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SBRT Combined With AK104 to Treatment Relapsed or Metastatic ESCC

Primary Purpose

Recurrent or Metastatic Esophageal Squamous Cell Carcinoma

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
SBRT
Cadonilimab
Sponsored by
The First People's Hospital of Changzhou
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent or Metastatic Esophageal Squamous Cell Carcinoma focused on measuring SBRT, AK104

Eligibility Criteria

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

Inclusion Criteria: 1. age ≥ 18 years. 2. patients enrolled must be eligible for PD-1 treatment-naïve patients with recurrent or metastatic advanced esophageal squamous carcinoma with definite measurable recurrent or metastatic lesions. 3. have at least 2 or more clearly measurable lesions (maximum diameter of lesions≥1 cm and shortest diameter of ≥1.5 cm of lymph nodes according to RECIST v1.1), at least one of which is feasible for radiation therapy). 4. no congestive heart failure, unstable angina, or unstable arrhythmia within the last 6 months. 5. patient activity status score of 0-3 on the Eastern Cooperative Oncology Group (ECOG) scale with a life expectancy assessment of ≥ 3 months. 6. no previous serious abnormalities of hematopoietic, cardiac, pulmonary, hepatic, or renal function and immunodeficiency. 7. absolute T-lymphocyte values ≥ 0.5 times the lower limit of normal and neutrophils ≥ 2.0 × 109/L; AST and ALT ≤ 3.0 times the upper limit of normal (≤ 5.0 times the upper limit of normal for hepatocellular carcinoma/metastatic liver cancer); and creatinine ≤ 3.0 times the upper limit of normal, 1 week before enrollment. 8. patients must have the ability to understand and voluntarily sign the informed consent form. Exclusion Criteria: 1. pregnant gestational or lactating women. 2. those with a history of other malignant diseases in the last 5 years. 3. persons with a history of uncontrolled epilepsy, central nervous system disease, or psychiatric disorder whose clinical severity, as judged by the investigator, may prevent signing an informed consent form or affect patient compliance with medication. 4. clinically significant (i.e., active) heart disease such as symptomatic coronary artery disease, New York Heart Association (NYHA) class II or worse congestive heart failure or severe arrhythmias requiring pharmacologic intervention, or a history of myocardial infarction within the last 12 months. 5. organ transplantation requiring immunosuppressive therapy. 6. Significant active infection or, in the judgment of the investigator, significant hematologic, renal, metabolic, gastrointestinal, endocrine dysfunction or metabolic disorder, or other serious uncontrolled concomitant disease. 7. hypersensitivity to any investigational drug component. 8. have a history of immunodeficiency, including testing positive for HIV or having other acquired or congenital immunodeficiency diseases, or a history of organ transplantation, or other immune-related diseases requiring long-term oral hormone therapy. 9. those who are undergoing acute or chronic TB infection (patients with positive T-spot test and suspicious TB foci on chest radiograph). 10. other conditions that the investigator considers unsuitable for enrollment.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    SBRT combined with PD-1/CTLA-4 dual antibody

    Arm Description

    Outcomes

    Primary Outcome Measures

    ORR
    objective response rate

    Secondary Outcome Measures

    PFS
    progression-free surviva
    OS
    Overall survival
    Treatment Related Severe Adverse Effects
    Number of participants with treatment-related severe adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0

    Full Information

    First Posted
    February 8, 2023
    Last Updated
    February 8, 2023
    Sponsor
    The First People's Hospital of Changzhou
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05732662
    Brief Title
    SBRT Combined With AK104 to Treatment Relapsed or Metastatic ESCC
    Official Title
    SBRT Combined With PD-1/CTLA-4 Dual Antibody to Overcome Anti-PD-1 Resistant in Relapsed or Metastatic Esophageal Squamous Cell Carcinoma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    April 2023 (Anticipated)
    Primary Completion Date
    December 2025 (Anticipated)
    Study Completion Date
    December 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    The First People's Hospital of Changzhou

