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Gemox Combined With Anlotinib and Sintilimab in Advanced cHCC-ICC

Primary Purpose

Combined Hepatocellular Cholangiocarcinoma

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
gemcitabine ,oxaliplatin,anlotinib,Sintilimab
Sponsored by
Sichuan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Combined Hepatocellular Cholangiocarcinoma

Eligibility Criteria

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

Inclusion Criteria: .Age 18-75 years; .Histologically or cytologically confirmed diagnosis of aCombined hepatocellular-cholangiocarcinoma; .Non resectable or metastatic cHCC-ICC patients who have not received systemic treatment or first-line treatment progress (only non arotinib Targeted therapy or non GEMOX chemotherapy) in the past, and have at least one measurable lesion (RECIST v1.1); .Life expectancy ≥ 3 months; .ECOG PS 0-1; .Child Pugh A/B ≤ 7; .Adequate organ function including the following:Total bilirubin ≤1.5 times upper limit of normal (ULN),Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3×ULN,Alkaline phosphatase≤2.5×ULN (If the tumor invaded the liver, ≤3×ULN), Serum creatinine≤1.5×ULN,Serum amylase and lipase≤1.5×ULN,International standardized ratio (INR)/partial prothrombin time (PTT)≤1.5×ULN;Platelet count ≥ 75,000 /mm3.Hemoglobin (Hb) ≥ 9 g/dL.Absolute neutrophil count (ANC) ≥ 1500/mm3. .Strict contraception. .Patients must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure. Exclusion Criteria: Has a history of severe allergic reactions to chimeric, human or humanized antibodies, or fusion proteins. Pregnant or lactating women, men and women of childbearing age who are unwilling or unable to take effective contraceptive measures; History of other malignant tumors in the past 5 years, except for malignant tumors that have received treatment for the purpose of cure, and have no known active diseases for ≥ 5 years before the first administration, and have a low potential risk of recurrence; Fully treated non Melanoma skin cancer or malignant lentigo without disease evidence; Fully treated Carcinoma in situ, no disease evidence; Moderate or higher amounts of pleural and ascitic fluid with clinical symptoms; Active bleeding or abnormal coagulation function (PT>16s, APTT>43s, INR>1.5) × ULN), with a tendency to bleed or undergoing thrombolysis, anticoagulation, or antiplatelet therapy; Hepatic encephalopathy; Within the past 6 months, there has been a history of gastrointestinal bleeding or a clear tendency for gastrointestinal bleeding, such as known local active ulcer lesions, fecal occult blood+or above, which cannot be included in the group; If there is continuous fecal occult blood, gastroscopy should be performed; Patients with severe gastroesophageal varices who require interventional treatment; Untreated active hepatitis B. (Note: Hepatitis B patients who receive antiviral treatment and whose HBV Viral load is less than 2000IU/ml can be allowed to participate in the study) Active hepatitis C, that is, those who are anti-HCV positive or HCV-RNA positive and have abnormal liver function; Having a history of psychotropic substance abuse, unable to quit, or having a history of mental disorders; Patients who received solid organ transplantation or bone marrow transplantation, or had active autoimmune diseases requiring systemic Sex therapy within 2 years before the first administration; Existence of immune deficiency diseases or HIV infection; There has been objective evidence that Pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia and serious impairment of lung function exist in the past or at present; Major surgery on the liver or other parts has been performed within 4 weeks before the first administration, or minor surgery (such as simple resection, tooth extraction, etc.) has been performed within 1 week before the first administration; Received the vaccine within 30 days before the first administration; Abdominal fistula, gastrointestinal perforation, or abdominal abscess occurred within 4 weeks prior to the first administration; For any significant clinical and laboratory abnormalities, the researchers believe that they will affect the safety evaluators, such as: active infection requiring systemic Sex therapy, uncontrollable diabetes, hypertension patients who cannot fall to the normal range (systolic pressure>140mmHg, diastolic pressure>90mmHg), myocardial infarction within 6 months, thyroid dysfunction (>NCI CTCAE v4.0 Level 1 standard) after treatment with two or less antihypertensive drugs; Researchers believe that it is not suitable for inclusion in the study.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Gemox combined with Anlotinib and Sintilimab

