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Immunotherapy After Radiotherapy in Elderly ESCC (TREE)

Primary Purpose

Esophageal Squamous Cell Carcinoma by AJCC V8 Stage

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Radiotherapy
Toripalimab
Sponsored by
The Central Hospital of Lishui City
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Squamous Cell Carcinoma by AJCC V8 Stage focused on measuring Esophageal Squamous Cell Carcinoma, PD-1, Elderly, Radiotherapy

Eligibility Criteria

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

Inclusion Criteria: Age ≥75 years old, regardless of gender; Esophageal cancer confirmed by histology or cytology; Unresectable, unable to tolerate or refuse surgery and concurrent chemoradiotherapy; Unable to tolerate chemotherapy; There are at least one lesions measurable according to RECIST 1.1; Stage II-iva (AJCC 8 TNM classification) Endoscopic ultrasonography confirmed that esophageal lesions did not invade adjacent organs (T1-4a).; ECOG PS 0-1; Forced expiratory volume (FEV) >0.8 liter; Life expectancy of at least 12 weeks; Have not received any anti-tumor treatment for esophageal cancer in the past, including radiotherapy, chemotherapy, surgery, biotherapy,etc. Has sufficient organ function: (1) Blood routine: ANC≥1.5×109/L; PLT≥50×109/L; HGB≥90 g/L((No blood transfusion and blood products within 14 days, no use of G-CSF and other blood-stimulating factors to correct)) (2) Liver function: TBIL ≤ 1.5 × ULN,ALT、AST ≤2.5 × ULN, (3) Renal function: Cr≤1×ULN or crcl ≥50 ml/min (4) Adequate haemostasis laboratory data prior to randomization: INR or PT ≤1.5×ULN (If the subject was receiving anticoagulant therapy, as long as the PT was within the intended use range of anticoagulant drugs) (5) Myocardial enzymes were within the normal range. Patients voluntarily joined this study, signed informed consent and provided diagnosis and treatment data after cancer diagnosis before entering the group, good compliance, and cooperation with follow-up visits; Exclusion Criteria: Synchronous or metachronous second primary malignancy. Participants with basal cell carcinoma of the skin, or cervical cancer in situ that have undergone potentially curative therapy are not excluded from the study; with multifocal primary esophageal cancer; The pathological diagnosis was esophageal small cell carcinoma, adenocarcinoma, or mixed carcinoma. Esophageal squamous cell carcinoma with active bleeding within 2 months of the primary lesion; Patients whose imaging has shown that the tumor has invaded the important blood vessels or the investigator judges that the tumor is likely to invade the important blood vessels and cause fatal hemorrhage during the follow-up study The patient has any active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, glomerulonephritis, thyroiditis (patients with vitiligo or asthma has been completely relieved in childhood, and do not need any intervention during adulthood can be included; patients with type I diabetes with good insulin control can also be included; hypothyroidism caused by autoimmune thyroiditis requiring hormone replacement therapy can also be included) Clinically significant cardiac disease or impaired cardiac function, such as: MeanQT interval corrected for heart rate (QTc) ≥470 ms, Congestive heart failure requiring treatment (New York Heart Association [NYHA] grade > 2), left ventricular ejection fraction (LVEF) <50% as determined by Echocardiography. Active infection or fever of unknown origin > 38.5 ° C during screening or before the first dose (tumor-related fever, as judged by the investigator, was eligible); Current pneumonitis or interstitial lung disease or history of pneumonitis or interstitial lung disease. Has had congenital or acquired immunodeficiency, such as human immunodeficiency virus (HIV) infection, active hepatitis B (HBV-DNA ≥ 104 copies/ml) or hepatitis C (HCR-RNA was higher than the detection limit of the analytical method); Previous treatment with another PD-1, PD-L1; Known hypersensitivity to macromolecular protein preparations or to any anti-PD-1 antibody component;; Immunosuppressive drugs used within 7 days prior to the initial study treatment, excluding local glucocorticoids, or systemic glucocorticoids at physiological doses (i.e., no more than 10 mg/ day of prednisone or equivalent doses of other glucocorticoids); Systemic steroid doses of less than 10 mg of prednisone daily or its equivalent are allowed in patients receiving physiologic replacement steroid doses without autoimmune disease. if they had undergone major surgery patients must have fully recovered from surgery with no major ongoing safety issues before the experiment begins. Currently participating in an interventional clinical research treatment, or has received another investigational drug or used an investigational device within 4 weeks prior to the first administration of the drug. Live vaccine within 4 weeks prior to first dose (Cycle 1, Day 1); NOTE: Injectable inactivated viral vaccine against seasonal influenza is allowed; however, live attenuated influenza vaccine for intranasal administration is not allowed. The investigator considers it unsuitable for inclusion. Patients with uncontrollable seizures or loss of self-control due to mental illness. serious abnormal laboratory test results, family, or social factors, which may affect the safety of the subjects or the data collection.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Radiotherapy Sequential Toripalimab

    Arm Description

    Radiotherapy:Intensity-modulated radiotherapy (IMRT) Immunotherapy: Toripalimab

    Outcomes

    Primary Outcome Measures

    Progression-free survival (PFS)
    We aim to evaluate the progression-free survival (PFS) of elderly patients with unresectable esophageal squamous cell carcinoma who were unable to accept concurrent chemotherapy and received sequential treatment with Triptolide injection after radiotherapy alone.

