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
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 354
- 试验地点
- 1
- 主要终点
- progression free survival (PFS）
研究概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
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
- •An eastern cooperative oncology group (ECOG) score of 0-
- •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.
排除标准
- •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.
研究组 & 干预措施
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).
干预措施: Two arms adopt local intervention administered at distinct timings. (Other)
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).
干预措施: Two arms adopt local intervention administered at distinct timings. (Other)
结局指标
主要结局
progression free survival (PFS）
时间窗: 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.
overall survival (OS)
时间窗: 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.
次要结局
未报告次要终点
研究者
Kuai Le Zhao, MD
Chief physician
Fudan University