Patients diagnosed with locally advanced esophageal squamous cell carcinoma (ESCC) that is deemed unresectable face a bleak prognosis. Recent phase 1/2 studies have demonstrated the efficacy and safety of augmenting neoadjuvant concurrent chemoradiotherapy with immunotherapy in treating resectable ESCC. The present study is a prospective, 3-arm, randomized trial that seeks to evaluate the efficacy of diverse conversion therapy modalities in patients with unresectable ESCC. The study objectives include R0 resection rate, treatment-related adverse events, morbidity and mortality, 1-year progression-free survival (PFS), and 1-year overall survival (OS) rates. Tislelizumab is a humanized IgG4 monoclonal antibody with high affinity/specificity for programmed cell death protein 1 (PD-1). Tislelizumab was specifically engineered to minimize binding to FcɤR on macrophages, thereby abrogating antibody-dependent phagocytosis, a potential mechanism of T-cell clearance and resistance to anti-PD-1 therapy. This trial will provide valuable insights into the effectiveness of the three conversion therapy modalities and help to inform clinical decision-making for patients with unresectable locally advanced ESCC.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
90
Different sequences and methods of treatment to convert surgery
Department of Radiation Oncology, Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
Beijing, China
RECRUITINGR0 resection rate
Minimal distance tumor/circumferential resection margin (CRM) \> 1 mm.
Time frame: 4 months
1-year OS rate
Defined as the proportion of patients still alive within one year from treatment initiation.
Time frame: 1 year after all treatment
1-year PFS
Defined as the proportion of patients without disease progression or death within one year from treatment initiation.
Time frame: 1 year after all treatment
Positive rate of circulating tumor DNA (ctDNA) in minimal residual disease (MRD) before and after neoadjuvant treatment and its correlation with the pathological response and disease progression during surveilance
To investigate whether ctDNA variation can be used for MRD predicting incidence of pathological incidence and monitoring tumor progression after surgery
Time frame: 6 month
Incidence of Treatment-Emergent Adverse Events
Adverse event during chemoRT or immunotherapy
Time frame: 4 month
Pathological response rate
Time frame: 4 month
Postoperative complications
Time frame: 4 month
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