Tislelizumab Combined With Lenvatinib for Perioperative Treatment of Resectable Primary Hepatocellular Carcinoma

A Prospective, One-arm, Phase II Clinical Study of Tislelizumab Combined With Lenvatinib for Perioperative Treatment of Resectable Primary Hepatocellular Carcinoma With a High Risk of Recurrence.

This is a prospective, one-arm, phase II clinical study of Tislelizumab combined with Lenvatinib for perioperative treatment of resectable primary hepatocellular carcinoma with a high risk of recurrence.

Study Overview

• Status: Not yet recruiting
• Conditions: Resectable Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Tislelizumab combined with Lenvatinib

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Insititute and Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients volunteered to participate in this study and signed informed consent;
• Age 18-75, male or female;
• ECOG PS score 0-1;
• Child-pugh liver function grading: Grade A
• The clinical diagnosis conforms to primary hepatocellular carcinoma (HCC) and the lesion conforms to the indications for resectable operation in the Guidelines for diagnosis and Treatment of HCC (2019) edition;

• According to the preoperative evaluation of the researcher, the patient had a high risk of recurrence and met at least one of the risk factors:

  Ⅰb: a single tumor diameter > 6.5 cm (except Mr Tian Bangxiong inflating),2-3 tumors with the maximum diameter ≤3cm;

  • a : tumor 2-3,biggest > 3 cm in diameter

  • b: tumor 4 or higher

    • a: vascular invasion to the naked eyes;
• According to RECIST 1.1 standard, patients have at least one measurable lesion (CT/MRI scan long diameter ≥10mm or CT/MRI scan short diameter ≥15mm for lymph node lesions, and the lesion has not received radiotherapy, freezing or other local treatments);
• Expected survival ≥ 6 months;
• 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 ≤ 2.5 times the upper limit of normal value (ULN); Urine protein <2+;If urinary protein ≥2+,24-hour quantitative urine protein must be ≤1g;

• Normal coagulation function, no active bleeding and thrombotic disease A. International standardized ratio INR≤1.5×ULN; B. Partial thromboplastin time APTT≤1.5×ULN; C. Prothrombin time PT≤1.5ULN;
• Women of childbearing age should agree to use contraceptives (such as intrauterine devices, contraceptives or condoms) during and within six months of the end of medication; Patients with negative serum or urine pregnancy tests within 7 days prior to study inclusion and who must be non-lactating, and males should agree to use contraceptives during the study period and for 6 months after the end of the study period;
• Subjects have good compliance and cooperate with the follow-up.

Exclusion Criteria:

• Have received radiotherapy, chemotherapy, concurrent chemoradiotherapy or other targeted therapies before;
• Known hepatobiliary cell carcinoma, sarcomatoid hepatocellular carcinoma, mixed cell carcinoma and fibre-lamellar cell carcinoma; Active malignancies other than HCC within 5 years or concurrently;
• Having hypertension that cannot be well controlled by antihypertensive drug therapy (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);Previous history of hypertension crisis or hypertensive encephalopathy;
• Subject has previous or concurrent malignancies (except cured basal cell carcinoma of skin and carcinoma in situ of the cervix);
• Previous treatment with Tislelizumab or other PD-1/PD-L1 treatment could not be enrolled; Subjects are known to have prior allergies to macromolecular protein reparations or to any Tislelizumab or Lenvatinib excipients;
• Subject has any active autoimmune disease or history of autoimmune disease (such as, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism; Subjects with vitiligo or childhood asthma have been completely relieved and may be included as adults without any intervention; Asthma requiring medical intervention with bronchodilators will not be included);
• Subjects are receiving immunosuppressive, or systemic, or absorbable local hormone therapy for immunosuppression purposes (>10mg/ day prednisone or other therapeutic hormones) and continue to receive such therapy within 2 weeks prior to enrollment;
• Ascites or pleural effusion with clinical symptoms require therapeutic puncture or drainage;

• Clinical symptoms or diseases of the heart that are not well controlled, such as:

