Hepatocellular Carcinoma (HCC)Phase 2NCT06685354
Sequential T and I With H101 Via HAI for BCLC C Stage HCC: A Prospective Single-Center Single-Arm Pilot Study
A Phase 2 study testing hepatic arterial infusion of recombinant human type 5 adenovirus in people with Hepatocellular Carcinoma (HCC), run by Henan Cancer Hospital at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma (HCC)
- What is being tested?
- hepatic arterial infusion of recombinant human type 5 adenovirus
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteChina
- Study dates
- Nov 2024to Oct 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Voluntarily participating in the study, signing the informed consent form, and willing to undergo follow-up;
- Age ≥ 18 years and ≤ 75 years, regardless of gender;
- Clinically or pathologically confirmed BCLC Stage C hepatocellular carcinoma, with no prior TACE or systemic treatment;
- Baseline imaging (MRI or CT) showing measurable lesions with a longest diameter ≥ 1 cm;
- Child-Pugh score ≤ 7 (Child-Pugh A-B);
- Liver tumor burden not exceeding 50% of the liver volume;
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- Able to swallow pills normally;
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1 (see Appendix 1 for ECOG PS scoring);
- Expected survival ≥ 3 months;
- 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 \> 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;
- 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;
- 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.
Who cannot join
- 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.
- 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.
- Use of immunosuppressants or systemic steroids within 2 weeks before enrollment for immunosuppressive purposes (dose \>10mg/day of prednisone or equivalent).
- Allergy to any monoclonal antibodies, anti-angiogenesis targeted drugs, or excipients.
- Known history of central nervous system metastases or hepatic encephalopathy.
- Patients who are preparing for or have previously received organ or allogeneic bone marrow transplants.
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- 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.
- Uncontrolled hypertension despite antihypertensive medication (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg) (average of ≥2 measurements). Previous hypertension crisis or hypertensive encephalopathy.
- Severe iodine contrast allergy that prevents TACE treatment.
- HBV-DNA \>2000 IU/ml (or 10^4/ml); or HCV-RNA \>10^3/ml; or HBsAg+ anti-HCV antibody positive patients.
- Coagulation dysfunction (International normalized ratio (INR) \>2.0, Prothrombin time (PT) \>16s), bleeding tendencies, or receiving thrombolytic or anticoagulant therapy. Preventive use of low-dose aspirin and low molecular weight heparin is allowed.
- 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.
- Known hereditary or acquired bleeding and thrombosis disorders (e.g., hemophilia, coagulation disorders, thrombocytopenia).
- Urinalysis indicating proteinuria ≥++ or 24-hour urine protein \>1.0g.
- Active infection, unexplained fever ≥38.5°C within 1 week before enrollment, or leukocyte count \>15×10^9/L during screening. Therapeutic antibiotics within 2 weeks before enrollment (excluding prophylactic antibiotics administered intravenously for ≤48 hours).
- Congenital or acquired immunodeficiencies (e.g., HIV infection).
- History of other malignancies within the past 3 years (except for cured basal cell carcinoma and cervical carcinoma in situ).
- Uncontrolled cardiac symptoms or diseases, such as NYHA class II or higher heart failure, or echocardiography showing left ventricular ejection fraction (LVEF) \<50%; unstable angina; myocardial infarction within the past year; significant clinical supraventricular or ventricular arrhythmias requiring treatment or intervention on ECG; QTc \>450ms (male) or QTc \>470ms (female) on resting ECG.
- Palliative radiotherapy within 4 weeks before enrollment, with radiotherapy area exceeding 5% of bone marrow area in bone metastasis patients.
- Major vascular events (e.g., aneurysms requiring surgical repair or recent peripheral arterial thrombosis) within 6 months before enrollment.
- Administration of live vaccines within 4 weeks before the study drug or potential live vaccine administration during the study.
- Previous treatment with other anti-PD-1 antibodies or other PD-1/PD-L1 targeted immunotherapy, or previous targeted therapy.
- Pregnant, breastfeeding women, or women of childbearing age unwilling to use contraception.
- 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.
- Severe, non-healing or open wounds, active ulcers, or untreated fractures.
- Major surgery within 4 weeks before enrollment (excluding diagnostic procedures) or expected need for major surgery during the study.
- Use of strong CYP3A4/CYP2C19 inducers (e.g., rifampicin and similar agents) or strong CYP3A4/CYP2C19 inhibitors within 14 days before enrollment.