    Arm Description

    Gemox chemotherapy(gemcitabine 1g/m2 ivgtt d1,d8 +oxaliplatin 85g/m2 ivgtt d1,q3w,anlotinib (8mg po d1-14 q3w )and Sintilimab (200mg ivgtt d1 q3w)

    Outcomes

    Primary Outcome Measures

    ORR
    Objective Response Rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version. 1.1

    Secondary Outcome Measures

    Safety and tolerability
    Incidence of Treatment-Emergent Adverse Events,Version 5.0 and AEs leading to dose interruption or discontinuation.
    PFS
    Progression-free survival is determined from the date of treatment to PD or death from any cause
    OS
    OS is the time interval from the start of treatment to death due to any reason or lost of follow-up

    Full Information

    First Posted
    July 10, 2023
    Last Updated
    September 10, 2023
    Sponsor
    Sichuan University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06033118
    Brief Title
    Gemox Combined With Anlotinib and Sintilimab in Advanced cHCC-ICC
    Official Title
    Gemox Combined With Anlotinib and Sintilimab in Advanced Combined Hepatocellular-cholangiocarcinoma: an Exploratory Study
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 1, 2023 (Anticipated)
    Primary Completion Date
    July 31, 2025 (Anticipated)
    Study Completion Date
    August 1, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Sichuan 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 Evaluate the Efficacy and Safety of Gemox combined with Anlotinib and Sintilimab as first-lineTherapy for Patients With advanced combined hepatocellular-cholangiocarcinoma.
    Detailed Description
    Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) accounts for 0.4%-14.2% of primary hepatocellular carcinoma. As imaging and pathological diagnostic techniques for liver tumors have improved, the detection rate of cHCC-CCA puncture biopsies and surgical procedures has increased. Oxaliplatin-containing chemotherapy was previously recommended for the treatment of advanced cHCC-ICC, but its efficacy was not satisfactory. Targeted therapy and immunotherapy have made breakthroughs in both advanced HCC and CCA, providing a new direction for exploration in the treatment of advanced cHCC-CCA. Currently, targeted combination immunotherapy has become the preferred first-line treatment strategy for advanced HCC. Chemotherapy combined with immunotherapy is also the preferred first-line treatment option for advanced CCA. To balance the treatment of HCC and ICC, this study further investigates the efficacy and safety of Gemox chemotherapy combined with anlotinib and Sintilimab(anti-PD-1 monoclonal antibody) immunotherapy in advanced cHCC-ICC, to provide a new treatment strategy and reference for the clinical treatment of advanced cHCC-CCA patients.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Combined Hepatocellular Cholangiocarcinoma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, 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
    Gemox combined with Anlotinib and Sintilimab
    Arm Type
    Experimental
    Arm Description
    Gemox chemotherapy(gemcitabine 1g/m2 ivgtt d1,d8 +oxaliplatin 85g/m2 ivgtt d1,q3w,anlotinib (8mg po d1-14 q3w )and Sintilimab (200mg ivgtt d1 q3w)
    Intervention Type
    Drug
    Intervention Name(s)
    gemcitabine ,oxaliplatin,anlotinib,Sintilimab
    Intervention Description
    Gemox chemotherapy(gemcitabine 1g/m2 ivgtt d1,d8 +oxaliplatin 85g/m2 ivgtt d1,q3w,anlotinib (8mg po d1-14 q3w )and Sintilimab (200mg ivgtt d1 q3w)
    Primary Outcome Measure Information:
    Title
    ORR
    Description
    Objective Response Rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version. 1.1
    Time Frame
    Every 2 cycles (each cycle is 21 days)starting from the first cycle, and every 3 cycles after 6 cycles
    Secondary Outcome Measure Information:
    Title
    Safety and tolerability
    Description
    Incidence of Treatment-Emergent Adverse Events,Version 5.0 and AEs leading to dose interruption or discontinuation.
    Time Frame
    3 months after the last administration of drugs
    Title
    PFS
    Description
    Progression-free survival is determined from the date of treatment to PD or death from any cause
    Time Frame
    Every 2 cycles(each cycle is 21 days) starting from the first cycle, and every 3 cycles after 6 cycles
    Title
    OS
    Description
    OS is the time interval from the start of treatment to death due to any reason or lost of follow-up
    Time Frame
    Every 2 cycles(each cycle is 21 days) starting from the first cycle, and every 3 cycles after 6 cycles