  1. NYHA2 or above heart failure
  2. Unstable angina pectoris
  3. Myocardial infarction occurred within 1 year
  4. Patients with clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention;
• The patient currently (within 3 months) has gastrointestinal diseases such as esophageal varices, active gastric and duodenal ulcers, ulcerative colitis, portal hypertension, or active bleeding in unresected tumors, or other conditions determined by the researchers that may cause gastrointestinal bleeding or perforation;
• Past or present severe bleeding (>30 ml bleeding within 3 months), hemoptysis (>5 ml fresh blood within 4 weeks) or thromboembolic events (including stroke events and/or tia) within 12 months;
• Subject has active infection or unexplained fever of >38.5 degrees during screening and before first administration (subject's fever due to tumor can be enrolled according to the investigator's judgment);
• Patients with past or present objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radioactive pneumonia, drug related pneumonia, severe impairment of lung function, etc.;
• Subjects with congenital or acquired immune deficiency, such as HIV infection, or active hepatitis (transaminase does not meet the inclusion criteria, hepatitis B reference: HBV DNA≥1000/ml; Hepatitis C reference: HCV RNA≥103/ml);Chronic hepatitis B virus carriers, HBV DNA < 1000 IU/ml, must receive antiviral treatment at the same time during the test can be enrolled;
• Live vaccine is administered less than 4 weeks before or possibly during the study period;
• The subject has a known history of psychotropic substance abuse, alcohol abuse or drug abuse;
• The subject cannot or does not agree to bear the cost of the self-funded portion of the examination and treatment, except for the clinical study drug, combined chemotherapy and SAE related to the clinical study drug combined chemotherapy;
• Researchers think that should be left out in this study, the researchers determine, for example, the subjects have other factors that may result in this study were forced to midway termination, such as, other serious disease (including mental illness) need to merge treatment, there are serious abnormal laboratory examination, accompanied by factors such as family or society, will affect the safety of the subjects, or information and the collection of the sample.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Tislelizumab combined with Lenvatinib	Drug: Tislelizumab combined with Lenvatinib; Pre-operation: Tislelizumab, 200mg, iv,d1,q3w, 2-4 cycles; Lenvatinib,8mg/kg,po,qd,d1-d84. Operation Postoperation: 4-8 weeks after surgery, Tislelizumab, 200mg, iv,d1,q3w; Lenvatinib,8mg/kg,po,qd, up to one year.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety as measured by the number of grade 3 and grade 4 adverse events that occurred when subjects participated in the study, as defined by CTCAE v5.0.		36 months
Feasibility as measured by rate of enrollment	It's defined as a delay of surgery for any reason no more than 49 days compared to the specified planned surgery time (i.e., delay of surgery ≤42 days and scheduled surgery for 7 days).	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate(ORR)		2 months
1-year disease-free survival rate (1-year DFS%)		12 months
pathological complete response(pCR)		3 months
2-year disease-free survival rate (2-year DFS%)		24 months
disease-free survival(DFS)		24 months
adverse reactions	AEs and SAE	36 months

Other Outcome Measures

Outcome Measure	Time Frame
To explore genomic biomarkers of clinical remission/drug resistance (TMB, TNB, ITH, HLA subtype, HLA-LOH ) in combination with Tislelizumab and Lenvatinib.	36 months
Identification of tumor microenvironmental biomarkers (tumor Infiltrating lymphocytes, biomarkers expressed on T cells ) for clinical remission/drug resistance in combination with Tislelizumab and Lenvatinib.	36 months
To investigate the clinical efficacy of PD-L1 expression in predicting the combination of Tislelizumab and Lenvatinib.	36 months

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): April 30, 2021
• Primary Completion (ANTICIPATED): April 30, 2022
• Study Completion (ANTICIPATED): April 30, 2024

Study Registration Dates

• First Submitted: April 6, 2021
• First Submitted That Met QC Criteria: April 6, 2021
• First Posted (ACTUAL): April 8, 2021

Study Record Updates

• Last Update Posted (ACTUAL): April 8, 2021
• Last Update Submitted That Met QC Criteria: April 6, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Lenvatinib
• Other Study ID Numbers: GDS20201110564038

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No