A Randomized, Open-label, Phase II Study of PD-1 Inhibitor Combined With Neoadjuvant Chemotherapy Versus Neoadjuvant Chemoradiotherapy in Subjects With Resectable Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- PD-1 inhibitor
- Conditions
- Esophageal Neoplasms
- Sponsor
- Fujian Cancer Hospital
- Enrollment
- 92
- Locations
- 6
- Primary Endpoint
- Pathologic complete response (pCR) rate
- Last Updated
- 4 years ago
Overview
Brief Summary
The purpose of this study is to explore the efficacy and safety of compare the efficacy and safety of PD-1 inhibitor and chemotherapy（treatment group） with chemoradiotherapy（control group） in neoadjuvant treatment of resectable thoracic esophageal squamous cell carcinoma.
Detailed Description
This is a randomized, open-label, phase II study of PD-1 inhibitor combined With neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy in subjects With resectable locally advanced thoracic esophageal squamous cell carcinoma. The patients will be divided into two groups(1:1). In the treatment group, PD-1 inhibitor ,albumin-bound paclitaxel and cisplatin will be given every 3 weeks for 2-4 cycles as neoadjuvant therapy. In the control gourp, albumin-bound paclitaxel and cisplatin will be given every 3 weeks for 2 cycles as neoadjuvant therapy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Volunteered to participate in the study, signed the informed consent form;
- •Histologically or cytological confirmed esophageal squamous cell carcinoma;
- •Patients with resectable disease of primary tumor in thoracic esophagus (cT1b-4aN1-3M0, cT3-4aN0M0) evaluated by CT/MRI/EUS;
- •Expected R0 resection;
- •Aged 18-75 years, male or female;
- •ECOG PS 0-1;
- •Without prior treatments including surgery, chemotherapy, radiotherapy, and targeting treatment for esophageal cancer;
- •Surgery is planned after neoadjuvant treatment;
- •Without any contraindication of operation;
- •Adequate organ function as follows: 1) Routine blood test: Leukocytes \>=3.0x10\^9/L; Absolute neutrophil count \>=1.0x10\^9/L; Platelet \>=80x10\^9/L; Hemoglobin \>=90 g/L; 2) Blood biochemical test: Total bilirubin \<=1.5 ULN; ALT \<=2.5 ULN; AST \<=2.5 ULN; Serum creatinine \<=1.5 ULN or creatinine clearance rate \>=50 mL/min (Cocheroft-Gault); 3) Coagulation function test: INR \<=1.5 ULN; APTT \<=1.5 ULN;
Exclusion Criteria
- •The tumor invades the adjacent organs of the esophageal lesion (aorta or trachea);
- •Patients with supraclavicular lymph node metastasis;
- •Uncontrollable pleural effusion, pericardial effusion or ascites requiring repeated drainage;
- •Poor nutritional status, BMI \< 18.5 Kg/m2; If corrected after nutritional support before randomization, enrollment can be further considered after evaluation by the principal investigator;
- •Has a history of allergy to monoclonal antibody, any component of PD-1 Inhibitor, paclitaxel, cisplatin or other platinum drugs;
- •Has received or is receiving any of the following treatments: A)any anti-tumor radiation, chemotherapy or other treatment drugs; B) Immunosuppressive drugs or whole-body hormone drugs are being used for immunosuppressive purposes within 2 weeks prior to the first use of the study drug (dose \> 10mg/ day prednisone or equivalent dose);Inhalation or topical use of steroids and 10 mg/ day prednisone or equivalent dose of adrenocortical hormone replacement is permitted in the absence of active autoimmune disease; C) Received attenuated vaccine within 4 weeks before the first use of the study drug; D) Major surgery or severe trauma within 4 weeks prior to the first use of the study drug;
- •History of any active autoimmune disease, including but not limited to: interstitial pneumonia, enteritis, hepatitis, hypohysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (may be considered after hormone replacement therapy);Patients with psoriasis or childhood asthma/allergy who have been in complete remission and do not need any intervention as adults may be considered for inclusion, but patients requiring medical intervention with bronchodilators may not be included;
- •History of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency disease, or history of organ transplantation or allogeneic bone marrow transplantation;
- •Present of poorly controlled cardiac symptoms or disease, including but not limited to: (1) heart failure with NYHA class II or above (2) unstable angina, （3）myocardial infarction occurred within 1 year (4) clinical significance supraventricular or ventricular arrhythmias without clinical intervention or poorly controlled after clinical intervention;
- •Severe infection (CTCAE \> 2) occurred within 4 weeks prior to the first use of the study drug, such as severe pneumonia, bacteremia, infection complications requiring hospitalization, etc.;Baseline chest imaging indicated active pulmonary inflammation, infection signs and symptoms within 14 days prior to the first use of the study drug, or the need for oral or intravenous antibiotic treatment, except prophylactic antibiotic usage;
Arms & Interventions
PD-1 Inhibitor+albumin-bound paclitaxel+cisplatin
Participants receive PD-1 Inhibitor 200mg on Day 1 every 3 weeks (Q3W), albumin-bound paclitaxel 125 mg/m\^2 on Day 1, 8 Q3W, and cisplatin 75 mg/m\^2 on Day 1 Q3W, a total of 2-4 cycles，followed by surgery.
Intervention: PD-1 inhibitor
PD-1 Inhibitor+albumin-bound paclitaxel+cisplatin
Participants receive PD-1 Inhibitor 200mg on Day 1 every 3 weeks (Q3W), albumin-bound paclitaxel 125 mg/m\^2 on Day 1, 8 Q3W, and cisplatin 75 mg/m\^2 on Day 1 Q3W, a total of 2-4 cycles，followed by surgery.
Intervention: Albumin-Bound Paclitaxel
PD-1 Inhibitor+albumin-bound paclitaxel+cisplatin
Participants receive PD-1 Inhibitor 200mg on Day 1 every 3 weeks (Q3W), albumin-bound paclitaxel 125 mg/m\^2 on Day 1, 8 Q3W, and cisplatin 75 mg/m\^2 on Day 1 Q3W, a total of 2-4 cycles，followed by surgery.
Intervention: Cisplatin
Albumin-bound paclitaxel+cisplatin+radiotherapy
Participants receive albumin-bound paclitaxel 125 mg/m\^2 on Day 1, 8 Q3W, and cisplatin 75 mg/m\^2 on Day 1 Q3W, a total of 2 cycles combined with radiotherapy(40Gy/2Gy),followed by surgery.
Intervention: Albumin-Bound Paclitaxel
Albumin-bound paclitaxel+cisplatin+radiotherapy
Participants receive albumin-bound paclitaxel 125 mg/m\^2 on Day 1, 8 Q3W, and cisplatin 75 mg/m\^2 on Day 1 Q3W, a total of 2 cycles combined with radiotherapy(40Gy/2Gy),followed by surgery.
Intervention: Cisplatin
Albumin-bound paclitaxel+cisplatin+radiotherapy
Participants receive albumin-bound paclitaxel 125 mg/m\^2 on Day 1, 8 Q3W, and cisplatin 75 mg/m\^2 on Day 1 Q3W, a total of 2 cycles combined with radiotherapy(40Gy/2Gy),followed by surgery.
Intervention: Radiation
Outcomes
Primary Outcomes
Pathologic complete response (pCR) rate
Time Frame: Within 14 working days after surgery
Secondary Outcomes
- R0 resection rate(Within 14 working days after surgery)
- Overall Survival (OS)(Up to 8 years)
- Disease Free Survival (DFS)(Up to 8 years)