- Participation in other drug clinical trials within 4 weeks before enrollment.
- Other factors that the investigator deems unsuitable for study participation.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital
Zhengzhou, Henan, 450003
Lin Zheng, +86 15838162655, hyzhenglin@163.com
Yao Chen, +86 16692179977, chenyao9021@163.com
About this 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
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\' immune systems before and after treatment, providing a basis for formal research.
Read more
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.
- Conditions
- Hepatocellular Carcinoma (HCC)
- Being tested
- hepatic arterial infusion of recombinant human type 5 adenovirus
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hepatic arterial infusion of recombinant human type 5 adenovirusDrug
Participants will receive hepatic arterial infusion of recombinant human type 5 adenovirus (H101). The H101 treatment regimen consists of 3 cycles or until a specific treatment discontinuation event occurs as outlined in the protocol. The H101 administration method is as follows: if the sum of the largest diameters of lesions is ≤10 cm, the total dose is 1.0×10^12 vp (2 vials); if the sum of the largest diameters is \>10 cm, the total dose is 1.5×10^12 vp (3 vials). Treatment cycles are every 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| experimental group | Experimental | The participants will receive hepatic arterial infusion of recombinant human adenovirus type 5 injection in combination with first-line targeted and immunotherapy as recommended by the 2024 primary liver cancer treatment guidelines. Receives: Drug: hepatic arterial infusion of recombinant human type 5 adenovirus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR)
The ORR is defined as the proportion of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) according to RECIST 1.1 criteria.
Measured: Generally, the ORR is assessed for each participant every two treatment cycles(each cycle is 3 weeks).
Secondary outcomes (4)
Disease control rate (DCR)
The percentage of participants who achieve a BOR of CR, PR, or SD lasting at least 6 weeks, assessed according to RECIST 1.1 and mRECIST criteria.
Measured: Generally, the DCR is assessed for each participant every two treatment cycles(each cycle is 3 weeks).
Duration of response (DoR)
DoR is defined as the time from the first recorded objective response (assessed according to RECIST 1.1 and mRECIST criteria) to the first recorded progression of target tumors (assessed according to RECIST 1.1 or mRECIST criteria) or to the date of any earlier death for any reason.
Measured: Generally, the DoR is assessed for each participant every two treatment cycles(each cycle is 3 weeks).
Progression-Free Survival (PFS)
PFS is defined as the time from the first study treatment date to the first recorded tumor progression (according to RECIST 1.1 or mRECIST criteria, regardless of whether the study is still ongoing) or to the time of any earlier death for any reason.
Measured: Record the progression-freesurvival state of each participant at six months and twelve months after receiving the initial treatment.
Overall Survival (OS)
OS is defined as the time from the first study treatment date to death from any cause.
Measured: Record the survival state of each participant at six months and twelve months after receiving the initial treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2024
- Study startNov 2024 (estimated)
- Primary completionOct 2026 (estimated)
- Study completionOct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular Carcinoma (HCC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Henan Cancer Hospital
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Lin Zheng, Principal investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06685354
- Sponsor's protocol ID
- 2024-281-002
- Status last verified
- Jun 2024
- First submitted
- 7 Nov 2024
- Last updated
- 12 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Birkett MA, Day SJ. Internal pilot studies for estimating sample size. Stat Med. 1994 Dec 15-30;13(23-24):2455-63. doi: 10.1002/sim.4780132309.
PubMed 7701146Marshall E. Gene therapy death prompts review of adenovirus vector. Science. 1999 Dec 17;286(5448):2244-5. doi: 10.1126/science.286.5448.2244. No abstract available.
PubMed 10636774Yi L, Ning Z, Xu L, Shen Y, Zhu X, Yu W, Xie J, Meng Z. The combination treatment of oncolytic adenovirus H101 with nivolumab for refractory advanced hepatocellular carcinoma: an open-label, single-arm, pilot study. ESMO Open. 2024 Feb;9(2):102239. doi: 10.1016/j.esmoop.2024.102239. Epub 2024 Feb 6.
PubMed 38325225Lin XJ, Li QJ, Lao XM, Yang H, Li SP. Transarterial injection of recombinant human type-5 adenovirus H101 in combination with transarterial chemoembolization (TACE) improves overall and progressive-free survival in unresectable hepatocellular carcinoma (HCC). BMC Cancer. 2015 Oct 15;15:707. doi: 10.1186/s12885-015-1715-x.
