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Tislelizumab Monotherapy or Combined With Lenvatinib as Neoadjuvant Therapy for Resectable Hepatocellular Carcinoma.

Primary Purpose

Resectable Hepatocellular Carcinoma

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Tislelizumab
Tislelizumab, Lenvatinib
Sponsored by
Tianjin Medical University Cancer Institute and Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Resectable Hepatocellular Carcinoma

Eligibility Criteria

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

Inclusion Criteria: Patients must have a known diagnosis of HCC as defined in the protocol Patients must be evaluated by the Department of Hepatobiliary Oncology, Tianjin Medical University Cancer Hospital to determine whether they can complete surgical treatment. Patients can be resectable in both oncology and surgery. At least ≥1 measurable lesion (RECIST 1.1) Age 18-75, male or female ECOG PS 0-1 Child-pugh A The function of vital organs meets the following requirements (excluding the use of any blood component and cell growth factor within 14 days) Blood routine: Neutrophils ≥1.5×109//L Platelet count ≥100×109/L Hemoglobin ≥90g/L Liver and kidney function: Serum creatinine (SCr) ≤ 1.5 times upper limit of normal value (ULN) or creatinine clearance ≥50 ml/min (Cockcroft-Gault formula) Total bilirubin (TBIL)≤ 1.5 times the upper limit of normal value (ULN) AST or ALT levels ≤ 3 times the upper limit of normal value (ULN) Normal coagulation function, International standardized ratio INR≤1.5×ULN or Prothrombin time PT≤1.5ULN Normal thyroid function is defined as thyroid stimulating hormone (TSH) within the normal range. Subjects whose baseline TSH is outside the normal range may be enrolled if total T3 (or FT3) and FT4 are within the normal range. Myocardial enzyme profiles were within the normal range (simple laboratory abnormalities that were not clinically significant were also allowed to be included) Patients who have progressed to PD or increased SD after 2 cycles of tislelizumab monotherapy must be willing to continue 2 cycles of tislelizumab and Lenvatinib combination therapy and be evaluated. Exclusion Criteria: Have received any systemic anticancer therapy or radiotherapy for their current tumor or other primary tumor in the 6 months prior to study entry. Tumor load or tumor growth rate was considered by the investigator to be insufficient to delay surgery. Had major surgery within 14 days prior to neoadjuvant therapy. Uncontrolled co-morbidities defined in the protocol and identified by the investigator. Receiving systemic steroid therapy or any other immunosuppressive therapy within 7 days prior to administration of the first dose of study therapy. Have had an active autoimmune disease requiring systemic treatment within the past 1 year. Have other malignancies that are known, developing and/or require aggressive treatment. Informed consent to encephalitis, meningitis, or uncontrolled seizures in the previous year. A history of interstitial lung disease (e.g., idiopathic pulmonary fibrosis, systemic pneumonia) or active non-infectious pneumonia requires immunosuppressive doses of glucocorticoids to assist in treatment. Bleeding from esophageal or fundus varices caused by portal hypertension in the past 6 months; Severe (G3) varicose veins were known on endoscopy within 3 months prior to initial administration; Patients with evidence of portal hypertension (including imaging findings of a large spleen diameter of more than 10cm and platelets of less than 100) were at high risk of bleeding as assessed by the investigators. History of arteriovenous thromboembolism events within the past 6 months, including myocardial infarction, unstable angina pectoris, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or any other severe thromboembolism. Implantable venous port or catheter-derived thrombosis, or superficial venous thrombosis, except in patients with stable thrombus after conventional anticoagulant therapy. Severe bleeding tendency or coagulopathy, or receiving thrombolytic therapy. Prophylactic use of low-dose, low-molecular heparin (e.g., enoxaparin 40 mg/ day) is permitted, except for vitamin K antagonists (e.g., warfarin). Long-term use of drugs that inhibit platelet function such as aspirin, dipyridamole or clopidogrel is required. Uncontrolled hypertension, systolic blood pressure > 140mmHg or diastolic blood pressure > 90 mmHg after optimal medical treatment, history of hypertensive crisis or hypertensive encephalopathy. Symptomatic congestive heart failure (New York Cardiological Association Grade II-IV), symptomatic or poorly controlled arrhythmias, history of congenital long QT syndrome or adjusted QTc > 500ms at screening (calculated using the Fridericia method). A previous history of gastrointestinal perforation and/or fistula within the past 6 months, a history of intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive enterectomy (partial resection of the colon or extensive resection of the small intestine with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    tislelizumab

    tislelizumab+lenvatinib

    Arm Description

    Received tislelizumab for 2 cycles, 200mg, iv, d1,Q3W. Patients achieved PR or reduced SD were enrolled in arm 1 and accepted surgery. After surgery, patients in arm 1 would receive tislelizumab as adjuvant therapy for 3-6 months.

