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Envollizumab Combined With Fruquintinib and SOX Versus SOX for Conversion Therapy in Advanced Gastric Cancer

Primary Purpose

Gastric Cancer

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Envolimab
Fruquintinib
Oxaliplatin
Tegafur
Sponsored by
Fujian Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric Cancer

Eligibility Criteria

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

Inclusion Criteria: Age: 18-75 years of age; Pathological (including histological or cytological) confirmation of gastric adenocarcinoma; Before surgery, CT/MRI, PET-CT, if necessary, laparoscopic exploration to determine the clinical stage of T4bN0M0 and TanyN2-3M0, and determined by researchers that the local advanced patients can not be resectable; At least one measurable detected by CT examination in accordance with the RECIST1.1 ECOG#Eastern Cooperative Oncology Group#PS#Performance Status#:0-1 scores; The expected survival time is more than 3 months The main organ function is normal, which should meet the following criteria: #1#blood routine examination standards should be met#no blood transfusion within 14 days# a.HB≥ 100g/L b. WBC≥3×109/L c. ANC≥1.5×109/L d. PLT≥100×109/L #2#biochemical examination shall comply with the following criteria# BIL#1.5 normal upper limit ULN ALT and AST#2.5 ULN Cr≤1 ULN#CCR#creatinine clearance rate##60ml/min(Cockcroft Gault formula) Women of childbearing age must have a pregnancy test in 7 days before entering the group (in serum), and the results were negative, and willing to use appropriate contraception during the study period and the last 8 weeks after giving drug test; men should have the surgical sterilization, or adopt the appropriate contraceptive methods during the test and the last 8 weeks after giving drug test# No other clinical studies were conducted before and during the treatment Participants is willing to participate in this study, sign the informed consent, have good compliance, cooperate with follow-up Exclusion Criteria: Imaging or intraoperative exploration found patients with peritoneum, liver, lung and other distant metastases Patients with allergies or suspected allergies to study drugs or similar drugs Confirmed HER-2 positive patients Other malignancies in the past 5 years, except basal cell or squamous cell carcinoma of the skin after radical surgery, or carcinoma in situ of the cervix Live vaccine was administered within 4 weeks prior to enrolling or possibly during the study period Had an active autoimmune disease or a history of autoimmune disease within 4 weeks prior to enrollment Past recipients of allogeneic bone marrow transplants or organ transplants Patient has any current disease or condition that affects drug absorption, or the patient is unable to take the drug orally The blood pressure of patients with hypertension cannot be reduced to the normal range by the one antihypertensive drugs (systolic pressure ≥150 mmHg, diastolic pressure ≥100 mmHg) or hard to controled by two or more antihypertensive drugs Patients are positive of urine protein (urine protein detection 2+ or above, or 24 hours urine protein quantitative >1.0g) The patient currently has gastrointestinal diseases such as active gastric and duodenal ulcers, ulcerative colitis, or active bleeding from unresectosed tumors, or other conditions determined by researchers that may cause gastrointestinal bleeding or perforation Patients with significant evidence or history of bleeding tendency within 3 months prior to enrollment (bleeding within 3 months >30 mL, hematemesis, black stool, blood in stool), hemoptysis (within 4 weeks >5 mL fresh blood) or a thromboembolic event (including stroke and/or transient ischemic attack) within 12 months Cardiovascular disease of significant clinical significance, including but not limited to acute myocardial infarction, severe/unstable angina, or coronary artery bypass grafting within 6 months prior to enrollment; New York Heart Association (NYHA) Grades for Congestive Heart Failure more than class II ; Ventricular arrhythmias requiring medical treatment; An electrocardiogram (ECG) showed a QT c interval ≥480 milliseconds Active or uncontrolled severe infection (≥CTCAE grade 2 infection) A history of human immunodeficiency virus (HIV) infection or clinically significant liver disease, including viral hepatitis [active HBV infection must be ruled out as a known carrier of hepatitis B virus (HBV), i.e. positive HBV DNA (>1×104 copies /mL or >2000 IU/ml); known hepatitis C virus infection (HCV) and HCV RNA positive (>1×103 copies /mL), or other hepatitis, cirrhosis] The researchers consider those who were not suitable for inclusion

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Envolimab + fruquinitinib +SOX regimen

    SOX regimen

    Arm Description

    Outcomes

    Primary Outcome Measures

    Surgical conversion rate
    Defined as the proportion of patients who have undergone surgical resection after multidisciplinary assessment after completing 4-6 cycles of conversion therapy

