JCOG2206: A randomized controlled phase III study comparing surgery alone versus adjuvant nivolumab versus adjuvant S-1 for locally advanced esophageal squamous cell carcinoma with no pathological complete response after neoadjuvant chemotherapy followed by curative esophagectomy

JRCT ID: jRCTs031230219

Registered date:11/07/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Esophageal squamous cell carcinoma with no pathological complete response after neoadjuvant therapy
• Date of first enrollment: 06/09/2023
• Target sample size: 450
• Study type: Interventional

Intervention(s)

Arm A: Neoadjuvant chemotherapy followed by curative esophagectomy
Arm B: Neoadjuvant chemotherapy followed by curative esophagectomy and postoperative chemotherapy with Nivolumab (240 mg/body (day 1) every 2 weeks or 480 mg/body (day 1), up to 1 year)
Arm C: Neoadjuvant chemotherapy followed by curative esophagectomy and postoperative chemotherapy with S-1(50-120 mg/body (day1-28) every 6 weeks, up to 4 cycles)

Outcome(s)

• Primary Outcome: Relapse free survival
• Secondary Outcome: Disease free survival, overall survival, toxicities and incremental cost-effectiveness ratio

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 80age old
• Gender: Both

Include criteria

(1) Histologically proven esophageal squamous cell carcinoma, adenosquamous carcinoma, or basaloid cell carcinoma.
(2) All lesions including primary tumor located in the thoracic esophagus.
(3) Multiple tumors are eligible. Secondary lesion in the cervical esophagus which is indicated for endoscopic resection (EMR/ESD) is eligible.
(4) Clinical stage I (except for T1N0), II, III, IVA (except for T4), IVB (only supraclavicular lymph node metastasis except for T4) based on the cervical to abdominal contrast-enhanced CT (UICC-TNM 8th edition). After staging, patients received neoadjuvant chemotherapy (less than 3 courses of DCF or 2 courses of CF).
(5) Right-thoracoabdominal esophagectomy with D2 or higher lymph node dissection including minimally invasive procedure (thoracoscopy, laparoscopy, and robot-assisted) was accomplished within 21 to 90 days after neoajuvant chemotherapy.
(6) R0 resection was performed.
(7) Diagnosed with ypstage T0-4aN1-3M0, T1-4aN0M0, T0-4aNanyM1 (only supraclavicular lymph node metastasis) by surgical specimens (UICC-TNM 8th edition).
(8) Age between 18 and 80 at registration.
(9) Performance Status (ECOG) 0 or 1.
(10) Within 28 to 84 days after esophagectomy.
(11) No prior endocrine therapy, chemotherapy, molecular targeted therapy, and immunotherapy against any other malignancies within 5 years, and no prior cervical and thoracic radiotherapy for other malignancies. Hormone therapy for breast cancer or prostate cancer is eligible.
(12) No active autoimmune disease and no history of chronic or recurrent autoimmune disease.
(13) Sufficient organ function
i) Neutrophil >= 1,200/mm3
ii) Hb >= 8.0 g/dL
iii) Platelet >= 75,000/mm3
iv) T.Bil <= 2.0 mg/dL
v) AST <= 100 U/L
vi) ALT <= 100 U/L
vii) SpO2 >= 95%(room air)
viii) CCr >= 50 mL/min
(14) Written informed consent from patient

Exclude criteria

(1) Synchronous or metachronous (within 5 years) malignancies.
(2) Infectious disease requiring systemic treatment.
(3) Body temperature of 38 degrees Celsius or higher.
(4) Female during pregnancy, within 28 days of postparturition, or during lactation. Males with partners planning conception shortly.
(5) Psychological disorder difficult to participate in this clinical study.
(6) Receiving continuous systemic corticosteroid with a prednisolone equivalent greater than 10 mg/day, immunosuppressant treatment or immunoglobulin.
(7) Under treatment with flucytosine, phenytoin, or warfarin.
(8) Positive for HBs antigen or HIV antigen.
(9) Uncontrolled diabetes mellitus.
(10) Uncontrolled arterial hypertension.
(11) History of unstable angina pectoris within 3 weeks or myocardial infarction within 6 months before registration.
(12) Uncontrolled valvular disease, dilated cardiomyopathy, and hypertrophic cardiomyopathy.
(13) Severe emphysema, interstitial pneumonia, or pulmonary fibrosis based on chest CT.

Related Information

• Primary Sponsor: KITAGAWA Yuko
• Source(s) of Monetary Support: National Cancer Center Japan,Japan Agency for Medical Research and Development