A Phase II Clinical Study of Sintilimab Combined with Chemotherapy Followed by Concurrent Chemoradiotherapy for Locally Advanced Unresectable Esophageal Squamous Cell Carcinoma (ESCC) (NICE-CS)

Shanghai Chest Hospital1 site in 1 country52 target enrollmentNovember 1, 2024

Overview

Brief Summary

This is a prospective, single-arm, phase II clinical study designed to evaluate the efficacy and safety of sintilimab combined with chemotherapy, followed by sequential concurrent chemoradiotherapy as conversion therapy, in treatment-naïve esophageal squamous cell carcinoma (ESCC) patients with cT4bN-/+M0 and/or cTanyN+M0 staging (including those with extracapsular invasion of mediastinal lymph nodes).

Registry

clinicaltrials.gov

Start Date

November 1, 2024

End Date

December 31, 2028

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Shanghai Chest Hospital

Responsible Party

Principal Investigator

Jun Liu

associate professor

Shanghai Chest Hospital

Eligibility Criteria

Inclusion Criteria

•Signed written informed consent prior to the initiation of any study-related procedures.
•Age: ≥20 years and ≤75 years, no gender restrictions.
•Diagnosed with esophageal squamous cell carcinoma (ESCC) based on histopathology and imaging, with clinical staging of cT4bN-/+M0 and/or cTanyN+M0 (extracapsular invasion of mediastinal lymph nodes).
•Thoracic segment esophageal squamous cell carcinoma.
•Primary lesion is inoperable or inoperable due to extracapsular invasion of mediastinal lymph nodes.
•ECOG performance status (PS) of 0-
•Estimated survival time ≥6 months.
•No prior antitumor therapy for esophageal cancer, including but not limited to chemotherapy, radiotherapy, targeted therapy, or immunotherapy.
•At least one measurable lesion as per RECIST 1.1 criteria.
•No surgical contraindications based on preoperative evaluation of organ function.

Exclusion Criteria

•Diagnosis of malignancies other than esophageal cancer within 5 years prior to the first dose of the investigational drug (excluding radically treated basal cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the lung, or T1a non-invasive adenocarcinoma).
•Patients with existing or high-risk tracheoesophageal or aortoesophageal fistulas.
•Presence of distant metastases.
•Current participation in an interventional clinical study or receipt of other investigational drugs or devices within 4 weeks prior to the first dose.
•Prior treatment with anti-PD-1, anti-PD-L1, or any other agents targeting stimulatory or co-inhibitory T-cell receptors (e.g., CTLA-4, OX-40, CD137).
•Receipt of systemic antitumor traditional Chinese medicine or immunomodulatory drugs (including thymosin, interferon, or interleukin) within 2 weeks prior to the first dose, except for local use to control pleural effusion.
•Active autoimmune disease requiring systemic therapy (e.g., disease-modifying agents, corticosteroids, or immunosuppressive drugs) within 2 years prior to the first dose, excluding replacement therapy (e.g., thyroid hormone, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency).
•Use of systemic corticosteroids (excluding nasal, inhaled, or other locally administered corticosteroids) or other immunosuppressive drugs within 7 days prior to the first dose, except for physiological doses of corticosteroids (≤10 mg/day prednisone or equivalent).
•History of allogeneic organ transplantation (excluding corneal transplantation) or allogeneic hematopoietic stem cell transplantation.
•Known hypersensitivity to active ingredients or excipients in the investigational product.

Arms & Interventions

Experimental Arm

Eligible participants will first receive two cycles of sintilimab in combination with liposomal paclitaxel and cisplatin. After two cycles, an evaluation will be conducted. Patients deemed eligible for surgery will undergo surgical resection, followed by up to one year of adjuvant sintilimab. The necessity of postoperative adjuvant radiotherapy will be determined by the investigator. For patients deemed ineligible for surgery, concurrent chemoradiotherapy will be administered. Four weeks after the completion of concurrent chemoradiotherapy, a second surgical evaluation will be performed. Patients eligible for surgery at this stage will undergo surgical resection followed by adjuvant sintilimab treatment. Those who remain ineligible for surgery will continue sintilimab treatment after concurrent chemoradiotherapy.

Intervention: Sintilimab

Experimental Arm

Eligible participants will first receive two cycles of sintilimab in combination with liposomal paclitaxel and cisplatin. After two cycles, an evaluation will be conducted. Patients deemed eligible for surgery will undergo surgical resection, followed by up to one year of adjuvant sintilimab. The necessity of postoperative adjuvant radiotherapy will be determined by the investigator. For patients deemed ineligible for surgery, concurrent chemoradiotherapy will be administered. Four weeks after the completion of concurrent chemoradiotherapy, a second surgical evaluation will be performed. Patients eligible for surgery at this stage will undergo surgical resection followed by adjuvant sintilimab treatment. Those who remain ineligible for surgery will continue sintilimab treatment after concurrent chemoradiotherapy.

Intervention: Chemotherapy

Experimental Arm

Eligible participants will first receive two cycles of sintilimab in combination with liposomal paclitaxel and cisplatin. After two cycles, an evaluation will be conducted. Patients deemed eligible for surgery will undergo surgical resection, followed by up to one year of adjuvant sintilimab. The necessity of postoperative adjuvant radiotherapy will be determined by the investigator. For patients deemed ineligible for surgery, concurrent chemoradiotherapy will be administered. Four weeks after the completion of concurrent chemoradiotherapy, a second surgical evaluation will be performed. Patients eligible for surgery at this stage will undergo surgical resection followed by adjuvant sintilimab treatment. Those who remain ineligible for surgery will continue sintilimab treatment after concurrent chemoradiotherapy.

Intervention: radiotherapy