Sequential T and I With H101 Via HAI for BCLC C Stage HCC: A Prospective Single-Center Single-Arm Pilot Study

NCT06685354 | Not Yet Recruiting Phase 2

• 1 other identifier: 2024-281-002
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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\' 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.

Conditions

Hepatocellular Carcinoma (HCC)

Outcome Measures

Primary Outcomes (1)

• 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.

  Generally, the ORR is assessed for each participant every two treatment cycles(each cycle is 3 weeks).

Secondary Outcomes (4)

• Disease control rate (DCR)

  Generally, the DCR is assessed for each participant every two treatment cycles(each cycle is 3 weeks).

• Duration of response (DoR)

  Generally, the DoR is assessed for each participant every two treatment cycles(each cycle is 3 weeks).

• Progression-Free Survival (PFS)

  Record the progression-freesurvival state of each participant at six months and twelve months after receiving the initial treatment.

• Overall Survival (OS)

  Record the survival state of each participant at six months and twelve months after receiving the initial treatment.

Other Outcomes (1)

• Number of peripheral blood lymphocytes

  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).

Study Arms (1)

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.

Drug: hepatic arterial infusion of recombinant human type 5 adenovirus

Interventions

hepatic arterial infusion of recombinant human type 5 adenovirus DRUG

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.

experimental group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Henan Cancer Hospital: lead

Study Sites (1)

The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital

Zhengzhou, Henan, 450003, China

Location

Related Publications (17)

• 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.

  PMID: 7701146 RESULT

• Marshall 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.

  PMID: 10636774 RESULT

• Yi 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.

  PMID: 38325225 RESULT

• Lin 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.

  PMID: 26470869 RESULT

• Sivanandam 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.

  PMID: 31080879 RESULT

• Ribas 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.

  PMID: 28886381 RESULT

• Sharma 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.

  PMID: 28187290 RESULT

• Qin 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.

  PMID: 37499670 RESULT

• Ren 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.

  PMID: 34143971 RESULT

• Galle 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.

  PMID: 34051880 RESULT

• Tian 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.

  PMID: 28371798 RESULT

• Finn 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.

  PMID: 32402160 RESULT

• Finn 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.

  PMID: 32716739 RESULT

• Forner 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.

  PMID: 29307467 RESULT

• Villanueva A. Hepatocellular Carcinoma. N Engl J Med. 2019 Apr 11;380(15):1450-1462. doi: 10.1056/NEJMra1713263. No abstract available.

  PMID: 30970190 RESULT

• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.

  PMID: 30207593 RESULT

• Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol. 2019 Oct;16(10):589-604. doi: 10.1038/s41575-019-0186-y. Epub 2019 Aug 22.

  PMID: 31439937 RESULT

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Lin Zheng

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lin Zheng

CONTACT

+86 15838162655; hyzhenglin@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2024
• First Posted: November 12, 2024
• Study Start: November 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: November 12, 2024

Record last verified: 2024-06

Locations

CN (1)