    Secondary Outcome Measures

    Overall survival (OS)
    Overall survival (OS) is defined as the time from treatment to death, regardless of disease recurrence .
    Objective response rate (ORR)
    Objective response rate (ORR) is defined as the proportion of patients with a complete response(CR) or partial response(PR) to treatment according to RECIST v1.1.
    Duration of response (DOR)
    Duration of response (DOR) was determined from date of initial response to PD according to RECIST v1.1.
    Time to death or distant metastasis (TTDM)
    Time to death or distant metastasis (TTDM) according to RECIST v1.1.

    Full Information

    First Posted
    March 17, 2023
    Last Updated
    March 17, 2023
    Sponsor
    The Central Hospital of Lishui City
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05791136
    Brief Title
    Immunotherapy After Radiotherapy in Elderly ESCC
    Acronym
    TREE
    Official Title
    Toripalimab After Radiotherapy Alone in Elderly Esophageal Squamous Cell Carcinoma: A Prospective Phase II Clinical Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    April 2023 (Anticipated)
    Primary Completion Date
    April 30, 2024 (Anticipated)
    Study Completion Date
    June 30, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    The Central Hospital of Lishui City

    4. Oversight

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

    5. Study Description

    Brief Summary
    The incidence and mortality of esophageal squamous cell carcinoma are at the forefront in China.Most part of patients are elderly. Concurrent chemoradiotherapy is the standard treatment for unresectable locally advanced esophageal squamous cell carcinoma. Most elderly patients cannot tolerate concurrent chemotherapy because of complications and other reasons. Immunotherapy has definite efficacy and low toxicity in advanced esophageal squamous cell carcinoma, and the results combined with radiotherapy have also been preliminarily reported. Therefore, it is necessary to further explore the efficacy and safety of radiotherapy combined with immunotherapy in elderly patients with esophageal squamous cell carcinoma.
    Detailed Description
    This is a prospective, multicenter, single-arm, phase Ⅱ clinical study to evaluate the efficacy and safety of radiotherapy alone followed by sequential injection of Toripalimab in elderly patients with unresectable esophageal squamous cell carcinoma who could not accept concurrent chemotherapy.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Esophageal Squamous Cell Carcinoma by AJCC V8 Stage
    Keywords
    Esophageal Squamous Cell Carcinoma, PD-1, Elderly, Radiotherapy

