Anlotinib Hydrochloride Capsules Combined With TQB2450 Injection in Esophageal Squamous Cell Carcinoma Patients

Study Overview
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Brief Summary
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This is an Open, Single Arm, Exploratory and Phase II Clinical Trial of Anlotinib Hydrochloride Capsules Combined With TQB2450 Injection in Esophageal Squamous Cell Carcinoma (ESCC) Patients as Postoperative Adjuvant Therapy. In order to observe and evaluate the efficacy and safety of Anlotinib Hydrochloride Capsules combined with TQB2450 Injection in treatment of patients with ESCC. The primary endpoint is disease free survival (DFS).

Detailed Description
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This is an Open, Single Arm, Exploratory and Phase II Clinical Trial of Anlotinib Hydrochloride Capsules Combined With TQB2450 Injection in Esophageal Squamous Cell Carcinoma (ESCC) Patients as Postoperative Adjuvant Therapy. In order to observe and evaluate the efficacy and safety of Anlotinib Hydrochloride Capsules combined with TQB2450 Injection in treatment of patients with Esophageal Squamous Cell Carcinoma (ESCC). Primary Efficacy Endpoint: Disease Free Survival (DFS) (According to RECIST Version 1.1), Secondary Efficacy Endpoints:1-year DFS rate, 3-year DFS rate, 1-year Overall Survival (OS) rate, 3-year OS rate, and Safety. Safety and tolerance will be evaluated by incidence, severity and outcomes of AEs and categorized by severity in accordance with the NCI CTC AE Version 5.0.

Official Title
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An Open, Single Arm, Multicenter, Exploratory Phase II Clinical Trial of Anlotinib Hydrochloride Capsules Combined With TQB2450 Injection in Esophageal Squamous Cell Carcinoma Patients as Postoperative Adjuvant Therapy

Conditions
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Esophageal Squamous Cell Carcinoma, Esophageal Neoplasms, Esophageal Diseases, Gastrointestinal Neoplasms, Gastrointestinal Diseases, Digestive System Neoplasms, Digestive System Diseases, Neoplasms by Site, Neoplasms by Histologic Type, Neoplasms, Squamous Cell, Carcinoma, Squamous Cell

Intervention / Treatment
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* Drug: Anlotinib hydrochloride
* Drug: TQB2450


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects volunteered to join the study, signed informed consent, good compliance, with follow-up. ≥ 18 years old. ECOG performance status of 0-1 Patients with esophageal squamous cell carcinoma pathologically diagnosed as T1-2N1-3M0 or T3-4NanyM0. Patients received radical (R0) resection of squamous cell carcinoma with no recurrence in imaging examination within 6-12 weeks after surgery, and need adjuvant therapy assessed by the researchers. Laboratory tests must be met: Neutrophils count =/> 1.5 x 109/L, platelets count =/> 75 x 109/L, Hb =/> 90 g/L, WBC =/> 3 x 109/L. total bilirubin =/< 1.5 x ULN, ALT and AST =/< 2.5 x ULN. Creatinine =/< 1.5 x ULN. APTT, INR, PT =/< 1.5 x ULN. TSH =/< ULN. Myocardial enzymes in the normal range. LVEF =/> 50%. Exclusion Criteria: Patients received other antitumor adjuvant therapy after surgical resection. Concurrent malignancy (except cured basal cell carcinoma of the skin). Patients was diagnosed cervical esophageal carcinoma. Patients who have received prior targeted therapy (anti-VEGF/VEGFR) or immunity therapy (anti-PD-1/PD-L1/CTLA-4). Patients who are allergic to other monoclonal antibodies. Patients with a history of immunodeficiency (or active autoimmue disease), or other acquired congenital immunodeficiency diseases. Immunosuppressant, systemic, or absorbable local hormone therapy (> 10mg/ day of prednisone or other equivalent hormone) is required for immunosuppression and continued within 2 weeks of initial administration. Patients with multiple factors affecting oral administration. Uncontrolled pleural effusion, pericardial effusion or ascites that requires repeated drainage. With bleeding tendency. Patients with any bleeding or bleeding event CTC AE grade 3 in the 4 weeks prior to initial administration. The presence of digestive diseases or active bleeding of unresected tumors, or other conditions that the investigator determined which could lead to gastrointestinal bleeding or perforation. Active or untreated CNS metastases as determined by CT or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments. Patients with hypertension who could not be well controlled by antihypertensive drugs (systolic blood pressure > 160 mmHg, diastolic blood pressure > 100 mmHg). Patients with myocardial infarction, myocardial ischemia, arrhythmias with poor control (including QTC interval male > 450 ms, female> 470 ms) and cardiac insufficiency of grade II according to NYHA standard. Active or uncontrolled severe infection (≥ CTC AE Grade 2 infection). HIV test positive. Proteinuria =/>2+ and confirmed 24-hour urinary protein quantification > 1.0 g. Vaccination with prophylactic or attenuated vaccine within 4 weeks prior to initial administration. According to the investigators' judgment, there are factors that endanger patient or prevent patients from completing the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anlotinib<br>Patients in the study group will receive the following treatment: 21 days as a treatment cycle, Anlotinib 12 mg/day, Orally (D1-D14); TQB 2450 1200 mg, iv (D1). If anlotinib is not tolerated, the dose can be reduced to 10mg or 8mg, until un-tolerable toxicity again. | Drug: Anlotinib hydrochloride<br>* Anlotinib Hydrochloride is a capsule in the form of 8 mg ,10 mg and 12 mg, orally, once daily, 2 weeks on/1 week off.<br>Drug: TQB2450<br>* TQB2450 is an injection in the form of 600 mg; 1200 mg, iv, D1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DFS | Disease Free Survival | DFS was defined as the time from the day patients received first dose of treatment regimen until the date of first documented recurrence or death from any cause, whichever come first, assessed up to 96 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year DFS rate | One year Disease Free Survival rate | 1-year DFS rate was disease-free survival rate at the time since patients received first dose of treatment regimen for one year. | 
| 3-year DFS rate | Three year Disease Free Survival rate | 3-year DFS rate was disease-free survival rate at the time since patients received first dose of treatment regimen for 3 years. | 
| 1-year OS rate | One year Overall Survival rate | 1-year OS rate was overall survival rate at the time since patients received first dose of treatment regimen for one year. | 
| 3-year OS rate | Three year Overall Survival rate | 3-year OS rate was overall survival rate at the time since patients received first dose of treatment regimen for 3 years. |