NCT07272291尚未招募2 期
A Prospective, Single-Arm Phase II Study of Toripalimab Plus Chemotherapy and Low-Dose Radiotherapy as Neoadjuvant Treatment for Neoadjuvant Therapy-Refractory Esophageal Squamous Cell Carcinoma
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 48
- 主要终点
- Major Pathological Response (MPR) rate
研究概览
简要总结
The goal of this clinical trial is to evaluate the efficacy and safety of neoadjuvant toripalimab combined with chemotherapy and low-dose radiotherapy in patients with esophageal squamous cell carcinoma who are insensitive to neoadjuvant therapy. The main question it aims to answer is:
• Whether adding low dose radiotherapy can improve the efficacy of immunotherapy combined chemotherapy in neoadjuvant setting?
Participants will receive low-dose radiotherapy (1.2 Gy/fraction, 5 fractions), followed by 2 cycles of chemotherapy plus toripalimab (240 mg, q3w). 6 to 8 weeks after treatment completion, a systematic preoperative assessment is conducted, then surgery is performed. Postoperatively, management depends on pathological results:
Non-pathological complete response (non-pCR) patients: Toripalimab monotherapy continues until disease recurrence, intolerable toxicity, informed consent withdrawal, or for 1 year (whichever comes first).
Pathological complete response (pCR) patients: Directly undergo regular postoperative survival follow-up
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
- •Males and females aged ≥ 18 years;
- •Esophageal cancer staged as T1-4aN1-3M0 or T3-4aN0M0 (per AJCC 8th edition), with histologically confirmed predominant squamous cell carcinoma at initial diagnosis;
- •Subjects must complete 2 cycles of preoperative neoadjuvant immunotherapy combined with chemotherapy (any regimen) before enrollment, followed by imaging assessment showing stable disease (SD);
- •ECOG performance status score of 0 or 1;
- •All required baseline laboratory tests must be completed, with results obtained within 14 days before enrollment. Laboratory tests resluts must meet the following criteria (per CTCAE v5):
- •WBC ≥ 2000/μL Neutrophils ≥ 1500/μL Platelets ≥ 100 × 10³/μL Hemoglobin ≥ 9.0 g/dL Creatinine: Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance > 50 mL/min (per Cockcroft/Gault formula) AST ≤ 3 × ULN, ALT ≤ 3 × ULN Total bilirubin ≤ 1.5 × ULN (except subjects with Gilbert syndrome, for whom total bilirubin must be < 3 × ULN);
- •Tumor tissue and blood must be provided for biomarker analysis. If the provided tumor tissue is insufficient for analysis, additional archived tumor tissue (blocks and/or sections) must be obtained;
- •Subjects voluntarily participate in the study, sign a written informed consent form, and are compliant with follow-up;
- •Subjects must be willing and able to adhere to scheduled visits, treatment plans, laboratory tests, tumor biopsies, and other study requirements;
- •Females of childbearing potential must have a negative urine or serum pregnancy test within 7 days before enrollment, and agree to use effective contraception during the study and for at least 6 months after the last dose of toripalimab. Males with partners of childbearing potential must agree to use effective contraception during the study and for at least 6 months after the last dose.
排除标准
- •Subjects with a history of other malignant tumors are excluded, unless complete remission was achieved at least 5 years prior to study entry and no additional treatment is required or anticipated during the study period. Exceptions include, but are not limited to, basal or squamous cell carcinoma of the skin, superficial bladder cancer, or in situ carcinoma of the prostate, cervix, or breast.
- •Subjects with known or suspected active autoimmune diseases are excluded. However, enrollment is permitted for subjects with type 1 diabetes, hypothyroidism requiring only hormone replacement therapy, cutaneous conditions not requiring systemic treatment (e.g., vitiligo, psoriasis, or alopecia), or conditions not expected to recur in the absence of external triggers.
- •Subjects who required systemic treatment with corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive agents within 14 days prior to study drug administration are excluded. Inhaled or topical steroids, as well as adrenal replacement steroids, at doses exceeding 10 mg daily prednisone equivalent are allowed only in the absence of active autoimmune disease.
- •Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity are excluded.
- •All toxicities attributable to prior anticancer therapy (except nephropathy, neuropathy, hearing loss, alopecia, and fatigue) must resolve to Grade 1 (per NCI CTCAE Version 5) or baseline before study drug administration. Subjects with toxicities from prior anticancer therapy that are not expected to resolve and result in permanent sequelae (e.g., peripheral neuropathy following platinum-based therapy) are permitted, provided the peripheral neuropathy resolves to Grade 2 (per NCI CTCAE Version 5).
- •Subjects with any severe or uncontrolled medical condition or active infection that, in the investigator's judgment, may increase the risks of study participation or study drug administration, or impair the subject's ability to complete treatment per the protocol are excluded.
- •Subjects with a known positive human immunodeficiency virus (HIV) test result or a confirmed diagnosis of acquired immunodeficiency syndrome (AIDS) are excluded.
- •Subjects who received live/attenuated vaccines within 30 days prior to the first study treatment are excluded.
- •Subjects with active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are excluded, including those with: acute or chronic active hepatitis B/ C; HBV DNA >2000 IU/mL or 10⁴ copies/mL; HCV RNA >10³ copies/mL; or concurrent positivity for hepatitis B surface antigen (HBsAg) and anti-HCV antibodies.
- •Subjects with a history of allergy or hypersensitivity to any component of the study drug, or a history of severe hypersensitivity to any monoclonal antibody are excluded.
- •Subjects currently participating in other interventional clinical studies are excluded.
研究组 & 干预措施
Experimental Arm
Experimental
干预措施: Toripalimab (Drug)
结局指标
主要结局
Major Pathological Response (MPR) rate
时间窗: up to 12 months
MPR rate is defined as the proportion of participants who have achieved major pathological response（on routine hematoxylin and eosin staining, tumors with no more than 10% viable tumor cells) in all participants who have completed the neoadjuvant therapy and underwent surgery.
次要结局
- Overall Survival (OS)(up to 5 years)
- Pathological Complete Response (pCR) rate(up to 12 months)
- Event Free Survival (EFS)(up to 5 years)
研究者
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