Clinical trial NCT06253598: Efficacy and Safety of Intratumoral Injection of Recombinant Human Adenovirus Type 5 Combined With Tislelizumab and Lenvatinib in the Treatment of Advanced Hepatocellular Carcinoma
Official title: Efficacy and Safety of Intratumoral Injection of Recombinant Human Adenovirus Type 5 Combined With Tislelizumab and Lenvatinib in the Treatment of Advanced Hepatocellular Carcinoma: a Single-center, Prospective, Single-arm Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Lead sponsor: The First Affiliated Hospital of Bengbu Medical University
Sponsor class: OTHER
First posted: 2024-02-12
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This prospective, single-arm study was aimed to evaluate the efficacy of recombinant human adenovirus type 5 injection combined with tislelizumab and lenvatinib in the treatment of advanced hepatocellular carcinoma. The recombinant human adenovirus type 5 was administered intratumorally on day 1 and 5 in cycle 1 and cycle 2. Lenvatinib was administered orally once daily started on day 1 of cycle 1 .Tislelizumab was administered intravenously every 3 week started on day 1 of cycle 3. The patient accepted the therapy until disease progression or unacceptable toxicity occurred or meet the end point of the study. The primary end point was ORR assessed by investigator using RECIST v1.1 .


Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years old, and ≤75 years old, regardless of gender;
2. Primary hepatocellular carcinoma confirmed by histology or imaging;
3. Patients with advanced hepatocellular carcinoma who have not received oncolytic viruses, immutherapy drugs (including anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs), and systemic therapy (such as anti-VEGF /VEGFR monoclonal antibodies, anti- VEGFR-TKI drugs, chemotherapy);
4. ECOG performance status 0-1;
5. Child-Pugh score ≤7;
6. There was at least one measurable target lesion according to RECIST 1.1 criteria, and at least one lesion was ≥ 10 mm;
7. The expected survival time was ≥3 months;
8. Laboratory tests during the screening period met the following criteria:

   i. White blood cell count ≥ 3.0×10\^9 /L, absolute neutrophil count ≥1.5×10\^9/L, platelet count ≥ 75×10\^9/L, hemoglobin \> 90g/L

   ii. INR≤1.5 and APTT≤1.5 times upper limit of normal or partial prothrombin time (PTT) ≤1.5 times upper limit of normal;

   iii. Total bilirubin ≤2.5 times upper limit of normal; ALT and AST≤5 times upper limit of normal (ULN); Serum creatinine ≤1.5 times the upper limit of normal.
9. They volunteered to participate in this study and signed informed consent.

Exclusion Criteria:

1. Pregnant or lactating women, men or women unwilling to use effective contraception;
2. Diffuse liver cancer or tumor is not suitable for RECIST 1.1 criteria;
3. Patients who have previously received an oncolytic viral agent such as T-VEC;
4. Known allergy to the study drug or its active ingredient, history of allergy to the same biological agent;
5. HBV DNA quantitation ≥1000 copies.
6. Imaging showed portal vein tumor thrombus more than half of the lumen, inferior vena cava tumor thrombus or heart involvement.
7. The patient has had grade ≥2 hepatic encephalopathy within 12 months or currently requires medication to prevent or control hepatic encephalopathy.
8. Confirmed active tuberculosis (TB), known human immunodeficiency virus (HIV) positive patients, and other serious infections requiring treatment;
9. A history of immunodeficiency or autoimmune disease, or long-term systemic steroid therapy or any form of immunosuppressive therapy within 7 days before enrollment;
10. A history of other (including unknown primary) malignancies, except for Cured non- melanoma skin malignancies, carcinoma in situ of the cervix, radical stage I uterine cancer, radical ductal carcinoma in situ or lobular carcinoma in situ of the breast (without any systemic treatment), localized prostate cancer that is currently considered cured after radical surgery, and other solid tumors that have been treated with radical surgery for more than 5 years without evidence of recurrence;
11. Known tumors of the central nervous system, including metastatic brain tumors;
12. Accompanied by any unstable systemic disease, including but not limited to: Severe infections, patients with hypertension whose blood pressure cannot be lowered to normal after antihypertensive treatment, uncontrolled diabetes mellitus, unstable angina pectoris, cerebrovascular accident or transient ischemic attack, myocardial infarction (a history of myocardial infarction of 6 months or more is allowed), congestive heart failure, serious arrhythmias requiring medical treatment, renal or metabolic diseases;
13. With medical contraindications to any contrast-enhanced imaging (CT or MRI);
14. Participants who had participated in an interventional clinical trial within 30 days before screening (Note: Participants who were already in the follow-up phase of the clinical trial could participate in this trial if it was 4 weeks after the last dose of the previous investigational drug).

Primary outcomes:
measure: Objective response rate using RECIST v1.1
timeFrame: 3 years
Secondary outcomes:
measure: DOT
timeFrame: 3 years
measure: DOR
timeFrame: 3 years
measure: DCR
timeFrame: 3 years
measure: PFS
timeFrame: 3 years
measure: 1-year overall survival rate
timeFrame: 1years
measure: AE
timeFrame: 3 years
Other outcomes:
Locations:
Study officials:
References: