Hypofractionated vs. Conventional Chemoradiotherapy After Induction Chemo-immunotherapy for Unresectable Esophageal Squamous Cell Carcinoma

Comparing Hypofractionated Concurrent Chemoradiotherapy Versus Conventional Fractionated Concurrent Chemoradiotherapy Following Induction Chemo-immunotherapy in Patients With Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Prospective, Open-Label, Randomized Phase II Clinical Trial

Hypofractionated vs. Conventional Chemoradiotherapy After Induction Chemo-immunotherapy for Unresectable Esophageal Squamous Cell Carcinoma (NCT06912074) is a Phase 2 interventional studying Esophageal Squamous Cell Carcinoma (ESCC), sponsored by Sun Yat-sen University. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

This is a prospective, open-label, randomized phase II clinical trial designed to compare the efficacy and toxicity of hypofractionated concurrent chemoradiotherapy versus conventional fractionated concurrent chemoradiotherapy following induction chemoimmunotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma.

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Esophageal Squamous Cell Carcinoma (ESCC) 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 134 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 (ESCC) 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: - Pathologically or cytologically confirmed diagnosis of esophageal squamous cell carcinoma; - Evaluated as unresectable locally advanced esophageal squamous cell carcinoma by endoscopic ultrasound, imaging studies including esophagography, CT of the neck, chest, and upper abdomen, MRI of the neck and chest, whole-body bone scan, or PET/CT, with staging in the range of II-IVB (stage IVB limited to celiac lymph node or supraclavicular lymph node metastasis); - Male or female aged 18 to 80 years; - Eligible for oral drug therapy; - No prior chemotherapy, radiotherapy, surgery, targeted therapy, or immunotherapy; - Tumor sample requirement: Must provide adequate unstained, archived tumor tissue samples for analysis; - Expected survival ≥12 weeks; - Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1; - Postmenopausal women, or women with a negative urine or serum pregnancy test within 14 days before the study drug administration; - Women must not be breastfeeding; - Organ and bone marrow function must meet the following criteria: Forced expiratory volume in 1 second (FEV1) ≥1000 mL; Absolute neutrophil count ≥1.5 × 10\^9/L; platelet count at least 100 × 10\^9/L; blood count (hemoglobin) at least 90 g/L; Estimated glomerular filtration rate (eGFR) ≥50 mL/min based on the Cockcroft-Gault formula (Cockcroft and Gault, 1976); Serum bilirubin ≤1.5 × the upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN; - Signed and dated willing to sign a consent form must be provided before participation in any study procedures. Who Should NOT Join This Trial: Exclusion Criteria for Induction Treatment: - Participation in another clinical trial, unless it is an observational (non-interventional) study; ...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: * Pathologically or cytologically confirmed diagnosis of esophageal squamous cell carcinoma; * Evaluated as unresectable locally advanced esophageal squamous cell carcinoma by endoscopic ultrasound, imaging studies including esophagography, CT of the neck, chest, and upper abdomen, MRI of the neck and chest, whole-body bone scan, or PET/CT, with staging in the range of II-IVB (stage IVB limited to celiac lymph node or supraclavicular lymph node metastasis); * Male or female aged 18 to 80 years; * Eligible for oral drug therapy; * No prior chemotherapy, radiotherapy, surgery, targeted therapy, or immunotherapy; * Tumor sample requirement: Must provide adequate unstained, archived tumor tissue samples for analysis; * Expected survival ≥12 weeks; * Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1; * Postmenopausal women, or women with a negative urine or serum pregnancy test within 14 days before the study drug administration; * Women must not be breastfeeding; * Organ and bone marrow function must meet the following criteria: Forced expiratory volume in 1 second (FEV1) ≥1000 mL; Absolute neutrophil count ≥1.5 × 10\^9/L; Platelets ≥100 × 10\^9/L; Hemoglobin ≥90 g/L; Estimated glomerular filtration rate (eGFR) ≥50 mL/min based on the Cockcroft-Gault formula (Cockcroft and Gault, 1976); Serum bilirubin ≤1.5 × the upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN; * Signed and dated informed consent must be provided before participation in any study procedures. Exclusion Criteria: Exclusion Criteria for Induction Treatment: * Participation in another clinical trial, unless it is an observational (non-interventional) study; * Use of immunosuppressive drugs within 28 days prior to the first infusion of Toripalimab, excluding physiological doses of intranasal inhaled corticosteroids, prednisone ≤10 mg/day, or equivalent systemic corticosteroids; * Prior use of any anti-PD-1 or anti-PD-L1 antibody; * Major surgery within 4 weeks prior to entering the study (excluding vascular access procedures); * A history of autoimmune disease within the past 2 years; * Active or a history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis); * History of primary immunodeficiency; * History of organ transplantation requiring immunosuppressive treatment; * Uncontrolled complications, including but not limited to persistent or active infections, symptomatic congestive heart failure, poorly controlled hypertension, unstable angina, arrhythmias, active peptic ulcer disease or gastritis, active bleeding disorders, including any known HBsAg-positive patients with HBV DNA \>500 IU/ml, hepatitis C, or HIV, or any psychiatric or social conditions that would impair the ability to comply with study requirements or harm the patient's ability to provide written informed consent; * Receipt of a live attenuated vaccine within 30 days prior to study initiation or within 30 days after receiving Toripalimab; * History of another primary malignancy within 5 years prior to the initiation of Toripalimab treatment, excluding adequately treated skin basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ of the cervix; * Pregnancy, breastfeeding women, or men and women of reproductive potential who are not using effective contraception. Exclusion Criteria for Concurrent Chemoradiotherapy After Induction Treatment: * Development of distant metastasis (excluding celiac lymph node or supraclavicular lymph node metastasis); * Development of local regional progression, with the radiation oncologist assessing that the patient cannot receive definitive chemoradiotherapy due to normal tissue dose limitations; * PS score of 2-4; * Any of the following organ and bone marrow dysfunction criteria: FEV1 \<1000 mL; absolute neutrophil count \<1.5 × 10\^9/L; platelets \<100 × 10\^9/L; hemoglobin \<90 g/L; serum creatinine clearance \<50 mL/min according to the Cockcroft-Gault formula (Cockcroft \& Gault, 1976); serum bilirubin \>1.5 times the upper limit of normal (ULN); ALT and AST \>2.5 times ULN.

