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XELOX Combined With Fruquintinib and Sintilimab Regimen Conversion Therapy for Gastric Cancer/Gastroesophageal Junction Adenocarcinoma Only With Liver and/or Retroperitoneal Lymph Node Metastasis, a Prospective Single-arm, Multicenter Study

Primary Purpose

Gastric Cancer/Gastroesophageal Junction Adenocarcinoma

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
XELOX combined with Fruquintinib and Sintilimab
Sponsored by
Xiaofeng Chen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric Cancer/Gastroesophageal Junction Adenocarcinoma

Eligibility Criteria

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

Inclusion Criteria: Age: 18-75 years of age; Understand the steps and content, and written informed consent signed voluntarily; Is confirmed by histopathology and/or cytology her2-negative or HER2 status unknown late recurrence or stomach esophagus stomach/integration of adenocarcinoma; In this research to define transfer of oligonucleotides definition: the primary lesion and regional lymph node metastasis of process to determine the surgeon can be cut or boundary can be cut, only intrahepatic metastasis and distant metastasis (metastases number 5 or less, a single lesion or less 5 cm in diameter.) And or retroperitoneal lymph node metastasis (16a2,16b1,16a1,16b2 metastasis), no other distant metastasis; At least one measurable lesion according to RECIST 1.1 criteria; No previous treatment with VEGFR-targeted drugs and PD-1/PD-L1 monoclonal antibodies. Patients who had relapsed more than 6 months after the completion of postoperative adjuvant chemotherapy with platinum or paclitaxel or fluorouracil and had no grade 2 or higher toxicity were eligible for enrollment. ECOG PS score: 0-1; Expected survival time ≥3 months; The main viscera function is good, namely into groups of related within 14 days before check index meet the following requirements: (1) hemoglobin ≥80 g/L; (2) neutrophil count >1.5×109/L; (3) platelet count ≥80×109/L; (4) Total bilirubin ≤2.5×ULN (upper limit of normal); (5) serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤5×ULN; (6) the endogenous creatinine clearance or 60 ml/min (Cockcroft - Gault formula); (7) Echocardiography: left ventricular ejection fraction (LVEF)≥50%; (8) Thyroid function indexes: thyroid stimulating hormone (TSH) and free thyroxine (FT3/FT4) were in the normal range or only mildly abnormal, without related clinical symptoms; (9) A body weight of 40 kg or more, or a BMI > 18.5; Exclusion Criteria: Patients with other malignant tumors in the past or at the same time, but have been cured of early tumors, including basal cell carcinoma of the skin and carcinoma in situ of the cervix, stage I lung cancer, stage I colorectal cancer and other tumors that do not affect the patient's life in the short term according to the investigator's judgment can be excluded; Participated in other drug clinical trials within four weeks; Multiple factors affecting oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction); Patients with a history of bleeding and any bleeding events of CTCAE5.0 grade 3 or higher within 4 weeks before screening; Metastasis in other distant sites, including but not limited to lung metastasis, brain metastasis, bone metastasis, distant lymph node metastasis, and peritoneal metastasis; Patients with hypertension not well controlled by single antihypertensive medication (systolic blood pressure >140 mmHg, diastolic blood pressure >90 mmHg); Patients with a history of unstable angina; Newly diagnosed angina pectoris within 3 months before screening or myocardial infarction within 6 months before screening; Arrhythmias (including QTcF ≥450 ms in men and ≥470 ms in women) required long-term use of antiarrhythmic drugs and New York Heart Association (NYHA) grade ≥II cardiac dysfunction; Long-term unhealed wounds or incompletely healed fractures; Imaging shows that the tumor has invaded the important blood vessels or the investigator judges that the patient's tumor has a high possibility of invading the important blood vessels during the treatment and causing fatal hemorrhage; Abnormal coagulation function, with bleeding tendency (14 days before enrollment must meet: INR in the normal range without anticoagulant or clinically insignificant abnormality); Patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin, or their analogues; International standardization in prothrombin time ratio (INR) under the premise of 1.5 or less, allowing purpose to prevent the use of low-dose warfarin (1 mg orally, once per day) or low-dose aspirin (amount does not exceed 100 mg daily); Occurrence of arterial/venous thrombosis events within 6 months before screening, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis (except for venous thrombosis caused by venous catheterization due to previous chemotherapy and judged by investigators to be cured), and pulmonary embolism; Urine routine showed urine protein ≥++ and confirmed 24-hour urine protein quantitation >1.0 g; Previous use of immune-targeted therapy drugs; Have a history of immunodeficiency or other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation; Patients with infectious pneumonia, non-infectious pneumonia, interstitial pneumonia and other patients requiring corticosteroids; A history of severe chronic autoimmune diseases, such as systemic lupus erythematosus; He had a history of inflammatory bowel disease such as ulcerative enteritis, Crohn's disease, and a history of chronic diarrhea such as irritable bowel syndrome. A history of sarcoidosis or tuberculosis; Patients with a history of active hepatitis B or C, and HIV infection; Good control of severe autoimmune disease, such as dermatitis, arthritis, psoriasis, etc can be into the group. Patients with hepatitis B virus titer <1000copy/ml were eligible for enrollment. Patients with hypersensitivity to human or murine monoclonal antibodies; Have a history of psychotropic drug abuse and cannot quit or have mental disorders; Patients who do not follow the doctor's advice, do not follow the prescribed medication, or have incomplete data, which may affect the efficacy or safety judgment; Concomitant diseases that, in the judgment of the investigator, seriously compromise patient safety or interfere with patient completion of the study.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Experimental