    Received tislelizumab for 2 cycles, 200mg, iv, d1,Q3W. Patients achieved PD or increased SD were enrolled in arm 2 and continued to accept treatment with tislelizumab and lenvatinib for 2 cycles. After 2 cycles, patients would receive surgery according to their physical conditions. After surgery, patients in arm 2 would receive tislelizumab and lenvatinib as adjuvant therapy for 3-6 months.

    Outcomes

    Primary Outcome Measures

    MPR rate
    tumor necrosis rate ≥ 70%

    Secondary Outcome Measures

    1-year and 2-years DFS%
    1-year and 2-years disease-free survival rate
    ORR
    objective response rate
    Surgery delay rate
    Surgery was performed more than 28 days after the last cycle of neoadjuvant therapy
    MiVI rate
    Incidence of microvascular invasion
    mOS
    Median Overall survival
    AE and SAE
    adverse reactions

    Full Information

    First Posted
    March 29, 2023
    Last Updated
    March 29, 2023
    Sponsor
    Tianjin Medical University Cancer Institute and Hospital
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05807776
    Brief Title
    Tislelizumab Monotherapy or Combined With Lenvatinib as Neoadjuvant Therapy for Resectable Hepatocellular Carcinoma.
    Official Title
    A Phase II Prospective Study to Evaluate the Safety and Efficacy of Tislelizumab Monotherapy or Combined With Lenvatinib as Neoadjuvant Therapy for Resectable Hepatocellular Carcinoma.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    April 1, 2023 (Anticipated)
    Primary Completion Date
    December 31, 2023 (Anticipated)
    Study Completion Date
    December 31, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Tianjin Medical University Cancer Institute and Hospital

    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
    This is a phase II prospective study to evaluate the safety and efficacy of Tislelizumab monotherapy or combined with lenvatinib as neoadjuvant therapy for resectable hepatocellular carcinoma.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Resectable Hepatocellular Carcinoma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    50 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    tislelizumab
    Arm Type
    Experimental
    Arm Description
    Received tislelizumab for 2 cycles, 200mg, iv, d1,Q3W. Patients achieved PR or reduced SD were enrolled in arm 1 and accepted surgery. After surgery, patients in arm 1 would receive tislelizumab as adjuvant therapy for 3-6 months.
    Arm Title
    tislelizumab+lenvatinib
    Arm Type
    Experimental
    Arm Description
    Received tislelizumab for 2 cycles, 200mg, iv, d1,Q3W. Patients achieved PD or increased SD were enrolled in arm 2 and continued to accept treatment with tislelizumab and lenvatinib for 2 cycles. After 2 cycles, patients would receive surgery according to their physical conditions. After surgery, patients in arm 2 would receive tislelizumab and lenvatinib as adjuvant therapy for 3-6 months.
    Intervention Type
    Drug
    Intervention Name(s)
    Tislelizumab
    Intervention Description
    Tislelizumab 200mg, iv, d1, Q3W
    Intervention Type
    Drug
    Intervention Name(s)
    Tislelizumab, Lenvatinib
    Intervention Description
    Tislelizumab combined with lenvatinib: Tislelizumab 200mg, iv, d1, Q3W Lenvatinib 8mg,po,qd.
    Primary Outcome Measure Information:
    Title
    MPR rate
    Description
    tumor necrosis rate ≥ 70%
    Time Frame
    4 months
    Secondary Outcome Measure Information:
    Title
    1-year and 2-years DFS%
    Description
    1-year and 2-years disease-free survival rate
    Time Frame
    36 months
    Title
    ORR
    Description
    objective response rate
    Time Frame
    3 months
    Title
    Surgery delay rate
    Description
    Surgery was performed more than 28 days after the last cycle of neoadjuvant therapy
    Time Frame
    3 months
    Title
    MiVI rate
    Description
    Incidence of microvascular invasion
    Time Frame
    3 months
    Title
    mOS
    Description
    Median Overall survival
    Time Frame
    5 years
    Title
    AE and SAE
    Description
    adverse reactions
    Time Frame
    1 year