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No

    5. Study Description

    Brief Summary
    The entire treatment process is divided into two phases: Phase I SBRT combined with PD-1/CTLA-4 bispecific antibody (AK104) and Phase II AK104 single-agent maintenance therapy.
    Detailed Description
    Phase I SBRT combined with AK104 treatment Target area and dose of SBRT: Select a relapsed or metastatic lymph node or lesion that has little effect on surrounding normal tissues and has not been irradiated before, and then perform radiation therapy with a total dose of 24-50Gy/8-12.5Gy/3-4f per lesion (the specific target area and dose range will be decided by the treating physician). AK104 is administered within one week after SBRT, and the regimen for AK104 is 10 mg/kg as a single dose. If multiple target lesions are treated with SBRT, multiple cycles of 21 days each are possible. When patients are treated with multiple courses of radiotherapy, it is difficult to ensure the accuracy of the overlapping doses of the re-course of radiotherapy, and the cumulative dose of organs at risk (OAR) is evaluated using the deformable image registration (DIR) technique. Phase II AK104 monotherapy maintenance phase Monotherapy maintenance with AK104 10 mg/kg every 21 days until progression, up to one year if no progression. Patients were enrolled in Phase I and Phase II for a minimum of three cycles. In addition, 10 mL of peripheral blood was drawn from patients before each cycle of treatment and analyzed by flow cytometry for lymphocyte subpopulation. And the changes of HMGB1 and cytokines IL-8, IL-6, IL-12, IFN-α, IFN-β, IL-2, IL-4, IL-5, INF-γ, TNF-α, IL-10, TGF-β were detected by ELISA test. By testing the above indicators, they are used to respond to the immune status after treatment as well as to screen for valid indicators that can be used to assess efficacy. Throughout the study period, the assessment should be performed as much as possible according to the imaging assessment plan time points specified in the protocol. Tumor imaging assessments will be performed every 6 weeks during the first phase of treatment and every 9 weeks during the second phase of treatment. This project used velosity software to perform clinical tumor imaging assessment according to RECIST 1.1 criteria and irRECIST and iRECIST criteria assessment every 6 weeks; NCI-CTCAE 5.0 was used for safety assessment and adverse events were recorded throughout the study until 30 days after the end of treatment. After the end of treatment, all subjects will be followed for survival every 3 months until death, loss to follow-up, withdrawal of knowledge, or the sponsor's decision to terminate the study.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Recurrent or Metastatic Esophageal Squamous Cell Carcinoma
    Keywords
    SBRT, AK104

    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
    SBRT combined with PD-1/CTLA-4 dual antibody
    Arm Type
    Experimental
    Intervention Type
    Radiation
    Intervention Name(s)
    SBRT
    Intervention Description
    24-50Gy/8-12.5Gy/3-4f
    Intervention Type
    Drug
    Intervention Name(s)
    Cadonilimab
    Intervention Description
    10 mg/kg,q3w
    Primary Outcome Measure Information:
    Title
    ORR
    Description
    objective response rate
    Time Frame
    Up to 3 years
    Secondary Outcome Measure Information:
    Title
    PFS
    Description
    progression-free surviva
    Time Frame
    Up to 3 years
    Title
    OS
    Description
    Overall survival
    Time Frame
    Up to 3 years
    Title
    Treatment Related Severe Adverse Effects
    Description
    Number of participants with treatment-related severe adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
    Time Frame
    Up to 3 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: 1. age ≥ 18 years. 2. patients enrolled must be eligible for PD-1 treatment-naïve patients with recurrent or metastatic advanced esophageal squamous carcinoma with definite measurable recurrent or metastatic lesions. 3. have at least 2 or more clearly measurable lesions (maximum diameter of lesions≥1 cm and shortest diameter of ≥1.5 cm of lymph nodes according to RECIST v1.1), at least one of which is feasible for radiation therapy). 4. no congestive heart failure, unstable angina, or unstable arrhythmia within the last 6 months. 5. patient activity status score of 0-3 on the Eastern Cooperative Oncology Group (ECOG) scale with a life expectancy assessment of ≥ 3 months. 6. no previous serious abnormalities of hematopoietic, cardiac, pulmonary, hepatic, or renal function and immunodeficiency. 7. absolute T-lymphocyte values ≥ 0.5 times the lower limit of normal and neutrophils ≥ 2.0 × 109/L; AST and ALT ≤ 3.0 times the upper limit of normal (≤ 5.0 times the upper limit of normal for hepatocellular carcinoma/metastatic liver cancer); and creatinine ≤ 3.0 times the upper limit of normal, 1 week before enrollment. 8. patients must have the ability to understand and voluntarily sign the informed consent form. Exclusion Criteria: 1. pregnant gestational or lactating women. 2. those with a history of other malignant diseases in the last 5 years. 3. persons with a history of uncontrolled epilepsy, central nervous system disease, or psychiatric disorder whose clinical severity, as judged by the investigator, may prevent signing an informed consent form or affect patient compliance with medication. 4. clinically significant (i.e., active) heart disease such as symptomatic coronary artery disease, New York Heart Association (NYHA) class II or worse congestive heart failure or severe arrhythmias requiring pharmacologic intervention, or a history of myocardial infarction within the last 12 months. 5. organ transplantation requiring immunosuppressive therapy. 6. Significant active infection or, in the judgment of the investigator, significant hematologic, renal, metabolic, gastrointestinal, endocrine dysfunction or metabolic disorder, or other serious uncontrolled concomitant disease. 7. hypersensitivity to any investigational drug component. 8. have a history of immunodeficiency, including testing positive for HIV or having other acquired or congenital immunodeficiency diseases, or a history of organ transplantation, or other immune-related diseases requiring long-term oral hormone therapy. 9. those who are undergoing acute or chronic TB infection (patients with positive T-spot test and suspicious TB foci on chest radiograph). 10. other conditions that the investigator considers unsuitable for enrollment.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Wendong Gu, Doctor
    Phone
    13861220022
    Ext
    0519-68871162
    Email
    guwendong1415@czfph.com

    12. IPD Sharing Statement

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    SBRT Combined With AK104 to Treatment Relapsed or Metastatic ESCC

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