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Neoadjuvant ChemoRadiotherapy Followed by Immunotherapy and Surgery for Resectable Esophageal Squamous Cell Carcinoma(CRIS-2 Trial)

RecruitingPhase 2Ages 18 Years - 75 YearsAllZhejiang Cancer Hospital
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In plain words

What the trial is, and whether it could suit you

Based on our previous single-arm Phase Ib study (CRIS trial, NCT06303583), we observed that neoadjuvant chemoradiotherapy followed by immunotherapy (nCRIT) significantly increased the pathological complete response (pCR) rate, achieving approximately 60% in locally advanced esophageal squamous cell carcinoma(ESCC). We plan to initiate a multicenter, prospective, randomized phase II trial designed to compare the efficacy and safety of neoadjuvant chemoimmunotherapy (nCIT) versus neoadjuvant chemoradiotherapy followed by immunotherapy (nCRIT) in treating esophageal squamous cell carcinoma. The primary study population includes patients with operable or potentially operable thoracic ESCC classified as cT3-4aN0 or T2-4aN+ based on endoscopy, enhanced chest and abdominal CT, and whole-body PET scans. Eligible participants are aged 18-75 years with an ECOG performance status of 0-1. Qualified

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📋 Eligibility rules (as published)
Inclusion Criteria: 1. Age and Consent: Subjects must be male or female, aged ≥18 and ≤75 years at the time of signing the informed consent form. 2. Performance Status: Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1, or a Karnofsky Performance Status (KPS) score of ≥80. 3. Histological Confirmation: Histologically confirmed thoracic esophageal squamous cell carcinoma (ESCC), with the upper boundary of the lesion not exceeding the thoracic inlet. 4. Resectability: Subjects must have resectable or potentially resectable T3-4aN0 or T2-4aN+ ESCC, as per the AJCC/UICC 8th edition clinical staging (cTNM). 5. Lesion Length: The length of the esophageal lesion must be \<8 cm. 6. Surgical Eligibility: Subjects must have no contraindications for surgical procedures. 7. Organ Function: Subjects must have good cardiopulmonary function and other organ functions to tolerate chemoradiotherapy and surgery. a. Hematology (without the use of any blood components and cell growth factor support treatment within 7 days before the start of study treatment): i. Absolute neutrophil count (ANC) ≥ 1.5×10\^9/L (1500/mm\^3). ii. Platelet count ≥ 100×10\^9/L (100000/mm\^3). iii. Hemoglobin ≥ 90 g/L. b. Renal Function: i. Calculated creatinine clearance\* (CrCl) ≥ 50 mL/min. \*CrCl will be calculated using the Cockcroft-Gault formula: CrCl (mL/min) = (140 - age) × weight (kg) × F / (SCr (mg/dL) × 72), where F = 1 for males and 0.85 for females; SCr = serum creatinine. ii. Urine protein \< 2+ or 24-hour urine protein quantification \< 1.0 g. c. Liver Function: i. Serum total bilirubin (TBiL) ≤ 1.5 × ULN (Upper Limit of Normal). ii. AST and ALT ≤ 2.5 × ULN; for subjects with liver metastasis, AST and ALT ≤ 5 × ULN. iii. Serum albumin (ALB) ≥ 28 g/L. d. Coagulation Function: International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (unless the subject is receiving anticoagulant therapy and INR and APTT are within the expected therapeutic range). e. Cardiac Function: Left ventricular ejection fraction (LVEF) ≥ 60%. 8. Female Subjects of Childbearing Potential: Must have a negative urine or serum pregnancy test within 3 days prior to the first dose (if the urine pregnancy test is inconclusive, a serum pregnancy test will be required, and the serum result will be definitive). If a female subject of childbearing potential engages in sexual activity with an unsterilized male partner, she must use highly effective contraception from the start of screening and agree to continue using it for 120 days after the last dose of the study drug. Decisions regarding contraception discontinuation after this period should be discussed with the investigator. 9. Male Subjects with Female Partners of Childbearing Potential: Must use effective contraception from the start of screening until 120 days after the last dose of the study drug. Decisions regarding contraception discontinuation after this period should be discussed with the investigator. 10. Compliance: Subjects must be adequately informed and sign the informed consent form. They must also be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study requirements. Exclusion Criteria: 1. Cervical esophageal cancer (lesion located in the cervical esophagus). 2. Metastasis to cervical lymph nodes or lymph nodes around the celiac artery. 3. Invasion of the trachea or aorta. 4. Hoarseness caused by the esophageal tumor. 5. Esophageal fistula or a tendency to develop an esophageal fistula. 6. Pregnant or lactating patients. 7. Severe, poorly controlled diabetes mellitus. 8. Inability to use the stomach for esophageal replacement due to previous surgeries. 9. Previous receipt of chemoradiotherapy. 10. Allergy or contraindication to taxane drugs. 11. Inability to provide informed consent due to psychological, familial, or social reasons. 12. History of malignancies other than esophageal cancer. 13. Inability to tolerate chemoradiotherapy due to severe cardiac, pulmonary, hepatic, renal dysfunction, hematologic diseases, or cachexia; BMI \< 18.5. 14. Active autoimmune disease, history of autoimmune disease (including but not limited to colitis, hepatitis, hyperthyroidism, etc.), history of immune deficiency (including positive HIV test), or other congenital or acquired immune deficiency disorders, organ transplantation, or allogeneic bone marrow transplantation. 15. Active hepatitis B (HBV DNA ≥ 2000 IU/mL or 10\^4 copies/mL), active hepatitis C (positive hepatitis C antibody with HCV-RNA levels above the detection limit). 16. History of immunodeficiency; positive HIV antibody test; currently on long-term systemic corticosteroids or other immunosuppressants. 17. Severe infections within 4 weeks prior to the first dose, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia; active infections requiring systemic anti-infective therapy within 2 weeks before the first dose (excluding antiviral treatment for hepatitis B or C). 18. Known active tuberculosis (TB); suspected active TB should be ruled out by clinical examination; known active syphilis infection. 19. Receipt of live or attenuated live vaccines within 30 days prior to the first dose or planned receipt of such vaccines during the study period (inactivated vaccines are allowed). 20. History of interstitial lung disease or non-infectious pneumonitis. 21. History of myocarditis, cardiomyopathy, malignant arrhythmias; unstable angina requiring hospitalization, myocardial infarction, congestive heart failure (NYHA class 2 or above), or vascular disease (e.g., aneurysms at risk of rupture) within 12 months prior to the first dose; or other cardiac conditions that may affect the safety evaluation of the study drug (e.g., poorly controlled arrhythmias, myocardial ischemia). 22. Known psychiatric disorders, drug abuse, alcoholism, or a history of substance
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What it tests

  • Neoadjuvant chemoradiotherapy followed by immunotherapy
  • Neoadjuvant chemoimmunotherapy
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Where

1 site
Zhejiang Cancer Hospital
Hangzhou, China
🤝 Taking part is your choice, and you can leave at any time. Only the trial team can confirm you are eligible — always decide together with your own doctor.
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