Efficacy and Safety of Induction Chemo-Immunotherapy Followed by Radiotherapy vs Concurrent Chemoradiotherapy in Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Randomized, Two-Arm, Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 92
- 试验地点
- 1
- 主要终点
- Complete Response (CR) Rate at 3 Months After Radiotherapy (Investigator-Assessed)
研究概览
简要总结
This is a prospective, randomized, phase II clinical study in patients with unresectable stage III-IVA esophageal squamous cell carcinoma (ESCC). Eligible patients will be randomly assigned in a 1:1 ratio to two treatment groups. The experimental group will receive 3 cycles of induction therapy with PD-1 antibody plus chemotherapy, followed by radiotherapy, and then maintenance therapy with PD-1 antibody monotherapy. The control group will receive concurrent chemoradiotherapy, followed by maintenance therapy with PD-1 antibody monotherapy. The primary endpoints are the complete response (CR) rate at 3 months after radiotherapy (assessed by investigators) and the 1-year progression-free survival (PFS) rate. Secondary endpoints include overall survival (OS), progression-free survival (PFS), duration of response, objective response rate (ORR), local-regional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), quality of life, and safety profile.
详细描述
This is a prospective, randomized, two-arm, phase II clinical trial investigating induction chemo-immunotherapy followed by sequential radiotherapy versus concurrent chemo-immunotherapy plus radiotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC).
Current standard of care for unresectable locally advanced ESCC is definitive concurrent chemoradiotherapy. However, outcomes remain suboptimal, with high rates of local recurrence and distant metastasis. The addition of PD-1 inhibitors to concurrent chemoradiotherapy has shown promising activity in recent studies, but optimal sequencing and integration of immunotherapy with radiotherapy are still under investigation.
This trial is designed to evaluate whether an induction strategy with chemo-immunotherapy followed by radiotherapy can improve response rates and long-term survival compared to the standard concurrent approach. Patients will be randomized to receive either:
- Experimental arm: Three cycles of induction chemo-immunotherapy, followed by definitive thoracic radiotherapy, then maintenance immunotherapy for up to one year.
- Control arm: Concurrent chemo-immunotherapy plus definitive thoracic radiotherapy, followed by maintenance immunotherapy for up to one year.
The primary objective is to compare the efficacy of the two regimens in terms of complete response and progression-free survival. Safety, tolerability, and quality of life will also be assessed to support the risk-benefit profile of each strategy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed unresectable stage III-IVA esophageal squamous cell carcinoma (ESCC)
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Adequate organ function (bone marrow, liver, renal, cardiac) within 2 weeks prior to randomization
- •Measurable or evaluable disease per RECIST 1.1
- •Willing to provide written informed consent
排除标准
- •Previous radiotherapy to the chest or previous systemic chemotherapy for ESCC
- •History of other malignancies within the last 5 years (except cured basal cell carcinoma or cervical carcinoma in situ)
- •Severe comorbidities (uncontrolled hypertension, NYHA class III-IV heart failure, active infection, etc.)
- •Known hypersensitivity to any study drugs (paclitaxel, cisplatin/carboplatin, PD-1 antibody)
- •Pregnant or lactating women
- •Participation in another clinical trial within 30 days prior to randomization
研究组 & 干预措施
Experimental Group: Chemo-Immunotherapy Induction + Radiotherapy + PD-1 Maintenance
Patients receive 3 cycles of PD-1 antibody plus chemotherapy induction therapy, followed by thoracic radiotherapy (50.4Gy in 28 fractions), then PD-1 antibody maintenance therapy (200mg IV q3w, up to 1 year).
干预措施: Paclitaxel plus Cisplatin or Carboplatin (Induction Chemotherapy) (Drug)
Control Group: Concurrent Chemoradiotherapy + PD-1 Maintenance
Patients receive weekly paclitaxel + cisplatin/carboplatin concurrent with thoracic radiotherapy (50.4Gy in 28 fractions), then PD-1 antibody maintenance therapy (200mg IV q3w, up to 1 year).
干预措施: Weekly Paclitaxel plus Cisplatin or Carboplatin (Concurrent Chemotherapy) (Drug)
结局指标
主要结局
Complete Response (CR) Rate at 3 Months After Radiotherapy (Investigator-Assessed)
时间窗: 3 months after completion of radiotherapy
Proportion of patients achieving complete response (CR) per RECIST 1.1, assessed by investigators at 3 months after completion of radiotherapy
1-Year Progression-Free Survival (PFS) Rate
时间窗: 1 year after randomization
Proportion of patients alive and without disease progression at 1 year after randomization
次要结局
- Overall Survival (OS)(Up to 3 years after randomization)
- Progression-Free Survival (PFS)(Up to 3 years after randomization)
- Duration of Response (DOR)(Up to 3 years after randomization)
- Objective Response Rate (ORR)(Up to 3 years after randomization)
- Local Regional Failure-Free Survival (LRFS)(Up to 3 years after randomization)
- Distant Metastasis-Free Survival (DMFS)(Up to 3 years after randomization)
- Incidence of Treatment-Emergent Adverse Events (TEAEs)(From first study treatment to 30 days after last treatment)
- EORTC QLQ-OES18 Symptom Score Change(Baseline, 3 months, 6 months, 12 months after radiotherapy)
- EORTC QLQ-C30 Quality of Life Score Change(Baseline, 3 months, 6 months, 12 months after radiotherapy.)