    Arm Description

    XELOX combined with Fruquintinib and Sintilimab

    Outcomes

    Primary Outcome Measures

    Progression free survival (PFS)
    Time from randomization to disease progression or death from any cause

    Secondary Outcome Measures

    Overall survival (OS)
    Overall survival means any reason from patients into groups to the date of death
    Objective response rate (ORR)
    the proportion of patients with complete response or partial response, using RECIST v 1.1.
    Disease Control Rate (DCR)
    the proportion of patients with complete response, partial response or stable disease, using RECIST v 1.1.
    Duration of Response (DOR)
    Cancer for the first time that assessment for CR or PR to the first evaluation for PD or any cause the time of death.
    translational rate
    It refers to the proportion of all enrolled patients who underwent radical surgery/ablation therapy after medical treatment.
    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.

    Full Information

    First Posted
    October 10, 2023
    Last Updated
    October 17, 2023
    Sponsor
    Xiaofeng Chen
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06091423
    Brief Title
    XELOX Combined With Fruquintinib and Sintilimab Regimen Conversion Therapy for Gastric Cancer/Gastroesophageal Junction Adenocarcinoma Only With Liver and/or Retroperitoneal Lymph Node Metastasis, a Prospective Single-arm, Multicenter Study
    Official Title
    XELOX Combined With Fruquintinib and Sintilimab Regimen Conversion Therapy for Gastric Cancer/Gastroesophageal Junction Adenocarcinoma Only With Liver and/or Retroperitoneal Lymph Node Metastasis, a Prospective Single-arm, Multicenter Study ( FISSION Study )
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 25, 2023 (Anticipated)
    Primary Completion Date
    November 25, 2025 (Anticipated)
    Study Completion Date
    November 25, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    Xiaofeng Chen

    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
    Gastric cancer is the third leading cause of morbidity and mortality among malignant tumors in China, and less than 30% of patients can be cured by surgery. Liver metastasis, retroperitoneal lymph node metastasis and peritoneal metastasis are the most common metastatic sites of gastric cancer, which are also the important causes of death. Improve the conversion of oligonucleotides transfer patients resection rate, prolonged progression-free survival of these patients, is an important direction to improve survival of patients with advanced gastric cancer; This study was a prospective, single-arm, multi-center clinical study. We plan to treat patients with gastric cancer/gastroesophageal junction adenocarcinoma with liver and/or retroperitoneal lymph node metastasis only with XELOX regimen + fruquinitinib + sintilimab for 4-6 cycles before surgery/ablation conversion therapy to achieve tumor-free status as far as possible. To explore the value of conversion therapy in patients with intrahepatic oligometastasis of gastric cancer.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Gastric Cancer/Gastroesophageal Junction Adenocarcinoma

