Clinical trial NCT06685354: Sequential T and I With H101 Via HAI for BCLC C Stage HCC: A Prospective Single-Center Single-Arm Pilot Study
Official title: Sequential Targeted and Immunotherapy With Recombined Human Type 5 Adenovirus Via Hepatic Arterial Infusion for BCLC Stage C Hepatocellular Carcinoma: A Prospective Single-Center Single-Arm Pilot Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Hepatocellular Carcinoma (HCC)
Lead sponsor: Henan Cancer Hospital
Sponsor class: OTHER_GOV
First posted: 2024-11-12
Enrollment: 11
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: Indication: Hepatocellular carcinoma (HCC) patients at Barcelona Clinic Liver Cancer (BCLC) stage C.

Study Objectives: This study aims to use a prospective single-center single-arm pilot approach to preliminarily obtain data on the recent efficacy and safety of sequential targeted and immunotherapy with recombinant human type 5 adenovirus (H101) administered via hepatic arterial infusion for BCLC stage C HCC. Additionally, it will explore changes in the patients\&#39; immune systems before and after treatment, providing a basis for formal research.

Study Content: The study will use a prospective single-center single-arm pilot design to preliminarily assess the efficacy of sequential targeted and immunotherapy with H101 via hepatic arterial infusion in BCLC stage C HCC. Primary efficacy endpoints include: Objective Response Rate (ORR). Secondary efficacy endpoints include: Disease Control Rate (DCR), Duration of Response (DOR), Progression-Free Survival (PFS) at 6 months and 12 months, Overall Survival (OS) at 6 months and 12 months, Median Progression-Free Survival (mPFS), Liver-specific PFS. Additionally, the study will collect data on safety and tolerability and will explore changes in peripheral blood lymphocytes before and after treatment.

Expected Objectives: Efficacy and Safety Assessment: To preliminarily gather data on the short-term efficacy, safety, and tolerability of sequential targeted and immunotherapy using hepatic arterial infusion of H101 in patients with BCLC stage C HCC. This includes assessing primary efficacy endpoints (e.g., objective response rate) and secondary efficacy endpoints (e.g., disease control rate, duration of response, progression-free survival, overall survival, etc.). Immune System Changes: To investigate the patterns of peripheral blood lymphocyte changes before and after treatment.


Eligibility criteria: Inclusion Criteria:

1. Voluntarily participating in the study, signing the informed consent form, and willing to undergo follow-up;
2. Age ≥ 18 years and ≤ 75 years, regardless of gender;
3. Clinically or pathologically confirmed BCLC Stage C hepatocellular carcinoma, with no prior TACE or systemic treatment;
4. Baseline imaging (MRI or CT) showing measurable lesions with a longest diameter ≥ 1 cm;
5. Child-Pugh score ≤ 7 (Child-Pugh A-B);
6. Liver tumor burden not exceeding 50% of the liver volume;
7. Able to swallow pills normally;
8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1 (see Appendix 1 for ECOG PS scoring);
9. Expected survival ≥ 3 months;
10. Major organ function meeting the following criteria (no blood transfusions or blood products, and no medication correction within 2 weeks prior to treatment): Hematology: Absolute neutrophil count ≥ 1.5 × 10\^9/L, platelet count \&gt; 80 × 10\^9/L, hemoglobin ≥ 90 g/L; Biochemistry: Serum albumin ≥ 28 g/L, Thyroid-stimulating hormone (TSH) ≤ 1 × ULN (if abnormal, free triiodothyronine (FT3) and free thyroxine (FT4) levels should also be checked. If FT3 and FT4 levels are normal, the patient can be included); Bilirubin ≤ 1.5 × ULN (7 days before first dose); Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 3 × ULN (7 days before first dose); Alkaline phosphatase (AKP) ≤ 2.5 × ULN; Serum creatinine ≤ 1.5 × ULN;
11. Women of childbearing potential: Must agree to use effective contraception or abstain from heterosexual intercourse from signing the informed consent form until at least 120 days after the last dose of the study drug. A negative serum human chorionic gonadotropin (HCG) test within one week prior to enrollment is required, and the patient must not be breastfeeding. Women who are menstruating, have not reached menopause (defined as ≥ 12 months of amenorrhea without other causes), and have not undergone sterilization procedures (such as hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) are considered to be of childbearing potential;
12. For male participants with partners of childbearing potential, they must agree to use effective contraception or abstain from heterosexual intercourse from signing the informed consent form until at least 120 days after the last dose of the study drug. During this period, male participants must also agree not to donate sperm.

