None listed
Conditions
Interventions
Drug, Radiation : Adjuvant therapy arm
• For participants who underwent upfront surgery without prior neoadjuvant therapy or those who underwent neoadjuvant chemotherapy followed by surgery, the choi
Sponsors
Asan Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Be willing and able to provide written informed consent. 2) Be =19 years of age on the day of signing the informed consent form. 3) Have ECOG performance status 0 or 1 (Appendix 1). 4) Have a histologically confirmed diagnosis of squamous cell carcinoma of esophagus. • Patients with tumors of mixed histology (i.e., squamous and non-squamous) are eligible if the predominant histological component is squamous, except when small cell or neuroendocrine elements are present. 5) Must have completed surgical resection for localized disease, either with prior neoadjuvant therapy (chemotherapy or chemoradiotherapy) or without prior neoadjuvant therapy (i.e., upfront surgery), in accordance with the 8th edition of the AJCC staging system (Appendix 2). Exceptionally, cases with supraclavicular lymph node metastasis as the only M1 lesion are also eligible if the lymph node has been surgically removed. 6) Must have undergone curative surgery (R0 resection) with negative margins on the resected specimen. 7) Complete resection must have been performed between 4-16 weeks before randomization. 8) Must have a documented disease-free status based on a complete physical examination and imaging studies within 4 weeks before randomization. Imaging studies must include CT scans (or MRI) of the chest, abdomen, and pelvis. 9) Must provide tumor tissue from pre-treatment biopsy (i.e., a biopsy obtained prior to neoadjuvant therapy in cases where neoadjuvant therapy is followed by surgery) or from surgical specimens and baseline blood samples for post-surgery ctDNA MRD measurement. • For patients who underwent upfront surgery, surgical tissue is preferred. • For those who received neoadjuvant therapy followed by surgery, pre-treatment biopsy tissue is required. If pre-treatment biopsy tissue is unavailable or inadequate, submission of surgical specimens may be permitted following approval by the Study Sponsor. • A FFPE tumor specimen in a paraffin block or 20 (at least 10, with a thickness of 10 µm) freshly cut unstained FFPE slides, along with one H&E-stained slide, must be submitted with the associated pathology report. If an insufficient number of slides is available, the decision on patient enrollment can be made in consultation with the Study Sponsor. • Peripheral blood of approximately 4 mL must be collected for germline DNA analysis. • Peripheral blood of approximately 20 mL must be collected between 3 to 12 weeks after curative surgery for ctDNA testing. 10) Must be confirmed to have MRD-positive status via postoperative baseline ctDNA testing. 11) Must have adequate major organ functions as demonstrated by the following laboratory results obtained within 14 days before randomization (these criteria must also be met within 7 days before initiating study treatment in the adjuvant therapy arm): • Adequate bone marrow function defined by: – Absolute neutrophil count (ANC) = 1,500/µL without granulocyte-colony stimulating factor support within 7 days before testing – Platelet count = 100 ×103/µL without transfusion within 7 days before laboratory testing • Adequate renal function defined by: – Serum creatinine = 1.5 x upper limit of normal (ULN) or creatinine clearance =50 mL/minute, calculated using the Cockcroft-Gault formula (Appendix 3) or measured by a 24-hour urine collection • Adequate hepatic function defined by: – alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 x ULN – Total bilirubin = 1.5 x ULN, except for subjects w
Exclusion criteria
Exclusion criteria: 1) Documented recurrence of esophageal cancer before randomization following curative resection. 2) Receipt of any treatment aimed at the resected esophageal cancer after curative surgery, including chemotherapy, targeted therapy, immunotherapy, radiotherapy, biologic therapy, investigational agent, or local therapies, except for procedures intended for palliative care (e.g., stent insertion, balloon dilatation, or feeding enterostomy). 3) Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 inhibitor, or any other drug targeting T-cell co-stimulation or checkpoint pathways. 4) Active autoimmune disease requiring systemic treatment within the 2 years prior to study entry (i.e., using disease-modifying agents, corticosteroids, or immunosuppressive drugs). • Replacement therapy (e.g., thyroxine for autoimmune-related hypothyroidism, insulin for type1 diabetes mellitus, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. 5) Condition requiring systemic treatment with corticosteroids (>10 mg daily prednisone or equivalent) or any other form of immunosuppressive therapy within 14 days prior to study entry: • Use of topical, ocular, intra-articular, intranasal, and inhaled corticosteroids is permitted if there is no active autoimmune disease. • A short course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted. 6) Receipt of a live vaccine within 28 days prior to study entry. • COVID-19 vaccines are allowed except for any live vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. 7) Active infection requiring systemic therapy within 14 days prior to study entry. 8) History of severe hypersensitivity to paclitaxel, carboplatin, or any antibody products. 9) Known history of, or any evidence of interstitial lung disease, non-infectious pneumonitis, or pulmonary fibrosis diagnosed based on imaging or clinical findings. • Subjects with radiation pneumonitis may be enrolled if radiation pneumonitis is stable (beyond acute phase) and unlikely to recur. 10) History of allogeneic stem cell or solid organ transplantation. 11) Malignancies other than esophageal cancer within the 3 years prior to study entry, except for malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival rate >90%), such as adequately treated non-melanoma skin cancer, superficial bladder cancer, or carcinoma in situ (e.g., of cervix, breast, or prostate). • Subjects who received endoscopic mucosal resection or dissection for superficial mucosal cancers within the past 3 years are eligible. 12) Subjects with toxicities attributed to prior anti-cancer therapy, except alopecia, anorexia, fatigue, and hearing loss, that have not resolved to Grade 1 (NCI CTCAE v5.0) or baseline before randomization will be excluded. 13) Significant cardiovascular impairment within 6 months prior to study entry, including a history of congestive heart failure (New York Heart Association Class III or IV), unstable angina, myocardial infarction, cerebrovascular accident, or cardiac arrhythmia associated with hemodynamic instability. 14) Any serious or uncontroll
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Recurrence-free survival as assessed by the investigator | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival ;Distant metastasis-free survival;Locoregional Recurrence-free survival;Pattern of first recurrence;The incidence and severity of adverse events according to NCI-CTCAE v5.0;PROs-measured Health-related quality of life (HRQoL);Clearance, time to clearance, and longitudinal changes in ctDNA during and after adjuvant treatment as a predictive biomarker for treatment efficacy, and during surveillance as a prognostic biomarker;ctDNA levels as a predictive biomarker for treatment efficacy and as a prognostic biomarker | — |
Countries
Korea, Republic of
Contacts
Public ContactSook Ryun Park
Asan Medical Center
Outcome results
None listed