A Randomized, Double-blind, Parallel-controlled, Multicenter Phase III Clinical Study
Overview
- Phase
- Not Applicable
- Intervention
- Carrelizumab
- Conditions
- Esophageal Squamous Cell Carcinoma
- Sponsor
- The First Affiliated Hospital with Nanjing Medical University
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- PFS evaluated by IRC
- Status
- Enrolling By Invitation
- Last Updated
- 2 years ago
Overview
Brief Summary
This study is a randomized, double-blind, placebo-controlled, multicenter phase III clinical study to evaluate the efficacy and safety of carrelizumab plus concurrent chemoradiotherapy compared with placebo plus concurrent chemoradiotherapy in the treatment of patients with inoperably advanced esophageal cancer, and to explore the relationship between PD-L1 expression and efficacy in tumor tissues. Experimental group: carrelizumab in combination with concurrent chemoradiotherapy PD-1: carrelizumab: 200 mg/3W Chemotherapy: Paclitaxel: 50 mg/m2/W Cisplatin: 25mg/m2/W Radiotherapy: 50.4 Gy / 28 f Chemotherapy drugs are used for 5 cycles, and carrelibizumab is used for up to 24 months until PD or is intolerable Control group: placebo-resistant in combination with chemoradiotherapy placebo: 200 mg/3 W Chemotherapy: Paclitaxel: 50 mg/m2/W Cisplatin: 25mg/m2/W Radiotherapy: 50.4 Gy / 28 f Chemotherapy drugs are used for 5 cycles, and carrelibizumab is used for up to 24 months until PD or is intolerable
Detailed Description
Experimental group: carrelizumab in combination with concurrent chemoradiotherapy PD-1: carrelizumab: 200 mg/3W Chemotherapy: Paclitaxel: 50 mg/m2/W Cisplatin: 25mg/m2/W Radiotherapy: 50.4 Gy / 28 f Chemotherapy drugs are used for 5 cycles, and carrelibizumab is used for up to 24 months until PD or is intolerable Control group: placebo-resistant in combination with chemoradiotherapy placebo: 200 mg/3 W Chemotherapy: Paclitaxel: 50 mg/m2/W Cisplatin: 25mg/m2/W Radiotherapy: 50.4 Gy / 28 f Chemotherapy drugs are used for 5 cycles, and carrelibizumab is used for up to 24 months until PD or is intolerable
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients voluntarily participate in this study and sign informed consent;
- •Age 18-75 years, including 18 and 75 years old, male or female;
- •Patients with histologically confirmed locally advanced esophageal squamous cell carcinoma with a clinical stage of stage II-IVa that is inoperably resectable (including unresectable, or has contraindications to surgery or refuses surgery) (according to the 8th edition AJCC stage, the pre-treatment clinical stage is: cT1N2-3M0, cT2-4bN0-3M0);
- •the presence of measurable and/or non-measurable lesions that meet the definition of the Efficacy Evaluation Criteria for Solid Tumors (RECIST1.1);
- •Have not received systemic antineoplastic therapy (including but not limited to systemic chemotherapy, molecularly targeted therapy, immunotherapy, biological therapy, topical therapy, and other investigational therapies)
- •ECOG: 0\~1 point
- •Fresh or archived tumor tissue samples within 6 months (fresh samples preferred) must be provided for biomarker (such as PD-L1) analysis, the sample type is FFPE tumor tissue block or at least 5 unstained, 3-5 μm thick FFPE tumor tissue section, for subjects who cannot provide tissue samples that meet the above requirements, they can discuss with the sponsor to determine whether to enroll;
- •Expected survival≥ 3 months;
- •The function of vital organs meets the following requirements (no blood components and cell growth factors are allowed 2 weeks before starting screening tests):
- •Absolute neutrophil count (ANC) ≥1.5×109/L;
Exclusion Criteria
- •history of surgery for esophageal cancer;
- •history of previous fistula due to primary tumor invasion;
- •a higher risk of gastrointestinal bleeding, esophageal fistula, or esophageal perforation;
- •participants with poor nutritional status with a BMI of less than 18.5 kg/m2 or a PG-SGA score of ≥9;
- •have undergone major surgery or severe trauma within 4 weeks prior to the first use of the study drug;
- •presence of uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
- •Have received or are currently receiving any of the following treatments:
- •Anti-PD-1 or anti-PD-L1 antibody therapy, chemotherapy, radiotherapy, targeted therapy;
- •Have received any investigational drug within 4 weeks prior to the first use of the investigational drug;
- •Participants who require systemic therapy with corticosteroids (\> 10 mg prednisone equivalent per day) or other immunosuppressants within 2 weeks prior to the first study drug, except for local inflammation of the esophagus and for the prevention of allergies and nausea and vomiting. In other special circumstances, it is necessary to communicate with the sponsor. In the absence of active autoimmune disease, inhaled or topical steroid replacement and adrenocorticosteroid replacement at a dose \> a potent dose of 10 mg/day prednisone is allowed;
Arms & Interventions
Experimental group: carrelizumab in combination with concurrent chemoradiotherapy
Study drugs were administered intravenously on the first day of each cycle. Administered sequentially: carrelizumab, 200mg/time, paclitaxel, 50mg/m2, cisplatin, 25mg/m2, chemotherapy once a week, a total of 5 doses, carrelizumab every three weeks until PD or intolerable, up to 2 years, simultaneous radiotherapy at the first dose, the total dose of radiotherapy is 50.4Gy, completed in 28 divided doses, 1.8Gy each time, 5 times a week.