Exclusion Criteria:

1. Significant clinical bleeding symptoms or clear gastrointestinal bleeding tendencies (e.g., severe esophageal or gastric varices, active gastrointestinal ulcers, or vasculitis) within 3 months before enrollment. If fecal occult blood is positive during screening, a recheck is required, and if still positive, gastroscopy must be performed.
2. Active autoimmune diseases or history of autoimmune diseases with potential for recurrence (including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, and hypothyroidism - only subjects controlled by hormone replacement therapy are allowed). Subjects with skin conditions requiring no systemic treatment (e.g., vitiligo, psoriasis, alopecia), childhood asthma fully resolved, and no intervention needed in adulthood may be included. Asthma patients requiring bronchodilators for medical intervention cannot be included.
3. Use of immunosuppressants or systemic steroids within 2 weeks before enrollment for immunosuppressive purposes (dose \&gt;10mg/day of prednisone or equivalent).
4. Allergy to any monoclonal antibodies, anti-angiogenesis targeted drugs, or excipients.
5. Known history of central nervous system metastases or hepatic encephalopathy.
6. Patients who are preparing for or have previously received organ or allogeneic bone marrow transplants.
7. Ascites with clinical symptoms requiring paracentesis or drainage, or ascites that has been drained within the past 3 months. Excludes asymptomatic ascites with minimal amounts seen on imaging.
8. Uncontrolled hypertension despite antihypertensive medication (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg) (average of ≥2 measurements). Previous hypertension crisis or hypertensive encephalopathy.
9. Severe iodine contrast allergy that prevents TACE treatment.
10. HBV-DNA \&gt;2000 IU/ml (or 10\^4/ml); or HCV-RNA \&gt;10\^3/ml; or HBsAg+ anti-HCV antibody positive patients.
11. Coagulation dysfunction (International normalized ratio (INR) \&gt;2.0, Prothrombin time (PT) \&gt;16s), bleeding tendencies, or receiving thrombolytic or anticoagulant therapy. Preventive use of low-dose aspirin and low molecular weight heparin is allowed.
12. Arterial thromboembolism events within the past 6 months, such as cerebrovascular accidents (including transient ischemic attacks, intracerebral hemorrhage, cerebral infarction), or CTCAE grade 3 or higher deep vein thrombosis or pulmonary embolism.
13. Known hereditary or acquired bleeding and thrombosis disorders (e.g., hemophilia, coagulation disorders, thrombocytopenia).
14. Urinalysis indicating proteinuria ≥++ or 24-hour urine protein \&gt;1.0g.
15. Active infection, unexplained fever ≥38.5°C within 1 week before enrollment, or leukocyte count \&gt;15×10\^9/L during screening. Therapeutic antibiotics within 2 weeks before enrollment (excluding prophylactic antibiotics administered intravenously for ≤48 hours).
16. Congenital or acquired immunodeficiencies (e.g., HIV infection).
17. History of other malignancies within the past 3 years (except for cured basal cell carcinoma and cervical carcinoma in situ).
18. Uncontrolled cardiac symptoms or diseases, such as NYHA class II or higher heart failure, or echocardiography showing left ventricular ejection fraction (LVEF) \&lt;50%; unstable angina; myocardial infarction within the past year; significant clinical supraventricular or ventricular arrhythmias requiring treatment or intervention on ECG; QTc \&gt;450ms (male) or QTc \&gt;470ms (female) on resting ECG.
19. Palliative radiotherapy within 4 weeks before enrollment, with radiotherapy area exceeding 5% of bone marrow area in bone metastasis patients.
20. Major vascular events (e.g., aneurysms requiring surgical repair or recent peripheral arterial thrombosis) within 6 months before enrollment.
21. Administration of live vaccines within 4 weeks before the study drug or potential live vaccine administration during the study.
22. Previous treatment with other anti-PD-1 antibodies or other PD-1/PD-L1 targeted immunotherapy, or previous targeted therapy.
23. Pregnant, breastfeeding women, or women of childbearing age unwilling to use contraception.
24. Any other factors that may affect study results or lead to study discontinuation, as judged by the investigator, such as alcoholism, drug abuse, other severe diseases requiring concurrent treatment (including psychiatric disorders), severe laboratory abnormalities, or family or social factors affecting patient safety.
25. Severe, non-healing or open wounds, active ulcers, or untreated fractures.
26. Major surgery within 4 weeks before enrollment (excluding diagnostic procedures) or expected need for major surgery during the study.
27. Use of strong CYP3A4/CYP2C19 inducers (e.g., rifampicin and similar agents) or strong CYP3A4/CYP2C19 inhibitors within 14 days before enrollment.
28. Participation in other drug clinical trials within 4 weeks before enrollment.
29. Other factors that the investigator deems unsuitable for study participation.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: Generally, the ORR is assessed for each participant every two treatment cycles(each cycle is 3 weeks).
Secondary outcomes:
measure: Disease control rate (DCR)
timeFrame: Generally, the DCR is assessed for each participant every two treatment cycles(each cycle is 3 weeks).
measure: Duration of response (DoR)
timeFrame: Generally, the DoR is assessed for each participant every two treatment cycles(each cycle is 3 weeks).
measure: Progression-Free Survival (PFS)
timeFrame: Record the progression-freesurvival state of each participant at six months and twelve months after receiving the initial treatment.
measure: Overall Survival (OS)
timeFrame: Record the survival state of each participant at six months and twelve months after receiving the initial treatment.
Other outcomes:
measure: Number of peripheral blood lymphocytes
timeFrame: Peripheral blood lymphocyte will be conducted on Day 1±7 days before each of the first three cycles (each cycle is 3 weeks); thereafter, it will be checked every 6 weeks on Day 1±7 days until treatment end/withdrawal(no more than 12 months in total).
Locations:
city: Zhengzhou
country: China
facility: The Affiliated Cancer Hospital of Zhengzhou University &amp; Henan Cancer Hospital
state: Henan
Study officials:
name: Lin Zheng
role: PRINCIPAL_INVESTIGATOR
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