients proceed to standard esophagectomy or concurrent chemoradiation per investigator judgment.
干预措施: Nab-paclitaxel (Drug)
Neoadjuvant Tislelizumab + Carboplatin + Nab-Paclitaxel
Participants receive neoadjuvant chemoimmunotherapy for at least two 3-week cycles: tislelizumab 200 mg IV on Day 1 (Q3W) plus carboplatin AUC 3-5 IV on Day 1 (Q3W) and nab-paclitaxel ≤260 mg/m² IV on Day 1 (Q3W; ~30-minute infusion). Safety is assessed during treatment. About 3-4 weeks after completing ≥2 cycles, participants undergo clinical reassessment (physical exam, labs, and imaging including endoscopy/EUS and PET/CT or CT of neck, chest, and upper abdomen) and tumor response is evaluated by RECIST 1.1. If clinical complete response (cCR) is achieved without obvious nodal disease, endoscopic resection is performed 3-6 weeks after neoadjuvant therapy; otherwise, patients proceed to standard esophagectomy or concurrent chemoradiation per investigator judgment.
干预措施: Endoscopic resection (Procedure)
Neoadjuvant Tislelizumab + Carboplatin + Nab-Paclitaxel
Participants receive neoadjuvant chemoimmunotherapy for at least two 3-week cycles: tislelizumab 200 mg IV on Day 1 (Q3W) plus carboplatin AUC 3-5 IV on Day 1 (Q3W) and nab-paclitaxel ≤260 mg/m² IV on Day 1 (Q3W; ~30-minute infusion). Safety is assessed during treatment. About 3-4 weeks after completing ≥2 cycles, participants undergo clinical reassessment (physical exam, labs, and imaging including endoscopy/EUS and PET/CT or CT of neck, chest, and upper abdomen) and tumor response is evaluated by RECIST 1.1. If clinical complete response (cCR) is achieved without obvious nodal disease, endoscopic resection is performed 3-6 weeks after neoadjuvant therapy; otherwise, patients proceed to standard esophagectomy or concurrent chemoradiation per investigator judgment.
干预措施: Esophagectomy (Procedure)
Neoadjuvant Tislelizumab + Carboplatin + Nab-Paclitaxel
Participants receive neoadjuvant chemoimmunotherapy for at least two 3-week cycles: tislelizumab 200 mg IV on Day 1 (Q3W) plus carboplatin AUC 3-5 IV on Day 1 (Q3W) and nab-paclitaxel ≤260 mg/m² IV on Day 1 (Q3W; ~30-minute infusion). Safety is assessed during treatment. About 3-4 weeks after completing ≥2 cycles, participants undergo clinical reassessment (physical exam, labs, and imaging including endoscopy/EUS and PET/CT or CT of neck, chest, and upper abdomen) and tumor response is evaluated by RECIST 1.1. If clinical complete response (cCR) is achieved without obvious nodal disease, endoscopic resection is performed 3-6 weeks after neoadjuvant therapy; otherwise, patients proceed to standard esophagectomy or concurrent chemoradiation per investigator judgment.
干预措施: Concurrent chemoradiation (Radiation)
结局指标
主要结局
Organ preservation rate
时间窗: Up to 12 months after completion of neoadjuvant therapy
Proportion of enrolled participants who achieve esophageal organ preservation after neoadjuvant therapy, defined as: (1) clinical complete response at reassessment \~3-4 weeks after ≥2 cycles; (2) endoscopic tumor resection (e.g., ESD) performed 3-6 weeks after therapy with curative intent and negative margins (R0) when resection is undertaken; and (3) no planned or salvage esophagectomy through 12 months. Participants who require esophagectomy, have persistent/progressive disease precluding endoscopic therapy, or die before assessment are counted as non-preserved.
Overall safety: incidence of Grade ≥3 adverse events related to drug, endoscopic procedures, surgery, or radiation
时间窗: Adverse event was assessed peri-procedural of drug-using, endoscopic procedures, surgery, or radiation up to 30 days
Proportion of participants with at least one Grade ≥3 adverse event from any study-specified modality: 1. Drug-related treatment-related adverse events (TRAEs) graded by CTCAE v5.0 . 2. Endoscopic complications when resection is performed (clinically significant bleeding requiring intervention, perforation, or stricture requiring dilation/stenting), adjudicated per institutional/ASGE criteria; 3. Surgical morbidity after esophagectomy (Clavien-Dindo grade ≥III within 90 days of surgery); 4. Radiation toxicities among those receiving concurrent chemoradiation (CTCAE v5.0 grade ≥3). Serious adverse events (SAEs) (death, life-threatening event, inpatient hospitalization/prolongation, disability, or other medically important event) and 30-/90-day all-cause mortality are captured; if multiple events occur, the worst grade counts for this composite endpoint
Two-year overall survival rate
时间窗: From Day 1 of the first neoadjuvant dose to 24 months
Proportion of participants alive 24 months after index date regardless of cause of death (all-cause mortality). The index date is Day 1 of the first neoadjuvant cycle. Survival status is ascertained from clinic visits, hospital records, and scheduled follow-up contacts. The OS rate at 24 months will be estimated using the Kaplan-Meier method with 95% confidence interval. Participants alive at last contact before 24 months are censored at that date; deaths at any time up to 24 months count as events, including those occurring after endoscopic resection, esophagectomy, or chemoradiation.
Biomarkers
时间窗: Baseline and the day 1 of endoscopy or surgery
Tumor tissue samples and blood samples will be collected for tumor biomarker analysis, including but not limited to analyses of metabolic markers, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), T-cell receptor sequencing (TCR-seq), and RNA sequencing (RNA-seq).
次要结局
未报告次要终点