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HAIC or Lenvatinib Combined With Sintilimab for High Recurrence Risk Resectable Solitary Hepatocellular Carcinoma

Primary Purpose

Hepatocellular Carcinoma

Status
Not yet recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
HAIC
Sintilimab
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 Hepatocellular Carcinoma

Eligibility Criteria

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

Inclusion Criteria: Volunteer to join the study and signed the informed consent form Aged 18-75, male or female ECOG PS score 0-1 Child Pugh liver function Grade A Histopathology confirmed primary hepatocellular carcinoma (HCC) and the lesion met the indications for surgical resection in the Diagnostic and Therapeutic Norms for Primary Liver Cancer (2022) According to the investigator's assessment, there are the following high recurrence risk factors, Stage Ⅰ b: solitary tumor, with the largest diameter > 5cm At least one measurable lesion according to RECIST 1.1 (measurable lesion CT/MRI scan length diameter ≥ 10mm or lymph node lesion CT/MRI scan short diameter ≥ 15mm, and measurable lesion has not received radiotherapy, cryotherapy and other local treatments) Expected life ≥ 6 months Functions of important organs shall meet the following requirements (excluding the use of any blood component and cell growth factor within 14 days) Neutrophils ≥ 1500/mm3Platelet count ≥ 60,000/mm3Hemoglobin ≥ 5.6 mmol/L (9 g/dL); Serum creatinine (SCR) ≤ 1.5 times the 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); The level of AST or ALT ≤ 2.5 times the upper limit of normal value (ULN); Urine protein<2+; If urinary protein ≥ 2+, the 24-hour urine protein quantitative display must be ≤ 1g Normal coagulation function, no active bleeding and thrombosis disease International normalized ratio INR ≤ 1.5 × ULN; Partial thromboplastin time APTT ≤ 1.5 × ULN; Prothrombin time PT ≤ 1.5ULN; Women of childbearing age should agree to use contraceptive measures (such as intrauterine devices, contraceptives or condoms) during the medication period and within 6 months after the end of medication; If the serum or urine pregnancy test was negative within 7 days before the study included, and the patient must be a non lactating patient, the male should agree to use contraception during the study period and within 6 months after the end of the study period The subjects had good compliance and cooperated with follow-up. Exclusion Criteria: Previously received radiotherapy, chemotherapy, concurrent radiotherapy and chemotherapy or other targeted therapies Known hepatobiliary cell carcinoma, sarcomatoid HCC, mixed cell carcinoma and fibrolamellar cell carcinoma; Have other active malignant tumors except HCC within 5 years or at the same time Patients with hypertension who cannot be well controlled after antihypertensive drug treatment (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg); Previous hypertension crisis or hypertensive encephalopathy Patients had other malignant tumors in the past or at the same time (except cured skin basal cell carcinoma and cervical carcinoma in situ); Patients who had been treated with Sintilimab or other PD-1/PD-L1 inhibitors in the past could not be included; Known hypersensitivity to macromolecular protein preparations or any excipients of Sintilimab or lenvatinib Patients have any active autoimmune diseases or have a history of autoimmune diseases (Including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism; Patients with vitiligo or asthma in childhood has completely alleviated, without any intervention after adulthood can be included; Patients with asthma requiring medical intervention of bronchodilators cannot be included) Patients who are using immunosuppressive agents, or systemic or absorbable local hormone to achieve immunosuppressive purpose (Dose>10mg/day prednisone or other equivalent therapeutic hormones) and continue to use them within 2 weeks before enrollment Ascites or pleural effusion with clinical symptoms and requiring therapeutic puncture or drainage There are clinical symptoms or diseases of the heart that are not well controlled, such as: Heart failure above NYHA level 2 Unstable angina pectoris Myocardial infarction occurred within 1 year Clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention Patients having gastrointestinal diseases such as esophageal varices, active gastric and duodenal ulcers, ulcerative colitis, portal hypertension, or active bleeding from tumors that have not been removed, or other conditions that may cause gastrointestinal bleeding and perforation as determined by the investigator at present (within 3 months) Serious bleeding (>30 ml bleeding within 3 months), hemoptysis (>5 ml fresh blood within 4 weeks) or thromboembolism (including stroke and/or transient ischemic attack) occurred in the past or present Patients with active infection or fever of unknown origin>38.5℃during the screening period and before the first administration (according to the judgment of the investigator, subjects with fever due to tumor can be included) Patients with past or current objective evidence of pulmonary fibrosis history, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, and severe impairment of pulmonary function Patients with congenital or acquired immune deficiency, such as HIV infection, or active hepatitis (transaminase does not meet the inclusion criteria: HBV DNA ≥ 10e4/ml; HCV RNA ≥ 10e3/ml); Chronic hepatitis B virus carriers with HBV DNA<2000 IU/ml (<10e4 copies/ml) receive antiviral treatment at the same time during the trial can be included Live vaccine may be inoculated less than 4 weeks before the study medication or during the study period Known history of abuse of psychotropic substances, alcohol abuse or drug abuse Conditions should be excluded according to the judgment of the investigator, for example, according to the judgment of the investigator, the patient has other factors that may lead to the forced termination of the study, such as other serious diseases requiring combined treatment, serious laboratory examination abnormalities, and family or social factors, which may affect the safety of the subject, or the collection of data and samples.