PubMed 26470869Sivanandam V, LaRocca CJ, Chen NG, Fong Y, Warner SG. Oncolytic Viruses and Immune Checkpoint Inhibition: The Best of Both Worlds. Mol Ther Oncolytics. 2019 Apr 25;13:93-106. doi: 10.1016/j.omto.2019.04.003. eCollection 2019 Jun 28.
PubMed 31080879Ribas A, Dummer R, Puzanov I, VanderWalde A, Andtbacka RHI, Michielin O, Olszanski AJ, Malvehy J, Cebon J, Fernandez E, Kirkwood JM, Gajewski TF, Chen L, Gorski KS, Anderson AA, Diede SJ, Lassman ME, Gansert J, Hodi FS, Long GV. Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy. Cell. 2017 Sep 7;170(6):1109-1119.e10. doi: 10.1016/j.cell.2017.08.027.
PubMed 28886381Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A. Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. Cell. 2017 Feb 9;168(4):707-723. doi: 10.1016/j.cell.2017.01.017.
PubMed 28187290Qin S, Chan SL, Gu S, Bai Y, Ren Z, Lin X, Chen Z, Jia W, Jin Y, Guo Y, Hu X, Meng Z, Liang J, Cheng Y, Xiong J, Ren H, Yang F, Li W, Chen Y, Zeng Y, Sultanbaev A, Pazgan-Simon M, Pisetska M, Melisi D, Ponomarenko D, Osypchuk Y, Sinielnikov I, Yang TS, Liang X, Chen C, Wang L, Cheng AL, Kaseb A, Vogel A; CARES-310 Study Group. Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study. Lancet. 2023 Sep 30;402(10408):1133-1146. doi: 10.1016/S0140-6736(23)00961-3. Epub 2023 Jul 24.
PubMed 37499670Ren Z, Xu J, Bai Y, Xu A, Cang S, Du C, Li Q, Lu Y, Chen Y, Guo Y, Chen Z, Liu B, Jia W, Wu J, Wang J, Shao G, Zhang B, Shan Y, Meng Z, Wu J, Gu S, Yang W, Liu C, Shi X, Gao Z, Yin T, Cui J, Huang M, Xing B, Mao Y, Teng G, Qin Y, Wang J, Xia F, Yin G, Yang Y, Chen M, Wang Y, Zhou H, Fan J; ORIENT-32 study group. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study. Lancet Oncol. 2021 Jul;22(7):977-990. doi: 10.1016/S1470-2045(21)00252-7. Epub 2021 Jun 15.
PubMed 34143971Galle PR, Finn RS, Qin S, Ikeda M, Zhu AX, Kim TY, Kudo M, Breder V, Merle P, Kaseb A, Li D, Mulla S, Verret W, Xu DZ, Hernandez S, Ding B, Liu J, Huang C, Lim HY, Cheng AL, Ducreux M. Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Jul;22(7):991-1001. doi: 10.1016/S1470-2045(21)00151-0. Epub 2021 May 27.
PubMed 34051880Tian L, Goldstein A, Wang H, Ching Lo H, Sun Kim I, Welte T, Sheng K, Dobrolecki LE, Zhang X, Putluri N, Phung TL, Mani SA, Stossi F, Sreekumar A, Mancini MA, Decker WK, Zong C, Lewis MT, Zhang XH. Mutual regulation of tumour vessel normalization and immunostimulatory reprogramming. Nature. 2017 Apr 13;544(7649):250-254. doi: 10.1038/nature21724. Epub 2017 Apr 3.
PubMed 28371798Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL; IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894-1905. doi: 10.1056/NEJMoa1915745.
PubMed 32402160Finn RS, Ikeda M, Zhu AX, Sung MW, Baron AD, Kudo M, Okusaka T, Kobayashi M, Kumada H, Kaneko S, Pracht M, Mamontov K, Meyer T, Kubota T, Dutcus CE, Saito K, Siegel AB, Dubrovsky L, Mody K, Llovet JM. Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma. J Clin Oncol. 2020 Sep 10;38(26):2960-2970. doi: 10.1200/JCO.20.00808. Epub 2020 Jul 27.
PubMed 32716739Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018 Mar 31;391(10127):1301-1314. doi: 10.1016/S0140-6736(18)30010-2. Epub 2018 Jan 5.
PubMed 29307467Villanueva A. Hepatocellular Carcinoma. N Engl J Med. 2019 Apr 11;380(15):1450-1462. doi: 10.1056/NEJMra1713263. No abstract available.
PubMed 30970190