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Esophageal Squamous Cell CarcinomaPhase 2NCT06509568

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

A Phase 2 study testing Neoadjuvant chemoradiotherapy followed by immunotherapy and Neoadjuvant chemoimmunotherapy in people with Esophageal Squamous Cell Carcinoma, run by Zhejiang Cancer Hospital at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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). Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Esophageal Squamous Cell Carcinoma
What is being tested?
Neoadjuvant chemoradiotherapy followed by immunotherapy and Neoadjuvant chemoimmunotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
92 participants
Where
1 siteChina
Study dates
1 Aug 2024to 1 Aug 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age and Consent: Subjects must be male or female, aged ≥18 and ≤75 years at the time of signing the informed consent form.
  • 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.
  • Histological Confirmation: Histologically confirmed thoracic esophageal squamous cell carcinoma (ESCC), with the upper boundary of the lesion not exceeding the thoracic inlet.
  • Resectability: Subjects must have resectable or potentially resectable T3-4aN0 or T2-4aN+ ESCC, as per the AJCC/UICC 8th edition clinical staging (cTNM).
  • Lesion Length: The length of the esophageal lesion must be <8 cm.
  • Surgical Eligibility: Subjects must have no contraindications for surgical procedures.
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  • Organ Function: Subjects must have good cardiopulmonary function and other organ functions to tolerate chemoradiotherapy and surgery.
  • 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.
  • 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).
  • Cardiac Function: Left ventricular ejection fraction (LVEF) ≥ 60%.
  • 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.
  • 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.
  • 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.

Who cannot join

  • Cervical esophageal cancer (lesion located in the cervical esophagus).
  • Metastasis to cervical lymph nodes or lymph nodes around the celiac artery.
  • Invasion of the trachea or aorta.
  • Hoarseness caused by the esophageal tumor.
  • Esophageal fistula or a tendency to develop an esophageal fistula.
  • Pregnant or lactating patients.
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  • Severe, poorly controlled diabetes mellitus.
  • Inability to use the stomach for esophageal replacement due to previous surgeries.
  • Previous receipt of chemoradiotherapy.
  • Allergy or contraindication to taxane drugs.
  • Inability to provide informed consent due to psychological, familial, or social reasons.
  • History of malignancies other than esophageal cancer.
  • Inability to tolerate chemoradiotherapy due to severe cardiac, pulmonary, hepatic, renal dysfunction, hematologic diseases, or cachexia; BMI < 18.5.
  • 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.
  • 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).
  • History of immunodeficiency; positive HIV antibody test; currently on long-term systemic corticosteroids or other immunosuppressants.
  • 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).
  • Known active tuberculosis (TB); suspected active TB should be ruled out by clinical examination; known active syphilis infection.
  • 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).
  • History of interstitial lung disease or non-infectious pneumonitis.
  • 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).
  • Known psychiatric disorders, drug abuse, alcoholism, or a history of substance abuse.
  • 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).
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Yang Yang contact

057188128182

yangyang@zjcc.org.cn

Weizhen Xu contact

xuwz@zjcc.org.cn

China1 site, 1 recruiting

  • Zhejiang Cancer Hospital

    Hangzhou, Zhejiang

    YANG YANG, M.D., +8657188128182, yangyang@zjcc.org.cn

    Youhua Jiang

    Recruiting

Other trials in China

About this study

Official title: 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

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.

Read more

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.

Being tested
Neoadjuvant chemoradiotherapy followed by immunotherapy, Neoadjuvant chemoimmunotherapy
Medical subject headings
Esophageal Squamous Cell Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Neoadjuvant chemoradiotherapy followed by immunotherapyRadiation

    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.

  • Neoadjuvant chemoimmunotherapyDrug

    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.

