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Neoadjuvant Therapy of Anlotinib Combined With Toripalimab and Chemotherapy for Resectable Esophageal Carcinoma

Primary Purpose

Esophageal Carcinoma, Neoadjuvant Therapy

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Toripalimab
Anlotinib hydrochloride
Albumin paclitaxel
Cisplatin
Sponsored by
Nanfang Hospital, Southern Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Carcinoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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): 0-1. 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. 6.5 Patients with active or uncontrolled severe infections. 6.6 Patients with decompensated liver disease, active hepatitis B (HBV-DNA ≥10^4 copies/ml or 2000 IU/ml), or hepatitis C (positive for hepatitis C antibodies and HCV RNA) exceeding the lower limit of the analytical method. 6.7 Patients with hyperthyroidism or hypothyroidism. 6.8 Patients with active tuberculosis. Unresolved toxicities of grade 2 or higher, excluding alopecia, caused by any prior treatment. Individuals with multiple factors that affect oral medication administration, such as dysphagia, chronic diarrhea, and intestinal obstruction. Individuals with urine routine showing urinary protein ≥++, and confirmed 24-hour urine protein quantification >1.0 g. Individuals who underwent major surgical treatment, incisional biopsy, or significant traumatic injury within 28 days prior to randomization. Abnormal coagulation function: INR >1.5 or prothrombin time (PT) > ULN + 4 seconds or APTT > 1.5 ULN, with a bleeding tendency or receiving thrombolytic or anticoagulation therapy. Patients who experienced any bleeding or hemorrhagic events ≥ grade 3 CTCAE within 4 weeks prior to randomization, with unhealed wounds, ulcers, or fractures. Occurrence of arterial/venous thrombotic events within 6 months, such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis, and pulmonary embolism. Pregnant or lactating women. Presence of distant metastasis. Patients with significant bone marrow suppression. Patients with mental illness or a history of substance abuse with psychotropic drugs. Patients who participated in other drug clinical trials within 4 weeks. Patients with accompanying diseases that, in the investigator's judgment, pose a serious risk to patient safety or may affect the patient's completion of the study. Patients with inherited bleeding tendencies, coagulation disorders, potential invasion of major blood vessels, and other bleeding risks, who experienced clinically significant bleeding symptoms or had a clear bleeding tendency with gastrointestinal bleeding, bleeding gastric ulcers, baseline fecal occult blood ++ and above within 3 months prior to enrollment. Patients deemed unsuitable

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Neoadjuvant Anlotinib Combined With Toripalimab and Chemotherapy

    Arm Description

    Toripalimab+ Anlotinib+Albumin-bound paclitaxel+Cisplatin

    Outcomes

    Primary Outcome Measures

    Pathologic complete remission (PCR)
    Primary tumor or lymph node surgery specimen pathological examination without residual tumor cell

    Secondary Outcome Measures

    R0 resection rate
    Residual tumor rate
    Objective response rate (ORR)
    ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
    Disease control rate (DCR)
    DCR is defined as the percentage of participants in the analysis population who have a CR, PR or stable disease (SD) per RECIST 1.1.
    Disease-free survival (DFS)
    Survival without local or systemic recurrence
    Overall survival (OS)
    Overall survival is defined as the duration from date of enrollment to the date of death from any cause.
    Safety: AE
    Safety was defined as the Number of Participants With an Adverse Event
    Change From Baseline in HRQoL Score Using EORTC Quality of Life Questionnaire-Oesophageal Module (QLQ-OES18)
    The EORTC QLQ-OES18 is a disease-specific questionnaire to assess measurements specific to esophageal cancer. It contains 18 items and is based on four subscales-dysphagia, eating, reflux and pain. All items are scored using a four-point scale that offers these response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. A higher score indicates worse level of symptoms. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in HRQoL QLQ-OES18 score in participants will be presented.

    Full Information

    First Posted
    August 10, 2023
    Last Updated
    August 16, 2023
    Sponsor
    Nanfang Hospital, Southern Medical University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05996484
    Brief Title
    Neoadjuvant Therapy of Anlotinib Combined With Toripalimab and Chemotherapy for Resectable Esophageal Carcinoma
    Official Title
    Anlotinib in Combination With Toripalimab and Chemotherapy for Neoadjuvant Treatment of Resectable Esophageal Squamous Cell Carcinoma: a Phase II Clinical Study
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 2023 (Anticipated)
    Primary Completion Date
    November 2024 (Anticipated)
    Study Completion Date
    July 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Nanfang Hospital, Southern Medical University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Esophageal Carcinoma, Neoadjuvant Therapy