    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: Patients must have a known diagnosis of HCC as defined in the protocol Patients must be evaluated by the Department of Hepatobiliary Oncology, Tianjin Medical University Cancer Hospital to determine whether they can complete surgical treatment. Patients can be resectable in both oncology and surgery. At least ≥1 measurable lesion (RECIST 1.1) Age 18-75, male or female ECOG PS 0-1 Child-pugh A The function of vital organs meets the following requirements (excluding the use of any blood component and cell growth factor within 14 days) Blood routine: Neutrophils ≥1.5×109//L Platelet count ≥100×109/L Hemoglobin ≥90g/L Liver and kidney function: Serum creatinine (SCr) ≤ 1.5 times upper limit of normal value (ULN) or creatinine clearance ≥50 ml/min (Cockcroft-Gault formula) Total bilirubin (TBIL)≤ 1.5 times the upper limit of normal value (ULN) AST or ALT levels ≤ 3 times the upper limit of normal value (ULN) Normal coagulation function, International standardized ratio INR≤1.5×ULN or Prothrombin time PT≤1.5ULN Normal thyroid function is defined as thyroid stimulating hormone (TSH) within the normal range. Subjects whose baseline TSH is outside the normal range may be enrolled if total T3 (or FT3) and FT4 are within the normal range. Myocardial enzyme profiles were within the normal range (simple laboratory abnormalities that were not clinically significant were also allowed to be included) Patients who have progressed to PD or increased SD after 2 cycles of tislelizumab monotherapy must be willing to continue 2 cycles of tislelizumab and Lenvatinib combination therapy and be evaluated. Exclusion Criteria: Have received any systemic anticancer therapy or radiotherapy for their current tumor or other primary tumor in the 6 months prior to study entry. Tumor load or tumor growth rate was considered by the investigator to be insufficient to delay surgery. Had major surgery within 14 days prior to neoadjuvant therapy. Uncontrolled co-morbidities defined in the protocol and identified by the investigator. Receiving systemic steroid therapy or any other immunosuppressive therapy within 7 days prior to administration of the first dose of study therapy. Have had an active autoimmune disease requiring systemic treatment within the past 1 year. Have other malignancies that are known, developing and/or require aggressive treatment. Informed consent to encephalitis, meningitis, or uncontrolled seizures in the previous year. A history of interstitial lung disease (e.g., idiopathic pulmonary fibrosis, systemic pneumonia) or active non-infectious pneumonia requires immunosuppressive doses of glucocorticoids to assist in treatment. Bleeding from esophageal or fundus varices caused by portal hypertension in the past 6 months; Severe (G3) varicose veins were known on endoscopy within 3 months prior to initial administration; Patients with evidence of portal hypertension (including imaging findings of a large spleen diameter of more than 10cm and platelets of less than 100) were at high risk of bleeding as assessed by the investigators. History of arteriovenous thromboembolism events within the past 6 months, including myocardial infarction, unstable angina pectoris, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or any other severe thromboembolism. Implantable venous port or catheter-derived thrombosis, or superficial venous thrombosis, except in patients with stable thrombus after conventional anticoagulant therapy. Severe bleeding tendency or coagulopathy, or receiving thrombolytic therapy. Prophylactic use of low-dose, low-molecular heparin (e.g., enoxaparin 40 mg/ day) is permitted, except for vitamin K antagonists (e.g., warfarin). Long-term use of drugs that inhibit platelet function such as aspirin, dipyridamole or clopidogrel is required. Uncontrolled hypertension, systolic blood pressure > 140mmHg or diastolic blood pressure > 90 mmHg after optimal medical treatment, history of hypertensive crisis or hypertensive encephalopathy. Symptomatic congestive heart failure (New York Cardiological Association Grade II-IV), symptomatic or poorly controlled arrhythmias, history of congenital long QT syndrome or adjusted QTc > 500ms at screening (calculated using the Fridericia method). A previous history of gastrointestinal perforation and/or fistula within the past 6 months, a history of intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive enterectomy (partial resection of the colon or extensive resection of the small intestine with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Tianqiang Song, Doctor
    Phone
    +8618622221077
    Email
    tjchi@hotmail.com

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes

    Learn more about this trial

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