Study groups in NCT06509568
Study groupRoleWhat they receive
Neoadjuvant chemoradiotherapy followed by immunotherapy (nCRIT)ExperimentalPatients 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.
Receives: Radiation: Neoadjuvant chemoradiotherapy followed by immunotherapy
Neoadjuvant chemoimmunotherapy (nCIT)Active comparatorPatients 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.
Receives: Drug: Neoadjuvant chemoimmunotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. pCR

    Pathologic complete response (pCR) was defined as the absence of cancer cells in both the esophagus and lymph nodes following neoadjuvant chemoradiotherapy

    Measured: 1 months after surgery

Secondary outcomes (6)

  1. R0 resection rate

    R0 resection rate refers to the proportion of patients who undergo a surgical procedure to remove a tumor and achieve a complete resection with no residual microscopic disease.

    Measured: 1 months after surgery

  2. MPR

    Major pathological response (MPR) is a measure of neoadjuvant immunotherapy efficacy. It is defined as having no more than 10% residual viable tumor cells by routine hematoxylin and eosin (H\&E) staining after therapy.

    Measured: 1 months after surgery

  3. 2-year EFS

    Event-Free Survival (EFS) refers to the length of time after the treatment starts during which a patient remains free from certain negative events, such as disease progression, recurrence, or death from any cause.

    Measured: 2 years after randomization

  4. 2-year OS

    Time from randomization to any death

    Measured: 2 years after randomization

  5. Adverse Events

    any undesirable experiences or side effects that occur in a patient during the trial

    Measured: 2 years after randomization

  6. HRQoL

    Health-Related Quality of Life (HRQoL) refers to a patient's overall well-being, encompassing physical, mental, and social aspects of health as they are affected by a medical condition or its treatment.

    Measured: 2 years after randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jul 2024
  2. Study start1 Aug 2024
  3. Primary completion1 Aug 2026 (estimated)
  4. Study completion1 Aug 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
92 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06509568
Sponsor's protocol ID
IIT-2024-238
Status last verified
Aug 2025
First submitted
12 Jul 2024
Last updated
29 Aug 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, van der Gaast A; CROSS Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012 May 31;366(22):2074-84. doi: 10.1056/NEJMoa1112088.

    PubMed 22646630

  • Luo H, Lu J, Bai Y, Mao T, Wang J, Fan Q, Zhang Y, Zhao K, Chen Z, Gao S, Li J, Fu Z, Gu K, Liu Z, Wu L, Zhang X, Feng J, Niu Z, Ba Y, Zhang H, Liu Y, Zhang L, Min X, Huang J, Cheng Y, Wang D, Shen Y, Yang Q, Zou J, Xu RH; ESCORT-1st Investigators. Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma: The ESCORT-1st Randomized Clinical Trial. JAMA. 2021 Sep 14;326(10):916-925. doi: 10.1001/jama.2021.12836.

    PubMed 34519801

  • Qin J, Xue L, Hao A, Guo X, Jiang T, Ni Y, Liu S, Chen Y, Jiang H, Zhang C, Kang M, Lin J, Li H, Li C, Tian H, Li L, Fu J, Zhang Y, Ma J, Wang X, Fu M, Yang H, Yang Z, Han Y, Chen L, Tan L, Dai T, Liao Y, Zhang W, Li B, Chen Q, Guo S, Qi Y, Wei L, Li Z, Tian Z, Kang X, Zhang R, Li Y, Wang Z, Chen X, Hou Z, Zheng R, Zhu W, He J, Li Y. Neoadjuvant chemotherapy with or without camrelizumab in resectable esophageal squamous cell carcinoma: the randomized phase 3 ESCORT-NEO/NCCES01 trial. Nat Med. 2024 Sep;30(9):2549-2557. doi: 10.1038/s41591-024-03064-w. Epub 2024 Jul 2.

    PubMed 38956195

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Neoadjuvant chemoradiotherapy followed by immunotherapy and Neoadjuvant chemoimmunotherapy in people with Esophageal Squamous Cell Carcinoma, run by Zhejiang Cancer Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 29 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Yang Yang (057188128182, yangyang@zjcc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

pCR (time frame: 1 months after surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06509568, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2025.

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