    7. Study Design

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

    8. Arms, Groups, and Interventions

    Arm Title
    Experimental
    Arm Type
    Experimental
    Arm Description
    XELOX combined with Fruquintinib and Sintilimab
    Intervention Type
    Drug
    Intervention Name(s)
    XELOX combined with Fruquintinib and Sintilimab
    Intervention Description
    XELOX:Capecitabine:800mg/m2, po, bid, d1-14。Oxaliplatin:130mg/m2,ivgtt 2-6h,d1,q3w; Fruquintinib: 5 mg/d,qd po,d1-14,q3w; Sintilimab: 200mg d1, q3w
    Primary Outcome Measure Information:
    Title
    Progression free survival (PFS)
    Description
    Time from randomization to disease progression or death from any cause
    Time Frame
    from randomization up to progressive disease or EOT due to any cause, assessed up to 2 year]
    Secondary Outcome Measure Information:
    Title
    Overall survival (OS)
    Description
    Overall survival means any reason from patients into groups to the date of death
    Time Frame
    from randomization until death due to any cause, assessed up to 3 year
    Title
    Objective response rate (ORR)
    Description
    the proportion of patients with complete response or partial response, using RECIST v 1.1.
    Time Frame
    Time Frame: from randomization up to progressive disease or EOT due to any cause, assessed up to 2 year
    Title
    Disease Control Rate (DCR)
    Description
    the proportion of patients with complete response, partial response or stable disease, using RECIST v 1.1.
    Time Frame
    from randomization up to progressive disease or EOT due to any cause, assessed up to 2 year
    Title
    Duration of Response (DOR)
    Description
    Cancer for the first time that assessment for CR or PR to the first evaluation for PD or any cause the time of death.
    Time Frame
    from randomization up to progressive disease or EOT due to any cause, assessed up to 2 year
    Title
    translational rate
    Description
    It refers to the proportion of all enrolled patients who underwent radical surgery/ablation therapy after medical treatment.
    Time Frame
    2-3 months
    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

