CClinicalTrials.gg
Active, not recruitingNCT05185531Notable-HCCUpdated Jan 5, 2024

A Study of Neoadjuvant Tislelizumab With SBRT in Patients With Resectable Hepatocellular Carcinoma

A Phase 1 interventional study of PD-1 plus stereotactic body radiotherapy in Hepatocellular Carcinoma, sponsored by Shandong Cancer Hospital and Institute. Active, not recruiting at 1 site in China. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2024-01-05.

Sponsored by Shandong Cancer Hospital and Institute · Phase 1, Interventional, and Treatment

From the registry’s dates

  • Primary completion was expected by Dec 2024, 1 year 10 months ago, but the record still lists the study as active, not recruiting.
Phase
Phase 1
Study type
Interventional
Enrollment
20
Allocation
Not applicable
Ages
18 Years to 80 Years
Sex
All
01

Study summary

Notable-HCC is a phase Ib study of neoadjuvant stereotactic body radiotherapy (SBRT) plus Programmed cell death-1 (PD-1, Tislelizumab, BeiGene) prior to hepatic resection in patients with resectable HCC.

Read the detailed description

A baseline core tumor biopsy and peripheral venous blood will be collected from eligible participants at screening, and sample tumor tissue from the surgical specimen and PBMC (peripheral blood mononuclear cell) will be snap-frozen and stored for the future relevant studies.

Eligible patients will receive SBRT (8 Gy × 3 fractions, every other day) on day 1, day 3 and day 5; the first dose of Tislelizumab will be administrated concurrently on day 1, then the second on day 22 (the first day of week 4, ± 3 days). Then on day 50 (the first day of week 8, ± 7 days), curative liver resection of HCC will be scheduled.

Patients will be reviewed following completion of SBRT and tislelizumab treatment (Follow-up visit 1; FU1) prior to surgery.

Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) and HCC-Specific mRECIST criteria will be used to determine patient response to treatment, including CR (complete response), PR (partial response) and ORR (objective response rate). PBMC will be collected again and stored.

Hepatic resection will be performed as per standard of care. The safety FU2 will be conducted after the first dose of the post-resection tislelizumab. All AEs that occur prior to the visit will be recorded. Participants with on-going AEs at the visit will be followed up by principal investigator (PI) or delegate until resolution or stabilization of the event. Following FU2, participants will be assessed every 3 months (±7 days) thereafter to collect information regarding disease status and survival. Long-term follow-up will continue, for each patient, for a total of 5 years.

02

Conditions studied

  • Hepatocellular Carcinoma

Keywords

  • neoadjuvant
  • PD-1
  • stereotactic body radiotherapy, SBRT
03

In context

Carcinoma

6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.

This study's enrollment of 20 is below the median of 45 across 5,170 interventional studies indexed under Carcinoma.

Browse Carcinoma studies →

Lead sponsor

Shandong Cancer Hospital and Institute is the lead sponsor of 103 studies on the registry; 36 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Written informed consent for the trial.
  2. Aged ≥18 years
  3. Willing to provide tissue from an excisional biopsy of a tumor lesion
  4. Confirmed diagnosis of HCC. The diagnosis can be established radiographically by the criteria of the American Association for the Study of the Liver (AASLD), or by histologic diagnosis from the core biopsy.
  5. Have measurable disease by Computed Tomography (CT)-scan or Magnetic Resonance Imaging (MRI) defined by RECIST (Response Evaluation Criteria In Solid Tumours) 1.1 criteria and HCC specific mRECIST (modified RECIST).
  6. Medically fit to undergo surgery as determined by the treating medical and surgical oncology team
  7. ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1
  8. Adequate organ and marrow function as defined below:
  1. leukocytes ≥3,000/mcL 2) absolute neutrophil count ≥1,500/mcL 3) platelets ≥100,000/mcL 4) total bilirubin ≤ 2 × institutional upper limit of normal (ULN) 5) AST (aspartate aminotransferase)/ALT(alanine aminotransferase) ≤ 3 × institutional ULN 6) creatinine ≤ 1.5 × institutional ULN OR 7) estimated glomerular filtration rate (GFR) ≥50 mL/min/1.73 m2 (according to the Cockcroft-Gault formula) 9. Overall Child-Pugh class A 10. Documented virology status of hepatitis, as confirmed by screening tests for HBV (hepatitis B virus) and HCV (hepatitis C virus)
  1. For patients with active HBV: HBV DNA \<2000 IU/mL during screening, and have initiated anti-HBV treatment at least 14 days prior to SBRT and willingness to continue anti-HBV treatment during the study (per local standard of care; e.g., entecavir).
  2. Patients with HCV, either with resolved infection (as evidenced by detectable antibody and negative viral load) or chronic infection (as evidenced by detectable HCV RNA), are eligible.
  1. Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  1. Female patient of childbearing potential should have a negative serum pregnancy test within 24 h of her first dose of IMP (Investigational Medicinal Product) 13. Women of childbearing potential must be willing to use a highly effective method of contraception for the course of the study through 5 months after the last dose of IMP. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient.
  1. Sexually active males must agree to use an adequate method of contraception starting with the first dose of IMP through 7 months after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient.

