Anlotinib in Combination With Toripalimab and Chemotherapy for Neoadjuvant Treatment of Resectable Esophageal Squamous Cell Carcinoma: a Phase II Clinical Study
Overview
- Phase
- Phase 2
- Intervention
- Toripalimab
- Conditions
- Esophageal Carcinoma
- Sponsor
- Nanfang Hospital, Southern Medical University
- Enrollment
- 25
- Primary Endpoint
- Pathologic complete remission (PCR)
- Status
- Not yet recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
The purpose of this study is to explore the effectiveness and safety of the combination of Anlotinib, Toripalimab, and albumin-bound paclitaxel with cisplatin for neoadjuvant therapy in resectable esophageal squamous cell carcinoma. The study aims to improve the pathological complete response rate (pCR), R0 resection rate, and disease-free survival (DFS) in patients undergoing esophageal cancer surgery. The findings of this study will provide guidance and new options for the treatment of locally advanced esophageal cancer patients.
Detailed Description
Both anti-angiogenic therapy and immune checkpoint inhibitors have shown preliminary efficacy and safety data in the field of neoadjuvant therapy for esophageal cancer. However, there is currently no available data on the combination of immune checkpoint inhibitors, anti-angiogenic therapy, and chemotherapy in neoadjuvant therapy for esophageal cancer. Based on the favorable survival benefits of this combination in first-line and second-line treatments for multiple tumors, we aim to explore another neoadjuvant treatment approach - adding anti-angiogenic agents to immune checkpoint inhibitor-based neoadjuvant therapy, providing a new perioperative treatment strategy for esophageal cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age range: 18-70 years, both male and female.
- •Patients with histopathological diagnosis of esophageal squamous cell carcinoma confirmed by gastroscopy/ultrasound gastroscopy, and clinical diagnosis of cT2N1-2M0 or cT3N0-2M0, with TNM staging of stage II-III B.
- •Non-cervical esophageal cancer patients.
- •No prior systemic or local treatment for esophageal cancer, with at least one measurable lesion for imaging evaluation of neoadjuvant therapy according to RECIST 1.1 criteria.
- •ECOG PS (Eastern Cooperative Oncology Group Performance Status): 0-
- •Estimated survival period ≥12 months.
- •Subjects without significant dysfunction of major organs, with normal assessment of thyroid, lung, liver, kidney, and cardiac function.
- •Reproductive-age women must have taken reliable contraceptive measures or undergone pregnancy testing (serum or urine) within 7 days prior to enrollment, with negative results, and be willing to use appropriate contraception during the trial and for 8 weeks after the last administration of the investigational drug. For males, they must agree to use appropriate contraception during the trial and for 8 weeks after the last administration of the investigational drug, or have undergone surgical sterilization.
- •Subjects voluntarily participate in this study, sign an informed consent form, demonstrate good compliance, adhere to the planned schedule for regular clinical follow-up and necessary treatment, and cooperate in obtaining regular blood and tissue samples.
Exclusion Criteria
- •Patients who have had or currently have other malignant tumors within the past 1.5 years, except for cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors \[Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor invades lamina propria)\].
- •Patients with ulcerative esophageal squamous cell carcinoma.
- •Patients with esophageal fistula or tracheal fistula.
- •Patients allergic to anlotinib, toripalimab, or albumin-bound paclitaxel.
- •Patients with a history of immunodeficiency diseases, including HIV-positive patients or those with other acquired or congenital immunodeficiency diseases, or a history of organ transplantation.
- •Patients with severe and/or uncontrolled diseases are excluded from the study, including:
- •6.1 Patients with unsatisfactory blood pressure control (systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mmHg).
- •6.2 Patients with grade I or higher myocardial ischemia or myocardial infarction.
- •6.3 Patients with arrhythmia (including QT interval ≥480 ms) and grade I heart failure.
- •6.4 Patients with poorly controlled diabetes (fasting blood glucose \>10 mmol/L) or receiving high-dose glucocorticoid therapy.
Arms & Interventions
Neoadjuvant Anlotinib Combined With Toripalimab and Chemotherapy
Toripalimab+ Anlotinib+Albumin-bound paclitaxel+Cisplatin
Intervention: Toripalimab
Neoadjuvant Anlotinib Combined With Toripalimab and Chemotherapy
Toripalimab+ Anlotinib+Albumin-bound paclitaxel+Cisplatin
Intervention: Anlotinib hydrochloride
Neoadjuvant Anlotinib Combined With Toripalimab and Chemotherapy
Toripalimab+ Anlotinib+Albumin-bound paclitaxel+Cisplatin
Intervention: Albumin paclitaxel
Neoadjuvant Anlotinib Combined With Toripalimab and Chemotherapy
Toripalimab+ Anlotinib+Albumin-bound paclitaxel+Cisplatin
Intervention: Cisplatin
Outcomes
Primary Outcomes
Pathologic complete remission (PCR)
Time Frame: Immediately after the surgery
Primary tumor or lymph node surgery specimen pathological examination without residual tumor cell
Secondary Outcomes
- Objective response rate (ORR)(Up to 36 month)
- Disease-free survival (DFS)(3(5) years after last patient enrolled)
- R0 resection rate(Immediately after the surgery)
- Overall survival (OS)(Up to 36 month)
- Disease control rate (DCR)(Up to 36 month)
- Safety: AE(Up to 36 month)
- Change From Baseline in HRQoL Score Using EORTC Quality of Life Questionnaire-Oesophageal Module (QLQ-OES18)(Up to 36 month)