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    25 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Neoadjuvant Anlotinib Combined With Toripalimab and Chemotherapy
    Arm Type
    Experimental
    Arm Description
    Toripalimab+ Anlotinib+Albumin-bound paclitaxel+Cisplatin
    Intervention Type
    Drug
    Intervention Name(s)
    Toripalimab
    Other Intervention Name(s)
    JS001
    Intervention Description
    Toripalimab, 240mg, IV., D1, every 3 weeks, 4 cycles.
    Intervention Type
    Drug
    Intervention Name(s)
    Anlotinib hydrochloride
    Other Intervention Name(s)
    Anlotinib
    Intervention Description
    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, every 3 weeks, 4 cycles.
    Intervention Type
    Drug
    Intervention Name(s)
    Albumin paclitaxel
    Other Intervention Name(s)
    Paclitaxel For Injection (Albumin Bound)
    Intervention Description
    Albumin paclitaxel, 200-260 mg/m2, IV., D1, every 3 weeks, 4 cycles.
    Intervention Type
    Drug
    Intervention Name(s)
    Cisplatin
    Other Intervention Name(s)
    CDDP
    Intervention Description
    Cisplatin, 60-75 mg/m2, IV., D1, every 3 weeks, 4 cycles.
    Primary Outcome Measure Information:
    Title
    Pathologic complete remission (PCR)
    Description
    Primary tumor or lymph node surgery specimen pathological examination without residual tumor cell
    Time Frame
    Immediately after the surgery
    Secondary Outcome Measure Information:
    Title
    R0 resection rate
    Description
    Residual tumor rate
    Time Frame
    Immediately after the surgery
    Title
    Objective response rate (ORR)
    Description
    ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
    Time Frame
    Up to 36 month
    Title
    Disease control rate (DCR)
    Description
    DCR is defined as the percentage of participants in the analysis population who have a CR, PR or stable disease (SD) per RECIST 1.1.
    Time Frame
    Up to 36 month
    Title
    Disease-free survival (DFS)
    Description
    Survival without local or systemic recurrence
    Time Frame
    3(5) years after last patient enrolled
    Title
    Overall survival (OS)
    Description
    Overall survival is defined as the duration from date of enrollment to the date of death from any cause.
    Time Frame
    Up to 36 month
    Title
    Safety: AE
    Description
    Safety was defined as the Number of Participants With an Adverse Event
    Time Frame
    Up to 36 month
    Title
    Change From Baseline in HRQoL Score Using EORTC Quality of Life Questionnaire-Oesophageal Module (QLQ-OES18)
    Description
    The EORTC QLQ-OES18 is a disease-specific questionnaire to assess measurements specific to esophageal cancer. It contains 18 items and is based on four subscales-dysphagia, eating, reflux and pain. All items are scored using a four-point scale that offers these response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. A higher score indicates worse level of symptoms. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in HRQoL QLQ-OES18 score in participants will be presented.
    Time Frame
    Up to 36 month

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    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): 0-1. 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. 6.5 Patients with active or uncontrolled severe infections. 6.6 Patients with decompensated liver disease, active hepatitis B (HBV-DNA ≥10^4 copies/ml or 2000 IU/ml), or hepatitis C (positive for hepatitis C antibodies and HCV RNA) exceeding the lower limit of the analytical method. 6.7 Patients with hyperthyroidism or hypothyroidism. 6.8 Patients with active tuberculosis. Unresolved toxicities of grade 2 or higher, excluding alopecia, caused by any prior treatment. Individuals with multiple factors that affect oral medication administration, such as dysphagia, chronic diarrhea, and intestinal obstruction. Individuals with urine routine showing urinary protein ≥++, and confirmed 24-hour urine protein quantification >1.0 g. Individuals who underwent major surgical treatment, incisional biopsy, or significant traumatic injury within 28 days prior to randomization. Abnormal coagulation function: INR >1.5 or prothrombin time (PT) > ULN + 4 seconds or APTT > 1.5 ULN, with a bleeding tendency or receiving thrombolytic or anticoagulation therapy. Patients who experienced any bleeding or hemorrhagic events ≥ grade 3 CTCAE within 4 weeks prior to randomization, with unhealed wounds, ulcers, or fractures. Occurrence of arterial/venous thrombotic events within 6 months, such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis, and pulmonary embolism. Pregnant or lactating women. Presence of distant metastasis. Patients with significant bone marrow suppression. Patients with mental illness or a history of substance abuse with psychotropic drugs. Patients who participated in other drug clinical trials within 4 weeks. Patients with accompanying diseases that, in the investigator's judgment, pose a serious risk to patient safety or may affect the patient's completion of the study. Patients with inherited bleeding tendencies, coagulation disorders, potential invasion of major blood vessels, and other bleeding risks, who experienced clinically significant bleeding symptoms or had a clear bleeding tendency with gastrointestinal bleeding, bleeding gastric ulcers, baseline fecal occult blood ++ and above within 3 months prior to enrollment. Patients deemed unsuitable
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    di lu, M.D., PhD
    Phone
    13268379321
    Email
    david_lu1989@163.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    kaican cai, M.D., PhD
    Organizational Affiliation
    Nanfang Hospital, Southern Medical University
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    Neoadjuvant Therapy of Anlotinib Combined With Toripalimab and Chemotherapy for Resectable Esophageal Carcinoma

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