    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; Understand the steps and content, and written informed consent signed voluntarily; Is confirmed by histopathology and/or cytology her2-negative or HER2 status unknown late recurrence or stomach esophagus stomach/integration of adenocarcinoma; In this research to define transfer of oligonucleotides definition: the primary lesion and regional lymph node metastasis of process to determine the surgeon can be cut or boundary can be cut, only intrahepatic metastasis and distant metastasis (metastases number 5 or less, a single lesion or less 5 cm in diameter.) And or retroperitoneal lymph node metastasis (16a2,16b1,16a1,16b2 metastasis), no other distant metastasis; At least one measurable lesion according to RECIST 1.1 criteria; No previous treatment with VEGFR-targeted drugs and PD-1/PD-L1 monoclonal antibodies. Patients who had relapsed more than 6 months after the completion of postoperative adjuvant chemotherapy with platinum or paclitaxel or fluorouracil and had no grade 2 or higher toxicity were eligible for enrollment. ECOG PS score: 0-1; Expected survival time ≥3 months; The main viscera function is good, namely into groups of related within 14 days before check index meet the following requirements: (1) hemoglobin ≥80 g/L; (2) neutrophil count >1.5×109/L; (3) platelet count ≥80×109/L; (4) Total bilirubin ≤2.5×ULN (upper limit of normal); (5) serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤5×ULN; (6) the endogenous creatinine clearance or 60 ml/min (Cockcroft - Gault formula); (7) Echocardiography: left ventricular ejection fraction (LVEF)≥50%; (8) Thyroid function indexes: thyroid stimulating hormone (TSH) and free thyroxine (FT3/FT4) were in the normal range or only mildly abnormal, without related clinical symptoms; (9) A body weight of 40 kg or more, or a BMI > 18.5; Exclusion Criteria: Patients with other malignant tumors in the past or at the same time, but have been cured of early tumors, including basal cell carcinoma of the skin and carcinoma in situ of the cervix, stage I lung cancer, stage I colorectal cancer and other tumors that do not affect the patient's life in the short term according to the investigator's judgment can be excluded; Participated in other drug clinical trials within four weeks; Multiple factors affecting oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction); Patients with a history of bleeding and any bleeding events of CTCAE5.0 grade 3 or higher within 4 weeks before screening; Metastasis in other distant sites, including but not limited to lung metastasis, brain metastasis, bone metastasis, distant lymph node metastasis, and peritoneal metastasis; Patients with hypertension not well controlled by single antihypertensive medication (systolic blood pressure >140 mmHg, diastolic blood pressure >90 mmHg); Patients with a history of unstable angina; Newly diagnosed angina pectoris within 3 months before screening or myocardial infarction within 6 months before screening; Arrhythmias (including QTcF ≥450 ms in men and ≥470 ms in women) required long-term use of antiarrhythmic drugs and New York Heart Association (NYHA) grade ≥II cardiac dysfunction; Long-term unhealed wounds or incompletely healed fractures; Imaging shows that the tumor has invaded the important blood vessels or the investigator judges that the patient's tumor has a high possibility of invading the important blood vessels during the treatment and causing fatal hemorrhage; Abnormal coagulation function, with bleeding tendency (14 days before enrollment must meet: INR in the normal range without anticoagulant or clinically insignificant abnormality); Patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin, or their analogues; International standardization in prothrombin time ratio (INR) under the premise of 1.5 or less, allowing purpose to prevent the use of low-dose warfarin (1 mg orally, once per day) or low-dose aspirin (amount does not exceed 100 mg daily); Occurrence of arterial/venous thrombosis events within 6 months before screening, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis (except for venous thrombosis caused by venous catheterization due to previous chemotherapy and judged by investigators to be cured), and pulmonary embolism; Urine routine showed urine protein ≥++ and confirmed 24-hour urine protein quantitation >1.0 g; Previous use of immune-targeted therapy drugs; Have a history of immunodeficiency or other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation; Patients with infectious pneumonia, non-infectious pneumonia, interstitial pneumonia and other patients requiring corticosteroids; A history of severe chronic autoimmune diseases, such as systemic lupus erythematosus; He had a history of inflammatory bowel disease such as ulcerative enteritis, Crohn's disease, and a history of chronic diarrhea such as irritable bowel syndrome. A history of sarcoidosis or tuberculosis; Patients with a history of active hepatitis B or C, and HIV infection; Good control of severe autoimmune disease, such as dermatitis, arthritis, psoriasis, etc can be into the group. Patients with hepatitis B virus titer <1000copy/ml were eligible for enrollment. Patients with hypersensitivity to human or murine monoclonal antibodies; Have a history of psychotropic drug abuse and cannot quit or have mental disorders; Patients who do not follow the doctor's advice, do not follow the prescribed medication, or have incomplete data, which may affect the efficacy or safety judgment; Concomitant diseases that, in the judgment of the investigator, seriously compromise patient safety or interfere with patient completion of the study.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Chen xiao feng, Ph.D
    Phone
    13585172066
    Email
    chenxiaofengnjmu@163.com

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

    Learn more about this trial

    XELOX Combined With Fruquintinib and Sintilimab Regimen Conversion Therapy for Gastric Cancer/Gastroesophageal Junction Adenocarcinoma Only With Liver and/or Retroperitoneal Lymph Node Metastasis, a Prospective Single-arm, Multicenter Study

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