    Secondary Outcome Measures

    Pathological complete response (pCR)
    Measured as the proportion of participants with a pathological complete response at the time of definitive surgery.
    Median disease free survival (DFS) time
    The time from opreation to the time when only 50% of the individuals had no relapse or tumor progression
    1-year DFS rate
    3-year DFS rate
    Objective response rate (ORR)
    Defined as the percentage of the participants in the analysis population who had a confirmed patial response and complete reponse according to RECIST 1.1 based on investigator assessment
    Major pathological response rate (MPR)
    The proportion of participants with a major pathological response (mPR) at the time of definitive surgery.
    R0 resection rate
    Defined as no residue under the microscope after resection
    Median survival time
    The time from enrollment to the time when only 50% of the individuals alive
    Adverse event (AEs)
    Toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. The number of Participants with adverse events will be recorded at each treatment visit.
    Quality of life (QOL)
    The quality of life of patients during treatment is eveluated by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 (V3.0)

    Full Information

    First Posted
    May 27, 2023
    Last Updated
    August 23, 2023
    Sponsor
    Fujian Medical University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05914610
    Brief Title
    Envollizumab Combined With Fruquintinib and SOX Versus SOX for Conversion Therapy in Advanced Gastric Cancer
    Official Title
    Envollizumab Combined With Fruquintinib and SOX Versus SOX for Conversion Therapy in Her-2 Negative Unresectable Locally Advanced Gastric Cancer: a National Multicenter Randomized Controlled Study
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 1, 2023 (Anticipated)
    Primary Completion Date
    July 30, 2025 (Anticipated)
    Study Completion Date
    July 30, 2028 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Fujian 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
    To investigate the clinical efficacy and safety of envollizumab combined with fruquintinib and SOX versus SOX in conversion therapy for patients with Her-2 negative, unresectable locally advanced gastric cancer.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Gastric Cancer

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    100 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Envolimab + fruquinitinib +SOX regimen
    Arm Type
    Experimental
    Arm Title
    SOX regimen
    Arm Type
    Active Comparator
    Intervention Type
    Drug
    Intervention Name(s)
    Envolimab
    Intervention Description
    Envolizumab 300mg, D1, ih, Q3W 4-6cycles
    Intervention Type
    Drug
    Intervention Name(s)
    Fruquintinib
    Intervention Description
    Fruquinitinib 3mg/d, QD, PO, D1-D14, Q3W 4-6cycles
    Intervention Type
    Drug
    Intervention Name(s)
    Oxaliplatin
    Intervention Description
    Oxaliplatin 130 mg/m2, ivgtt 0-2h, D1, Q3W 4-6cycles
    Intervention Type
    Drug
    Intervention Name(s)
    Tegafur
    Intervention Description
    Tegafur was calculated according to body surface area , P.O., bid, d1-d14#And the dosage according body surface area:<1.25m2, 40mg every time;1.25-1.5m2,50mg every time; >1.5m2, 60mg every time Q3W 4-6cycles
    Primary Outcome Measure Information:
    Title
    Surgical conversion rate
    Description
    Defined as the proportion of patients who have undergone surgical resection after multidisciplinary assessment after completing 4-6 cycles of conversion therapy
    Time Frame
    2-3 months
    Secondary Outcome Measure Information:
    Title
    Pathological complete response (pCR)
    Description
    Measured as the proportion of participants with a pathological complete response at the time of definitive surgery.
    Time Frame
    4 months
    Title
    Median disease free survival (DFS) time
    Description
    The time from opreation to the time when only 50% of the individuals had no relapse or tumor progression
    Time Frame
    3 years
    Title
    1-year DFS rate
    Time Frame
    1 year
    Title
    3-year DFS rate
    Time Frame
    3 years
    Title
    Objective response rate (ORR)
    Description
    Defined as the percentage of the participants in the analysis population who had a confirmed patial response and complete reponse according to RECIST 1.1 based on investigator assessment
    Time Frame
    4 months
    Title
    Major pathological response rate (MPR)
    Description
    The proportion of participants with a major pathological response (mPR) at the time of definitive surgery.
    Time Frame
    4 months
    Title
    R0 resection rate
    Description
    Defined as no residue under the microscope after resection
    Time Frame
    2-3 month
    Title
    Median survival time
    Description
    The time from enrollment to the time when only 50% of the individuals alive
    Time Frame
    3 years
    Title
    Adverse event (AEs)
    Description
    Toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. The number of Participants with adverse events will be recorded at each treatment visit.
    Time Frame
    2 years
    Title
    Quality of life (QOL)
    Description
    The quality of life of patients during treatment is eveluated by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 (V3.0)
    Time Frame
    2 years

