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Updated May 2026 · ClinicalTrials.gov

RECRUITINGPhase 2INTERVENTIONAL

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

Comparison of Neoadjuvant Chemoradiotherapy Followed by Immunotherapy With Neoadjuvant Chemoimmunotherapy in the Treatment for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Multi-center, Phase II Randomized Clinical Study

Neoadjuvant ChemoRadiotherapy Followed by Immunotherapy and Surgery for Resectable Esophageal Squamous Cell Carcinoma(CRIS-2 Trial) (NCT06509568) is a Phase 2 interventional studying Esophageal Squamous Cell Carcinoma, sponsored by Zhejiang Cancer Hospital. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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 patients will be randomly assigned in a 1:1 ratio to either the nCRIT group or the nCIT group. Patients in the nCRIT group will receive neoadjuvant concurrent chemoradiotherapy: radiation therapy will be administered using IMRT or VMAT with involved-field irradiation at a dose of PTV 41.4 Gy/23 fractions/31 days. Chemotherapy will consist of weekly administration of paclitaxel (albumin-bound) 50 mg/m² and carboplatin (AUC=2) for five weeks, given on the days of radiotherapy. Patients who do not progress on CT and meet immunotherapy criteria will receive fixed-dose tislelizumab (200 mg IV) on days 8 and 29 after chemoradiotherapy, followed by minimally invasive esophagectomy four weeks after completing immunotherapy. Patients in the nCIT group will receive two cycles of TC chemotherapy combined with immunotherapy, specifically paclitaxel (albumin-bound) 100 mg/m² on days 1, 8, 15 or 260mg/m² d1, carboplatin (AUC=5) on days 1, and tislelizumab (200 mg) on days 1. Minimally invasive esophagectomy will be performed 4-6 weeks after completing chemotherapy, and adjuvant immunotherapy is recommended for one year after surgery. The primary endpoint of the study is the pathological complete response (pCR). Secondary endpoints include treatment safety, CT imaging response rate, R0 resection rate, major pathological response (MPR), 2-year event-free survival (EFS), 2-year overall survival (OS) in the intention-to-treat (ITT) population, and analysis of treatment failure reasons.

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Esophageal Squamous Cell Carcinoma and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 92 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Esophageal Squamous Cell Carcinoma subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: 1. Age and Consent: Subjects must be male or female, aged ≥18 and ≤75 years at the time of signing the willing to sign a consent form 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: diagnosed by tissue sample (biopsy-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. blood count (hemoglobin) at least 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. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
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 abuse. 23. Local or systemic diseases caused by non-malignant tumors; or diseases or symptoms secondary to tumors that may lead to high medical risk and/or uncertainty in survival assessment, such as tumor leukemoid reaction (white blood cell count \> 20×10\^9/L), cachexia (e.g., known weight loss of more than 10% in the 3 months prior to screening). 24. Any condition that the investigator believes may pose a risk to the subject's participation in the study, interfere with the evaluation of the study drug, or affect the interpretation of study results.

Treatments Being Tested

RADIATION

Neoadjuvant chemoradiotherapy followed by immunotherapy

Patients in the nCRIT group will receive neoadjuvant concurrent chemoradiotherapy: radiation therapy will be administered using IMRT or VMAT with involved-field irradiation at a dose of PTV 41.4 Gy/23 fractions/31 days. Chemotherapy will consist of weekly administration of paclitaxel (albumin-bound) 50 mg/m² and carboplatin (AUC 2) for five weeks, given on the days of radiotherapy. Patients who do not progress on CT and meet immunotherapy criteria will receive fixed-dose tislelizumab (200 mg IV) on days 8 and 29 after chemoradiotherapy, followed by minimally invasive esophagectomy four weeks after completing immunotherapy.

DRUG

Neoadjuvant chemoimmunotherapy

Patients in the nCIT group will receive two cycles of TC chemotherapy combined with immunotherapy, specifically paclitaxel (albumin-bound) 100 mg/m² on days 1, 8, 15 or 260mg/m² d1, carboplatin (AUC=5) on days 1, and tislelizumab (200 mg) on days 1. Minimally invasive esophagectomy will be performed 4-6 weeks after completing chemotherapy, and adjuvant immunotherapy is recommended for one year after surgery.

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Zhejiang Cancer Hospital
Hangzhou, Zhejiang, China

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06509568), the sponsor (Zhejiang Cancer Hospital), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06509568 clinical trial studying?

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 p… The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT06509568?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06509568?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06509568. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06509568. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.