Treatments Being Tested

DRUG

Induction chemoimmunotherapy

All patients will receive two cycles of induction therapy with albumin-bound paclitaxel and cisplatin combined with toripalimab.

RADIATION

Hypofractionated Radiation Therapy

All patients will receive hypofractionated radiotherapy once daily, five days per week, followed by a boost. Three weeks after the completion of the first phase of hypofractionated radiotherapy, tumor response and cardiopulmonary function will be evaluated. For patients who achieve a partial response, have no deep esophageal ulcers on endoscopy, and have cardiopulmonary function tolerating the radiotherapy boost, a second phase of radiotherapy will be planned using a new CT simulation and radiotherapy design. First Phase of Radiotherapy: Total dose of 2500 cGy in 5 fractions (500 cGy per fraction) Second Phase of Radiotherapy: Total dose of 2500 cGy in 10 fractions (250 cGy per fraction) The interval between the two phases of radiotherapy will be 28 days.

RADIATION

Conventional Fractionated Radiation Therapy

Patients will receive a total dose of 5000 cGy in 25 fractions, with 200 cGy per fraction.

DRUG

Concurrent Chemotherapy

Capecitabine oral administration, 1000 mg/m², twice daily

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.

Sun yat-sen University Cancer Center

Guangzhou, Guangdong, China

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06912074), the sponsor (Sun Yat-sen University), 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 NCT06912074 clinical trial studying?

Who can participate in NCT06912074?

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 NCT06912074?

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 NCT06912074. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06912074. 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.