Toripalimab with Paclitaxel and Cisplatin As Neoadjuvant Treatment for Esophageal Squamous Cell Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Toripalimab
- Conditions
- Esophageal Squamous Cell Cancer
- Sponsor
- Peking University
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Pathologic complete response rate
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
Neoadjuvant chemoradiotherapy or chemotherapy followed by surgery is the standard treatment for local advanced esophageal cancer (EC). It had been demonstrated that patients who achieve pathologic complete response (pCR) after neoadjuvant treatment had better prognosis. However, the pCR rate were about only 5-10% in neoadjuvant chemotherapy and 20-40% in neoadjuvant concurrent chemoradiotherapy.
PD-1 antibody based immunotherapy alone as second-line treatment or combined with chemotherapy as first-line treatment had been proved that could prolong overall survival of EC patients. And a recent phase 3 clinical trial CheckMate 577 reported that, as adjuvant treatment, nivolumab could improve disease-free survival in EC and esophageal-gastric junction cancer.
The aim of this study was to evaluate the efficacy and safety of toripalimab, an anti-PD-1 antibody, combined with paclitaxel and cisplatin as neoadjuvant treatment in local advanced esophageal squamous cell carcinoma (ESCC). We hope this combining treatment would increase the pCR rate of neoadjuvant chemotherapy and improve survival of patients, and at the menatime avoid the adverse events of neoadjuvant radiotherapy. This study will provide valuable information for further clinical trials of both Toripalimab and other immune checkpoint inhibition agents in treatment of esophageal cancer.
Investigators
Xiaodong Zhang
Dean of VIP2 Gastrointestinal Cancer Division of Medical Department, Beijing Cancer Hospital
Peking University
Eligibility Criteria
Inclusion Criteria
- •Age: 18-70 years old, both gender.
- •Histopathologically confirmed esophageal squamous cell carcinoma.
- •No previous chemotherapy, radiotherapy, traditional Chinese medicine and other anti-tumor treatments.
- •Imaging (CT or MR) or ultrasound endoscopy confirmed local advanced resectable lesions ( AJCC 8th edition standard, stage 3N0M0 or T1-4aN+M0).
- •The ECOG performance status score of 0-
- •Normal functionof all major organs, that is:
- •Hemoglobin (Hb) ≥ 100g/L,
- •Neutrophils (ANC) ≥ 1.5×109/L, ③ Platelet count (PLT) ≥100×109/L, ④ Prothrombin time (PT) and partial prothrombin time (PTT) ≤ 1.5×upper limit of normal (ULN). (For the use of a stable dose of anticoagulant therapy such as low molecular weight heparin or warfarin, if the INR is within the expected therapeutic range of anticoagulants, patient could be screened); ⑤ Serum creatinine (Cr) ≤ 1.5 ×ULN, or 24-hour creatinine clearance rate \>60mL/min（Cockcroft-Gault）; ⑥ Total blood bilirubin (TB) ≤ 1.5ULN; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5×ULN; albumin (ALB) ≥ 30g/L.
- •The cardiac function is basically normal, the left ventricular ejection fraction is ≥50%, and the blood pressure is under controlled within 140/90 mmHg before enrollment.
- •Pulmonary function is basically normal, without moderate to severe obstructive and diffuse dysfunction.
Exclusion Criteria
- •Adenocarcinoma, small cell carcinoma, and other non-squamous cell carcinoma types of esophageal cancer.
- •Imaging examinations (CT or MRI) or endoscopic ultrasonography revealed early stage esophageal cancer, including: carcinoma in situ (Tis), lesions only invaded the mucosa layer or the muscularis propria without lymph node metastasis (T1-2N0).
- •Imaging examinations (CT or MRI) revealed unresectable disease including invasion of vertebral body, aorta, and organs (T4b), or with distant metastases such as lungs, liver, bones and other organ metastases (M1) ;
- •Imaging (esophagography, CT or MR) examination within 4 weeks before enrollment revealed esophageal mediastinal fistula or esophagotracheal fistula.
- •Gastrointestinal bleeding such as hematemesis or melena within 4 weeks before the first dose of treatment.
- •Allergic to PD-1 antibodies, paclitaxel, or cisplatin.
- •Receiving previous anti-tumor treatments such as chemotherapy, radiotherapy, molecular targeted therapy, or Chinese medicine treatment within 4 weeks before enrollment.
- •Receiving corticosteroids (\>10 mg prednisone or equivalent dose per day) or other immunosuppressive therapy within 2 weeks before enrollment, except for those who use corticosteroids to prevent allergies, nausea, and vomiting.
- •Received live vaccines within 4 weeks before the first dose of treatment.
- •Receiving major surgery or suffered severe trauma within 4 weeks before the first dose of treatment.
Arms & Interventions
TPC treatment
Neoadjuvant treatment of toripalimab, paclitaxel and cisplatin
Intervention: Toripalimab
TPC treatment
Neoadjuvant treatment of toripalimab, paclitaxel and cisplatin
Intervention: Paclitaxel
TPC treatment
Neoadjuvant treatment of toripalimab, paclitaxel and cisplatin
Intervention: Cisplatin
Outcomes
Primary Outcomes
Pathologic complete response rate
Time Frame: Three weeks after surgery of last enrolled subject. Estimate up to 2 years
The rate of pathologic complete response rate after neoadjuvant therapy.
Secondary Outcomes
- Disease-free survival(From date of surgery until the date of death from any cause or the date of first documented disease progression whichever came first. Estimate up to three years.)
- Objective Response Rate(One month after 2 cycles' treatment of last enrolled subject. Estimate up to 2 years)
- Adverse events(From enrollment to 60 days after the end protocol treatment)
- Major pathologic response rate(Three weeks after surgery of last enrolled subject. Estimate up to 2 years.)
- Overall survival(From enrollment to death of patients. Estimate up to 5 years.)
- R0 resection rate(Three weeks after surgery of last enrolled subject. Estimate up to 2 years)