    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: 18-75 years of age; Pathological (including histological or cytological) confirmation of gastric adenocarcinoma; Before surgery, CT/MRI, PET-CT, if necessary, laparoscopic exploration to determine the clinical stage of T4bN0M0 and TanyN2-3M0, and determined by researchers that the local advanced patients can not be resectable; At least one measurable detected by CT examination in accordance with the RECIST1.1 ECOG#Eastern Cooperative Oncology Group#PS#Performance Status#:0-1 scores; The expected survival time is more than 3 months The main organ function is normal, which should meet the following criteria: #1#blood routine examination standards should be met#no blood transfusion within 14 days# a.HB≥ 100g/L b. WBC≥3×109/L c. ANC≥1.5×109/L d. PLT≥100×109/L #2#biochemical examination shall comply with the following criteria# BIL#1.5 normal upper limit ULN ALT and AST#2.5 ULN Cr≤1 ULN#CCR#creatinine clearance rate##60ml/min(Cockcroft Gault formula) Women of childbearing age must have a pregnancy test in 7 days before entering the group (in serum), and the results were negative, and willing to use appropriate contraception during the study period and the last 8 weeks after giving drug test; men should have the surgical sterilization, or adopt the appropriate contraceptive methods during the test and the last 8 weeks after giving drug test# No other clinical studies were conducted before and during the treatment Participants is willing to participate in this study, sign the informed consent, have good compliance, cooperate with follow-up Exclusion Criteria: Imaging or intraoperative exploration found patients with peritoneum, liver, lung and other distant metastases Patients with allergies or suspected allergies to study drugs or similar drugs Confirmed HER-2 positive patients Other malignancies in the past 5 years, except basal cell or squamous cell carcinoma of the skin after radical surgery, or carcinoma in situ of the cervix Live vaccine was administered within 4 weeks prior to enrolling or possibly during the study period Had an active autoimmune disease or a history of autoimmune disease within 4 weeks prior to enrollment Past recipients of allogeneic bone marrow transplants or organ transplants Patient has any current disease or condition that affects drug absorption, or the patient is unable to take the drug orally The blood pressure of patients with hypertension cannot be reduced to the normal range by the one antihypertensive drugs (systolic pressure ≥150 mmHg, diastolic pressure ≥100 mmHg) or hard to controled by two or more antihypertensive drugs Patients are positive of urine protein (urine protein detection 2+ or above, or 24 hours urine protein quantitative >1.0g) The patient currently has gastrointestinal diseases such as active gastric and duodenal ulcers, ulcerative colitis, or active bleeding from unresectosed tumors, or other conditions determined by researchers that may cause gastrointestinal bleeding or perforation Patients with significant evidence or history of bleeding tendency within 3 months prior to enrollment (bleeding within 3 months >30 mL, hematemesis, black stool, blood in stool), hemoptysis (within 4 weeks >5 mL fresh blood) or a thromboembolic event (including stroke and/or transient ischemic attack) within 12 months Cardiovascular disease of significant clinical significance, including but not limited to acute myocardial infarction, severe/unstable angina, or coronary artery bypass grafting within 6 months prior to enrollment; New York Heart Association (NYHA) Grades for Congestive Heart Failure more than class II ; Ventricular arrhythmias requiring medical treatment; An electrocardiogram (ECG) showed a QT c interval ≥480 milliseconds Active or uncontrolled severe infection (≥CTCAE grade 2 infection) A history of human immunodeficiency virus (HIV) infection or clinically significant liver disease, including viral hepatitis [active HBV infection must be ruled out as a known carrier of hepatitis B virus (HBV), i.e. positive HBV DNA (>1×104 copies /mL or >2000 IU/ml); known hepatitis C virus infection (HCV) and HCV RNA positive (>1×103 copies /mL), or other hepatitis, cirrhosis] The researchers consider those who were not suitable for inclusion

    12. IPD Sharing Statement

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    Envollizumab Combined With Fruquintinib and SOX Versus SOX for Conversion Therapy in Advanced Gastric Cancer

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