Esophageal Squamous Cell Carcinoma (ESCC)
Conditions
Keywords
Adebrelimab, chemotherapy, neoadjuvent, immune checkpoint inhibitor, borderline resectable
Brief summary
This clinical trial aims to preliminarily evaluate the efficacy and safety of adebrelimab combined with albumin-bound paclitaxel and carboplatin as neoadjuvant therapy for borderline resectable locally advanced esophageal squamous cell carcinoma (ESCC). The primary research objectives are to increase the R0 resection rate in such patients, thereby reducing the recurrence rate and improving overall survival (OS), as well as avoiding adverse reactions associated with radiotherapy.
Detailed description
Study participants shall complete the informed consent process and undergo multidisciplinary team (MDT) review for esophageal cancer. Patients confirmed as having borderline resectable disease and meeting all inclusion/exclusion criteria will be enrolled and receive treatment with adebrelimab plus albumin-bound paclitaxel and carboplatin. The treatment regimen is administered in 3-week cycles. Efficacy evaluation will be performed after 2 cycles: If the disease converts to resectable status, radical surgery will be conducted. If the disease is assessed as unresectable (progressive disease \[PD\] / stable disease \[SD\]), patients will receive definitive chemoradiotherapy or first-line treatment for advanced disease. If partial tumor regression is observed but the tumor remains unresectable, a third treatment cycle will be administered, followed by another efficacy evaluation. If the disease becomes resectable after the third cycle, radical surgery will be performed; if still unresectable (PD/SD), definitive chemoradiotherapy or first-line treatment for advanced disease will be given. For patients who achieve R0 resection, the investigator will determine the necessity of adjuvant therapy based on individual patient conditions. Patients with R1/R2 resection will receive concurrent chemoradiotherapy. If the MDT determines that radical resection is not feasible, patients will receive definitive concurrent chemoradiotherapy.
Interventions
Study participants shall complete the informed consent process and undergo multidisciplinary team (MDT) review for esophageal cancer. Patients confirmed as having borderline resectable disease and meeting all inclusion/exclusion criteria will be enrolled and receive treatment with adebrelimab plus albumin-bound paclitaxel and carboplatin.The treatment regimen is administered in 3-week cycles. Efficacy evaluation will be performed after 2 cycles.
Sponsors
Sun Yat-sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1.Voluntarily participate in the study and sign the written informed consent form. 2.Aged between 18 and 75 years old. 3.Histologically confirmed thoracic esophageal squamous cell carcinoma without distant metastasis. Patients are defined as borderline resectable after enhanced computed tomography (CT), and/or endoscopic ultrasonography (EUS), endobronchial ultrasonography (EBUS) and multidisciplinary team (MDT) discussion. 4.No prior chemotherapy or radiotherapy. 5.Estimated overall survival of no less than 3 months. 6.Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1. 7.Hematological parameters (tested within 7 days): Hemoglobin (Hb) ≥ 90 g/L; Neutrophil count (NE) ≥ 1.5×10⁹/L; Platelet count (PLT) ≥ 100×10⁹/L. 8.Hepatic and renal function (tested within 7 days): Total bilirubin ≤ 1.5 × upper limit of normal (ULN); Creatinine ≤ 1.5 × ULN; Aspartate transaminase (AST)/Alanine transaminase (ALT) ≤ 2.5 × ULN; Alkaline phosphatase (ALP) ≤ 5.0 × ULN. 9.Absence of severe complications, including active massive gastrointestinal bleeding, perforation, jaundice, intestinal obstruction, and non-neoplastic fever above 38°C. 10.Fertile patients must adopt effective contraceptive measures throughout the study period. 11.Good treatment compliance, and able to complete follow-up assessments for efficacy and adverse events as required by the protocol.
Exclusion criteria
1. Patients with cervical esophageal squamous cell carcinoma. 2. Patients with distant metastasis. 3. Patients with nearly complete esophageal obstruction confirmed by endoscopy who require interventional therapy for decompression. 4. Patients with prior placement of esophageal or tracheal stents. 5. Patients with high risk of bleeding or perforation due to obvious tumor invasion into adjacent vital organs (major arteries or trachea), or patients with existing fistula formation. 6. Patients with other concurrent primary malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix). 7. Use of immunosuppressive drugs within 1 week prior to enrollment. This exclusion does not apply to intranasal, inhaled or other topical glucocorticoids, systemic glucocorticoids at physiological doses (i.e., prednisone ≤ 10 mg/day or equivalent), or glucocorticoids administered for contrast medium allergy prophylaxis. 8. Active autoimmune diseases requiring symptomatic treatment, or a medical history of such diseases within the past 2 years. 9. Known history of primary immunodeficiency. 10. Confirmed active tuberculosis. 11. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation. 12. Interstitial lung disease requiring corticosteroid therapy. 13Known allergy to any monoclonal antibody, chemotherapeutic agents (taxanes, carboplatin), or their excipients. 14.Severe cardiac diseases, including documented congestive heart failure, uncontrolled high-risk arrhythmia, medically treated angina pectoris, clinically significant valvular heart disease, history of severe myocardial infarction, and refractory hypertension. 15.Chronic diarrhea (≥4 watery stools per day) or renal insufficiency. 16.Active infection or active communicable diseases. 17.Neurological or psychiatric disorders impairing cognitive function. 18.Pregnant or breastfeeding women. 19.Other acute or chronic diseases, psychiatric disorders or abnormal laboratory findings that, in the investigator's judgment, may increase risks related to study participation or study drug administration, or interfere with the interpretation of study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| R0 resection rate | From patient enrollment to two weeks post-surgery | The proportion of patients with tumor margins showing no residual cancer cells under the microscope after surgical resection. That is, the proportion of patients in PPS achieving R0 resection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | up to 5 years post-surgery | OS is the time interval from the start of treatment to death due to any reason or loss of follow-up |
| Progression free survival | up to 5 years post-surgery | Disease free survival (DFS) refers to the time from the start of treatment until disease recurrence or death from any cause, whichever occurs first. |
| Pathologic complete response rate | From patient enrollment to two weeks post-surgery | — |
| Incidence of perioperative complications | from the first drug administration to within 30 days after the last intended treatment | — |
| Tumor Regression Grade | From patient enrollment to two weeks post-surgery | — |
Countries
China
Contacts
CONTACTHong Yang, MD, PhD
CONTACTChief physician
Outcome results
None listed