PD-1 Inhibitors Combined With Local Therapy at Different Timings in Oligometastatic ESCC (ESO-shanghai31)
A Phase III Randomized Controlled Study Investigating the Combination of PD-1 Inhibitors With Local Therapy Administered at Distinct Treatment Timings Among Patients With Oligometastatic Esophageal Squamous Cell Carcinoma
Although immunotherapy combined with chemotherapy has become the first-line standard regimen for advanced esophageal squamous cell carcinoma (ESCC) and improved clinical outcomes in advanced patients, the prognosis of patients with esophageal cancer remains unsatisfactory, with a 5-year overall survival rate below 20%. As an effective modality for local disease control, local radiotherapy has no established optimal sequencing schedule when combined with systemic therapy. The timing of radiotherapy intervention may directly affect treatment efficacy, treatment tolerance and quality of life of patients.
Several studies have explored the impact of radiotherapy timing in oligometastatic ESCC, yet substantial limitations persist in current evidence, resulting in a lack of unified guideline recommendations and wide heterogeneity in clinical practice. Most existing investigations are retrospective or small-sample prospective studies with high heterogeneity in study design, patient population selection and treatment regimens, yielding inconsistent conclusions that cannot support consistent clinical consensus.
To clarify the impact of radiotherapy timing on clinical efficacy in oligometastatic esophageal cancer, the investigator designed the present clinical trial. This study aims to compare the efficacy and safety of concurrent radiotherapy versus sequential radiotherapy on the basis of immunochemotherapy among patients with oligometastatic ESCC, so as to fill the evidence gap in existing research.
研究概览
地位
研究类型
注册 (估计的)
联系人和位置
学习联系方式
- 姓名:Guangmin Mao
- 电话号码:86-13732284526
- 邮箱:melly01@256.com
研究联系人备份
- 姓名:Kuaile Zhao
- 电话号码:86-18017312534
- 邮箱:kuaile_z@fudan.edu.cn
学习地点
-
-
Shanghai Municipality
-
Shanghai、Shanghai Municipality、中国
- 招聘中
- Fudan University Shanghai Cancer Center
-
接触:
- Guangmin Mao
- 电话号码:86-13732284526
- 邮箱:melly01@126.com
-
首席研究员:
- Kuaile Zhao, MD
-
-
参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
取样方法
研究人群
描述
Inclusion Criteria:
- An eastern cooperative oncology group (ECOG) score of 0-1.
- Histologically or cytologically confirmed diagnosis of esophageal squamous cell carcinoma.
- Genuine oligometastasis (without a history of polyme-tastatic disease).
- A total of four or fewer distant metastases, a maximum of three metastases in a single organ, and a maximum diameter of each metastatic lesion not exceeding 5 cm.
- Biopsy of a metastatic lesion, PET/CT scan, and PD-L1 CPS (IHC 22C3) are not required but preferred.
- No history of anti-PD-1/PD-L1 therapy. However, the following conditions are also eligible for inclusion: the use of anti-PD1/PD-L1 during induction/neoadjuvant/ concurrent therapy, or the use of anti-PD1/PD-L1 for maintenance therapy but not due to toxicity or disease progression interrupting anti-PD1/PD-L1 treatment, and the interruption has lasted for more than 3 months.
- Adequate hematological, hepatic, renal, and coagula-tion function. Baseline laboratory tests required to assess eligibility, including ANC ≥ 1.5 × 10^9/L, PLT ≥ 80 × 10^9/L, Hb ≥85 g/L, ALB ≥28 g/L, TBIL ≤ 1.5 × ULN, ALT and AST ≤ 3 × ULN, Cr ≤ 1.5 × ULN or CrCl ≥40 mL/min, FEV1 ≥ 1 L. (liver metastases ALT and AST ≤ 5 × ULN, liver or bone metastases AKP ≤ 5 × ULN).(9) Enrolled voluntarily and signed informed consent by the patient himself or his legal representative.
Exclusion Criteria:
- Pregnant or lactating women.
- Lung V20 remains over 25%.
- Confirmed diagnosis or clinical suspicion of esophageal fistula.
- Recurrence in the irradiated field.
- Active infection requiring systemic therapy.
- Active autoimmune disease requiring systemic treat-ment in the past 2 years.
- Immunodeficiency diagnosis, systemic steroid therapy, or any immunosuppressive treatment within 7 days before the first study treatment dose.
- Patients with a known history of grade 3 or higher adverse events, which are unsuitable for Anti-PD-1 therapy or adverse events that have not recovered to ≤CTCAE grade 1 (except alopecia).
- Uncontrolled pleural effusion, pericardial effusion, or pelvic ascites requiring repeated drainage.
Unable or rejection to receive Anti-PD-1 therapy or unable to comply with study requirements or follow-up schedule.(11) Inability to provide informed consent.
-
学习计划
研究是如何设计的?
设计细节
队列和干预
团体/队列 |
干预/治疗 |
|---|---|
|
Early Local Therapy Arm
Patients assigned to this study arm will initiate local therapy prior to the administration of the first two cycles of systemic treatment (immunotherapy or chemoimmunotherapy).
|
Both study arms receive chemoimmunotherapy combined with local intervention modalities, which encompass radiotherapy, surgery and ablation.
In the early local therapy arm, local intervention is initiated within 2 cycles of chemoimmunotherapy, whereas patients in the delayed local therapy arm start local intervention after completing 4 cycles of chemoimmunotherapy.
|
|
Delayed Local Therapy Arm
Patients assigned to this study arm will initiate local therapy after completion of the first four cycles of systemic treatment (immunotherapy or chemoimmunotherapy).
|
Both study arms receive chemoimmunotherapy combined with local intervention modalities, which encompass radiotherapy, surgery and ablation.
In the early local therapy arm, local intervention is initiated within 2 cycles of chemoimmunotherapy, whereas patients in the delayed local therapy arm start local intervention after completing 4 cycles of chemoimmunotherapy.
|
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
progression free survival (PFS)
大体时间:3-years
|
PFS is defined as the time interval between the date of the first treatment and the date of first confirmed disease progression or death from any cause.
If the patient does not have tumor progression or death at the time of data analysis, the time of the last tumor evaluation will be used as the endpoint for PFS.
|
3-years
|
|
overall survival (OS)
大体时间:3-years
|
the interval between the date of first systemic treatment and the date of death from any cause, and for patients who are still alive at the time point of the final analysis, the time of their last contact will be used as the survival time.
|
3-years
|
合作者和调查者
调查人员
- 研究主任:Kuaile Zhao, MD、Fudan University
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.