Sites / Locations

  • Tianjin Medical University Cancer Institute & Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

experimental group1

experimental group 2

Arm Description

HAIC

Lenvatinib+Sintilimab

Outcomes

Primary Outcome Measures

1-year DFS rate
To evaluate the 1-year disease free survival rate of neoadjuvant treatment with HAIC or Lenvatinib combined with Sintilimab for of high recurrence risk resectable stage IB solitary hepatocellular carcinoma

Secondary Outcome Measures

Incidence of microvascular invasion
Defined as proportion of patients with microvascular invasion
Pathological complete response rate (pCR)
Defined as proportion of patients who have a best response of pCR
Objective response rate
Defined as proportion of patients who have a best response of CR or PR
2-year DFS rate
To evaluate the 2-year disease free survival rate of neoadjuvant treatment with HAIC or Lenvatinib combined with Sintilimab for of high recurrence risk resectable stage IB solitary hepatocellular carcinoma
2-year OS rate
To evaluate the 2-year overall survival rate of neoadjuvant treatment with HAIC or Lenvatinib combined with Sintilimab for of high recurrence risk resectable stage IB solitary hepatocellular carcinoma
Adverse Events (AEs)
Defined as the proportion of patients with AE, treatment-related AE (TRAE), immune-related AE (irAE), serious adverse event (SAE), assessed by NCI CTCAE v5.0 and complications of surgery

Full Information

First Posted
November 10, 2022
Last Updated
November 10, 2022
Sponsor
Tianjin Medical University Cancer Institute and Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05621499
Brief Title
HAIC or Lenvatinib Combined With Sintilimab for High Recurrence Risk Resectable Solitary Hepatocellular Carcinoma
Official Title
The Safety and Efficacy of HAIC or Lenvatinib Combined With Sintilimab as a Neoadjuvant Therapy for High Recurrence Risk Resectable Stage IB Solitary Hepatocellular Carcinoma: a Prospective, Randomized, Two Cohort, Exploratory Study
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 2022 (Anticipated)
Primary Completion Date
November 2023 (Anticipated)
Study Completion Date
November 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
To evaluate the safety and efficacy of HAIC or Lenvatinib combined with Sintilimab as a neoadjuvant therapy for high recurrence risk resectable stage IB solitary hepatocellular carcinoma