    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; .Histologically or cytologically confirmed diagnosis of aCombined hepatocellular-cholangiocarcinoma; .Non resectable or metastatic cHCC-ICC patients who have not received systemic treatment or first-line treatment progress (only non arotinib Targeted therapy or non GEMOX chemotherapy) in the past, and have at least one measurable lesion (RECIST v1.1); .Life expectancy ≥ 3 months; .ECOG PS 0-1; .Child Pugh A/B ≤ 7; .Adequate organ function including the following:Total bilirubin ≤1.5 times upper limit of normal (ULN),Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3×ULN,Alkaline phosphatase≤2.5×ULN (If the tumor invaded the liver, ≤3×ULN), Serum creatinine≤1.5×ULN,Serum amylase and lipase≤1.5×ULN,International standardized ratio (INR)/partial prothrombin time (PTT)≤1.5×ULN;Platelet count ≥ 75,000 /mm3.Hemoglobin (Hb) ≥ 9 g/dL.Absolute neutrophil count (ANC) ≥ 1500/mm3. .Strict contraception. .Patients must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure. Exclusion Criteria: Has a history of severe allergic reactions to chimeric, human or humanized antibodies, or fusion proteins. Pregnant or lactating women, men and women of childbearing age who are unwilling or unable to take effective contraceptive measures; History of other malignant tumors in the past 5 years, except for malignant tumors that have received treatment for the purpose of cure, and have no known active diseases for ≥ 5 years before the first administration, and have a low potential risk of recurrence; Fully treated non Melanoma skin cancer or malignant lentigo without disease evidence; Fully treated Carcinoma in situ, no disease evidence; Moderate or higher amounts of pleural and ascitic fluid with clinical symptoms; Active bleeding or abnormal coagulation function (PT>16s, APTT>43s, INR>1.5) × ULN), with a tendency to bleed or undergoing thrombolysis, anticoagulation, or antiplatelet therapy; Hepatic encephalopathy; Within the past 6 months, there has been a history of gastrointestinal bleeding or a clear tendency for gastrointestinal bleeding, such as known local active ulcer lesions, fecal occult blood+or above, which cannot be included in the group; If there is continuous fecal occult blood, gastroscopy should be performed; Patients with severe gastroesophageal varices who require interventional treatment; Untreated active hepatitis B. (Note: Hepatitis B patients who receive antiviral treatment and whose HBV Viral load is less than 2000IU/ml can be allowed to participate in the study) Active hepatitis C, that is, those who are anti-HCV positive or HCV-RNA positive and have abnormal liver function; Having a history of psychotropic substance abuse, unable to quit, or having a history of mental disorders; Patients who received solid organ transplantation or bone marrow transplantation, or had active autoimmune diseases requiring systemic Sex therapy within 2 years before the first administration; Existence of immune deficiency diseases or HIV infection; There has been objective evidence that Pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia and serious impairment of lung function exist in the past or at present; Major surgery on the liver or other parts has been performed within 4 weeks before the first administration, or minor surgery (such as simple resection, tooth extraction, etc.) has been performed within 1 week before the first administration; Received the vaccine within 30 days before the first administration; Abdominal fistula, gastrointestinal perforation, or abdominal abscess occurred within 4 weeks prior to the first administration; For any significant clinical and laboratory abnormalities, the researchers believe that they will affect the safety evaluators, such as: active infection requiring systemic Sex therapy, uncontrollable diabetes, hypertension patients who cannot fall to the normal range (systolic pressure>140mmHg, diastolic pressure>90mmHg), myocardial infarction within 6 months, thyroid dysfunction (>NCI CTCAE v4.0 Level 1 standard) after treatment with two or less antihypertensive drugs; Researchers believe that it is not suitable for inclusion in the study.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Yu Yang, M.D
    Phone
    18980606616
    Email
    yangyuflying@hotmail.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Qiuji Wu, M.D
    Phone
    18380325408
    Email
    anyandywqj@163.com

    12. IPD Sharing Statement

    Learn more about this trial

    Gemox Combined With Anlotinib and Sintilimab in Advanced cHCC-ICC

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