Comparing two types of chemoradiotherapy for advanced esophageal cancer

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

This study is testing whether a new way of giving chemotherapy and radiation can help people with advanced esophageal cancer feel better and stay safe compared to the standard method.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 134 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: Toripalimab, chemotherapy, immunotherapy, radiation, prednisone
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06912074 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness and safety of hypofractionated concurrent chemoradiotherapy compared to conventional fractionated concurrent chemoradiotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma. Participants will first receive induction therapy with a combination of albumin-bound paclitaxel, cisplatin, and toripalimab. Afterward, they will be randomly assigned to one of the two chemoradiotherapy approaches. The study will monitor patients for efficacy and safety outcomes following treatment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 80 with unresectable locally advanced esophageal squamous cell carcinoma who have not received prior chemotherapy or radiotherapy.

Not a fit: Patients with resectable esophageal cancer or those who have previously undergone chemotherapy or radiotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective treatment option for patients with advanced esophageal cancer.

How similar studies have performed: Previous studies have explored various chemoradiotherapy regimens, but this specific comparison of hypofractionated versus conventional approaches is relatively novel.

Eligibility criteria

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.

Where this trial is running

Guangzhou, Guangdong

• Sun yat-sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Hui Liu, Professor — Sun yat-sen universtiy cancer center
• Study coordinator: Bo Qiu

Conditions Esophageal Squamous Cell Carcinoma; Hypofractionated Concurrent Chemoradiotherapy; Conventional Fractionated Concurrent Chemoradiotherapy; Induction chemoimmunotherapy