    7. Study Design

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

    8. Arms, Groups, and Interventions

    Arm Title
    Radiotherapy Sequential Toripalimab
    Arm Type
    Experimental
    Arm Description
    Radiotherapy:Intensity-modulated radiotherapy (IMRT) Immunotherapy: Toripalimab
    Intervention Type
    Radiation
    Intervention Name(s)
    Radiotherapy
    Other Intervention Name(s)
    Intensity-modulated radiotherapy (IMRT)
    Intervention Description
    95% PGTV56-60Gy/28-30 fractions, 2Gy/1 fractions; 95% PTV50.4-54Gy/28-30 fractions, 1.8Gy/1 fractions; 5 days a week; 6 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    Toripalimab
    Other Intervention Name(s)
    Immunotherapy
    Intervention Description
    Toripalimab (200 mg, intravenously infused) will be administered as the maintenance treatment every 3 weeks within 4 weeks after the completion of radiotherapy for 1 years or until progression, intolerable toxicity, or physician/patient decision
    Primary Outcome Measure Information:
    Title
    Progression-free survival (PFS)
    Description
    We aim to evaluate the progression-free survival (PFS) of elderly patients with unresectable esophageal squamous cell carcinoma who were unable to accept concurrent chemotherapy and received sequential treatment with Triptolide injection after radiotherapy alone.
    Time Frame
    2 years
    Secondary Outcome Measure Information:
    Title
    Overall survival (OS)
    Description
    Overall survival (OS) is defined as the time from treatment to death, regardless of disease recurrence .
    Time Frame
    2 years
    Title
    Objective response rate (ORR)
    Description
    Objective response rate (ORR) is defined as the proportion of patients with a complete response(CR) or partial response(PR) to treatment according to RECIST v1.1.
    Time Frame
    2 years
    Title
    Duration of response (DOR)
    Description
    Duration of response (DOR) was determined from date of initial response to PD according to RECIST v1.1.
    Time Frame
    2 years
    Title
    Time to death or distant metastasis (TTDM)
    Description
    Time to death or distant metastasis (TTDM) according to RECIST v1.1.
    Time Frame
    2 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age ≥75 years old, regardless of gender; Esophageal cancer confirmed by histology or cytology; Unresectable, unable to tolerate or refuse surgery and concurrent chemoradiotherapy; Unable to tolerate chemotherapy; There are at least one lesions measurable according to RECIST 1.1; Stage II-iva (AJCC 8 TNM classification) Endoscopic ultrasonography confirmed that esophageal lesions did not invade adjacent organs (T1-4a).; ECOG PS 0-1; Forced expiratory volume (FEV) >0.8 liter; Life expectancy of at least 12 weeks; Have not received any anti-tumor treatment for esophageal cancer in the past, including radiotherapy, chemotherapy, surgery, biotherapy,etc. Has sufficient organ function: (1) Blood routine: ANC≥1.5×109/L; PLT≥50×109/L; HGB≥90 g/L((No blood transfusion and blood products within 14 days, no use of G-CSF and other blood-stimulating factors to correct)) (2) Liver function: TBIL ≤ 1.5 × ULN,ALT、AST ≤2.5 × ULN, (3) Renal function: Cr≤1×ULN or crcl ≥50 ml/min (4) Adequate haemostasis laboratory data prior to randomization: INR or PT ≤1.5×ULN (If the subject was receiving anticoagulant therapy, as long as the PT was within the intended use range of anticoagulant drugs) (5) Myocardial enzymes were within the normal range. Patients voluntarily joined this study, signed informed consent and provided diagnosis and treatment data after cancer diagnosis before entering the group, good compliance, and cooperation with follow-up visits; Exclusion Criteria: Synchronous or metachronous second primary malignancy. Participants with basal cell carcinoma of the skin, or cervical cancer in situ that have undergone potentially curative therapy are not excluded from the study; with multifocal primary esophageal cancer; The pathological diagnosis was esophageal small cell carcinoma, adenocarcinoma, or mixed carcinoma. Esophageal squamous cell carcinoma with active bleeding within 2 months of the primary lesion; Patients whose imaging has shown that the tumor has invaded the important blood vessels or the investigator judges that the tumor is likely to invade the important blood vessels and cause fatal hemorrhage during the follow-up study The patient has any active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, glomerulonephritis, thyroiditis (patients with vitiligo or asthma has been completely relieved in childhood, and do not need any intervention during adulthood can be included; patients with type I diabetes with good insulin control can also be included; hypothyroidism caused by autoimmune thyroiditis requiring hormone replacement therapy can also be included) Clinically significant cardiac disease or impaired cardiac function, such as: MeanQT interval corrected for heart rate (QTc) ≥470 ms, Congestive heart failure requiring treatment (New York Heart Association [NYHA] grade > 2), left ventricular ejection fraction (LVEF) <50% as determined by Echocardiography. Active infection or fever of unknown origin > 38.5 ° C during screening or before the first dose (tumor-related fever, as judged by the investigator, was eligible); Current pneumonitis or interstitial lung disease or history of pneumonitis or interstitial lung disease. Has had congenital or acquired immunodeficiency, such as human immunodeficiency virus (HIV) infection, active hepatitis B (HBV-DNA ≥ 104 copies/ml) or hepatitis C (HCR-RNA was higher than the detection limit of the analytical method); Previous treatment with another PD-1, PD-L1; Known hypersensitivity to macromolecular protein preparations or to any anti-PD-1 antibody component;; Immunosuppressive drugs used within 7 days prior to the initial study treatment, excluding local glucocorticoids, or systemic glucocorticoids at physiological doses (i.e., no more than 10 mg/ day of prednisone or equivalent doses of other glucocorticoids); Systemic steroid doses of less than 10 mg of prednisone daily or its equivalent are allowed in patients receiving physiologic replacement steroid doses without autoimmune disease. if they had undergone major surgery patients must have fully recovered from surgery with no major ongoing safety issues before the experiment begins. Currently participating in an interventional clinical research treatment, or has received another investigational drug or used an investigational device within 4 weeks prior to the first administration of the drug. Live vaccine within 4 weeks prior to first dose (Cycle 1, Day 1); NOTE: Injectable inactivated viral vaccine against seasonal influenza is allowed; however, live attenuated influenza vaccine for intranasal administration is not allowed. The investigator considers it unsuitable for inclusion. Patients with uncontrollable seizures or loss of self-control due to mental illness. serious abnormal laboratory test results, family, or social factors, which may affect the safety of the subjects or the data collection.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Zhifeng Tian, M.D
    Phone
    0578-2285350
    Email
    tzf419@hotmail.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Wencai Li, M.D
    Phone
    0578-2285250
    Email
    liwencai2021@163.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Zhifeng Tian, M.D
    Organizational Affiliation
    Lishui Municipal Central Hospital,Zhejiang,China
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    participant number,age,gender

    Learn more about this trial

    Immunotherapy After Radiotherapy in Elderly ESCC

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