Intervention: Carrelizumab
Experimental group: carrelizumab in combination with concurrent chemoradiotherapy
Study drugs were administered intravenously on the first day of each cycle. Administered sequentially: carrelizumab, 200mg/time, paclitaxel, 50mg/m2, cisplatin, 25mg/m2, chemotherapy once a week, a total of 5 doses, carrelizumab every three weeks until PD or intolerable, up to 2 years, simultaneous radiotherapy at the first dose, the total dose of radiotherapy is 50.4Gy, completed in 28 divided doses, 1.8Gy each time, 5 times a week.
Intervention: Paclitaxel injection
Experimental group: carrelizumab in combination with concurrent chemoradiotherapy
Study drugs were administered intravenously on the first day of each cycle. Administered sequentially: carrelizumab, 200mg/time, paclitaxel, 50mg/m2, cisplatin, 25mg/m2, chemotherapy once a week, a total of 5 doses, carrelizumab every three weeks until PD or intolerable, up to 2 years, simultaneous radiotherapy at the first dose, the total dose of radiotherapy is 50.4Gy, completed in 28 divided doses, 1.8Gy each time, 5 times a week.
Intervention: Cisplatin
Experimental group: carrelizumab in combination with concurrent chemoradiotherapy
Study drugs were administered intravenously on the first day of each cycle. Administered sequentially: carrelizumab, 200mg/time, paclitaxel, 50mg/m2, cisplatin, 25mg/m2, chemotherapy once a week, a total of 5 doses, carrelizumab every three weeks until PD or intolerable, up to 2 years, simultaneous radiotherapy at the first dose, the total dose of radiotherapy is 50.4Gy, completed in 28 divided doses, 1.8Gy each time, 5 times a week.
Intervention: Concurrent chemoradiotherapy
Control group: placebo-resistant in combination with chemoradiotherapy
Placebo: 200 mg intravenously given with Q3W until PD or intolerable, carrelizumab/placebo for up to 2 years. Paclitaxel: 50mg/m2, iv, D1, 8, 15, 22, 29, once a week, a total of 5 times. cisplatin: 25mg/m2,iv, D1, 8, 15, 22, 29, once a week, a total of 5 doses. Radiotherapy: total dose of 50.4 Gy, completed in 28 divided doses of 1.8 Gy each time, 5 times a week.
Intervention: Paclitaxel injection
Control group: placebo-resistant in combination with chemoradiotherapy
Placebo: 200 mg intravenously given with Q3W until PD or intolerable, carrelizumab/placebo for up to 2 years. Paclitaxel: 50mg/m2, iv, D1, 8, 15, 22, 29, once a week, a total of 5 times. cisplatin: 25mg/m2,iv, D1, 8, 15, 22, 29, once a week, a total of 5 doses. Radiotherapy: total dose of 50.4 Gy, completed in 28 divided doses of 1.8 Gy each time, 5 times a week.
Intervention: Cisplatin
Control group: placebo-resistant in combination with chemoradiotherapy
Placebo: 200 mg intravenously given with Q3W until PD or intolerable, carrelizumab/placebo for up to 2 years. Paclitaxel: 50mg/m2, iv, D1, 8, 15, 22, 29, once a week, a total of 5 times. cisplatin: 25mg/m2,iv, D1, 8, 15, 22, 29, once a week, a total of 5 doses. Radiotherapy: total dose of 50.4 Gy, completed in 28 divided doses of 1.8 Gy each time, 5 times a week.
Intervention: Concurrent chemoradiotherapy
Outcomes
Primary Outcomes
PFS evaluated by IRC
Time Frame: up to 2 years
IRC stands for Independent Review Committee Assessment，Progression-free disease as assessed by an independent review committee Progression-free survival refers to the time from randomization to the first occurrence of disease progression or death from any cause
Secondary Outcomes
- OS Overall Survival(up to 2 years)
- ORR(through study completion, an average of 18 month)
- Progression-free survival evaluated by Researchers(up to 2 years)