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
experimental group1
Arm Type
Experimental
Arm Description
HAIC
Arm Title
experimental group 2
Arm Type
Experimental
Arm Description
Lenvatinib+Sintilimab
Intervention Type
Drug
Intervention Name(s)
HAIC
Intervention Description
Oxaliplatin 85 mg/m2, LV 400 mg/ m2, 5-FU 400 mg/m2 bolus and then 2400 mg/m2 as 46h continuous infusion,Q3W,a total of 2 cycles
Intervention Type
Drug
Intervention Name(s)
Sintilimab
Other Intervention Name(s)
IBI308
Intervention Description
200mg,iv,d1,q3w,a total of 3 cycles
Intervention Type
Drug
Intervention Name(s)
Lenvatinib
Intervention Description
12 or 8mg/kg,po,qd,a total of 3 cycles
Primary Outcome Measure Information:
Title
1-year DFS rate
Description
To evaluate the 1-year disease free survival rate of neoadjuvant treatment with HAIC or Lenvatinib combined with Sintilimab for of high recurrence risk resectable stage IB solitary hepatocellular carcinoma
Time Frame
up to 1 years
Secondary Outcome Measure Information:
Title
Incidence of microvascular invasion
Description
Defined as proportion of patients with microvascular invasion
Time Frame
Up to 3 years
Title
Pathological complete response rate (pCR)
Description
Defined as proportion of patients who have a best response of pCR
Time Frame
up to 1 years
Title
Objective response rate
Description
Defined as proportion of patients who have a best response of CR or PR
Time Frame
Up to 1 years
Title
2-year DFS rate
Description
To evaluate the 2-year disease free survival rate of neoadjuvant treatment with HAIC or Lenvatinib combined with Sintilimab for of high recurrence risk resectable stage IB solitary hepatocellular carcinoma
Time Frame
Up to 3 years
Title
2-year OS rate
Description
To evaluate the 2-year overall survival rate of neoadjuvant treatment with HAIC or Lenvatinib combined with Sintilimab for of high recurrence risk resectable stage IB solitary hepatocellular carcinoma
Time Frame
Up to 3 years
Title
Adverse Events (AEs)
Description
Defined as the proportion of patients with AE, treatment-related AE (TRAE), immune-related AE (irAE), serious adverse event (SAE), assessed by NCI CTCAE v5.0 and complications of surgery
Time Frame
Up to 3 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: Volunteer to join the study and signed the informed consent form Aged 18-75, male or female ECOG PS score 0-1 Child Pugh liver function Grade A Histopathology confirmed primary hepatocellular carcinoma (HCC) and the lesion met the indications for surgical resection in the Diagnostic and Therapeutic Norms for Primary Liver Cancer (2022) According to the investigator's assessment, there are the following high recurrence risk factors, Stage Ⅰ b: solitary tumor, with the largest diameter > 5cm At least one measurable lesion according to RECIST 1.1 (measurable lesion CT/MRI scan length diameter ≥ 10mm or lymph node lesion CT/MRI scan short diameter ≥ 15mm, and measurable lesion has not received radiotherapy, cryotherapy and other local treatments) Expected life ≥ 6 months Functions of important organs shall meet the following requirements (excluding the use of any blood component and cell growth factor within 14 days) Neutrophils ≥ 1500/mm3Platelet count ≥ 60,000/mm3Hemoglobin ≥ 5.6 mmol/L (9 g/dL); Serum creatinine (SCR) ≤ 1.5 times the 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); The level of AST or ALT ≤ 2.5 times the upper limit of normal value (ULN); Urine protein<2+; If urinary protein ≥ 2+, the 24-hour urine protein quantitative display must be ≤ 1g Normal coagulation function, no active bleeding and thrombosis disease International normalized ratio INR ≤ 1.5 × ULN; Partial thromboplastin time APTT ≤ 1.5 × ULN; Prothrombin time PT ≤ 1.5ULN; Women of childbearing age should agree to use contraceptive measures (such as intrauterine devices, contraceptives or condoms) during the medication period and within 6 months after the end of medication; If the serum or urine pregnancy test was negative within 7 days before the study included, and the patient must be a non lactating patient, the male should agree to use contraception during the study period and within 6 months after the end of the study period The subjects had good compliance and cooperated with follow-up. Exclusion Criteria: Previously received radiotherapy, chemotherapy, concurrent radiotherapy and chemotherapy or other targeted therapies Known hepatobiliary cell carcinoma, sarcomatoid HCC, mixed cell carcinoma and fibrolamellar cell carcinoma; Have other active malignant tumors except HCC within 5 years or at the same time Patients with hypertension who cannot be well controlled after antihypertensive drug treatment (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg); Previous hypertension crisis or hypertensive encephalopathy Patients had other malignant tumors in the past or at the same time (except cured skin basal cell carcinoma and cervical carcinoma in situ); Patients who had been treated with Sintilimab or other PD-1/PD-L1 inhibitors in the past could not be included; Known hypersensitivity to macromolecular protein preparations or any excipients of Sintilimab or lenvatinib Patients have any active autoimmune diseases or have a history of autoimmune diseases (Including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism; Patients with vitiligo or asthma in childhood has completely alleviated, without any intervention after adulthood can be included; Patients with asthma requiring medical intervention of bronchodilators cannot be included) Patients who are using immunosuppressive agents, or systemic or absorbable local hormone to achieve immunosuppressive purpose (Dose>10mg/day prednisone or other equivalent therapeutic hormones) and continue to use them within 2 weeks before enrollment Ascites or pleural effusion with clinical symptoms and requiring therapeutic puncture or drainage There are clinical symptoms or diseases of the heart that are not well controlled, such as: Heart failure above NYHA level 2 Unstable angina pectoris Myocardial infarction occurred within 1 year Clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention Patients having gastrointestinal diseases such as esophageal varices, active gastric and duodenal ulcers, ulcerative colitis, portal hypertension, or active bleeding from tumors that have not been removed, or other conditions that may cause gastrointestinal bleeding and perforation as determined by the investigator at present (within 3 months) Serious bleeding (>30 ml bleeding within 3 months), hemoptysis (>5 ml fresh blood within 4 weeks) or thromboembolism (including stroke and/or transient ischemic attack) occurred in the past or present Patients with active infection or fever of unknown origin>38.5℃during the screening period and before the first administration (according to the judgment of the investigator, subjects with fever due to tumor can be included) Patients with past or current objective evidence of pulmonary fibrosis history, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, and severe impairment of pulmonary function Patients with congenital or acquired immune deficiency, such as HIV infection, or active hepatitis (transaminase does not meet the inclusion criteria: HBV DNA ≥ 10e4/ml; HCV RNA ≥ 10e3/ml); Chronic hepatitis B virus carriers with HBV DNA<2000 IU/ml (<10e4 copies/ml) receive antiviral treatment at the same time during the trial can be included Live vaccine may be inoculated less than 4 weeks before the study medication or during the study period Known history of abuse of psychotropic substances, alcohol abuse or drug abuse Conditions should be excluded according to the judgment of the investigator, for example, according to the judgment of the investigator, the patient has other factors that may lead to the forced termination of the study, such as other serious diseases requiring combined treatment, serious laboratory examination abnormalities, and family or social factors, which may affect the safety of the subject, or the collection of data and samples.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yunlong Cui
Phone
18622228633
Email
ningyunlong@163.com
Facility Information:
Facility Name
Tianjin Medical University Cancer Institute & Hospital
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300060
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yunlong Cui
Phone
18622228633
Email
ningyunlong@163.com

12. IPD Sharing Statement

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HAIC or Lenvatinib Combined With Sintilimab for High Recurrence Risk Resectable Solitary Hepatocellular Carcinoma

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