Exclusion criteria

Exclusion Criteria:

  1. Extrahepatic metastasis
  2. Prior systemic anticancer treatment for HCC, including an anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibody
  3. Prior orthotopic liver transplantation
  4. Prior abdominal irradiation
  5. Any major surgery within the 3 weeks prior to enrolment
  6. Hepatic encephalopathy
  7. Ascites that is refractory to diuretic therapy
  8. Is currently receiving anti-cancer therapy (chemotherapy, radiation therapy, immunotherapy or biologic therapy) or has participated or is participating in a study of an IMP or used an investigational device within 4 weeks of the first dose of IMP
  9. Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy
  10. Known history of active Bacillus Tuberculosis (TB)
  11. History of known hypersensitivity to any monoclonal antibody or any of their excipients
  12. Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer
  13. Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  14. Active infection requiring systemic therapy, with exceptions relating to Hepatitis B and C virus infection
  15. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating Principal Investigator (PI)
  16. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  17. Pregnant or breastfeeding
  18. Known history of Human Immunodeficiency Virus (HIV; HIV 1/2 antibodies)
  19. Received a live vaccine within 30 days of first dose of IMP administration.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
20 participants (actual)

Study arms

  • Experimental
    Neoadjuvant

    PD-1(Tislelizumab) plus stereotactic body radiotherapy

    Combination Product: PD-1 plus stereotactic body radiotherapy

Interventions

  • Combination productPD-1 plus stereotactic body radiotherapy

    neoadjuvant PD-1(Tislelizumab) plus stereotactic body radiotherapy (8 Gy × 3 fractions) in resectable HCC

06

What researchers measure

Primary outcomes

  1. Delay to surgery

    number of patients experiencing a surgery delay over 6 weeks or later

    Time frame: Up to Day 92

  2. ORR after neoadjuvant SBRT+Tislelizumab

    ORR on pre-resection imaging according to the RECIST v1.1/ mRECIST criteria

    Time frame: One day before resection

  3. Pathologic response rate on evaluation of the resected specimen

    pCR (pathological complete response), pPR (pathological partial response), MPR (major pathologic response)

    Time frame: One month after resection

  4. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

    Safety and tolerability of the sequential SBRT/tislelizumab based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 criteria, including all grade irAEs (Immune-related adverse events) and irAE of grade 3/4.

    Time frame: 2 months after resection

Secondary outcomes

  1. Disease-free survival disease-free survival (DFS)

    DFS (disease-free survival) after successful curative resection of tumor

    Time frame: From date of resection until the date of first documented progression, assessed up to 3 years

  2. Overall survival

    OS (overall survival) after successful curative resection of tumor

    Time frame: From date of resection until the date of death from any cause, assessed up to 5 years

07

Study locations

1 site
  • Shandong Cancer Hospital and Institute
    Jinan, Shandong 250117, China
08

References and documents

Publications

  • Zhang B, Yue J, Shi X, Cui K, Li L, Zhang C, Sun P, Zhong J, Li Z, Zhao L. Protocol of notable-HCC: a phase Ib study of neoadjuvant tislelizumab with stereotactic body radiotherapy in patients with resectable hepatocellular carcinoma. BMJ Open. 2022 Sep 17;12(9):e060955. doi: 10.1136/bmjopen-2022-060955. PubMed 36115673 ↗
  • Li M, Yue J, Zhang B, Shi X, Cui K, Liu J, Li Z, Zhao L. Interim report of Notable-HCC: a phase Ⅰb study of neoadjuvant PD-1 with stereotactic body radiotherapy in patients with resectable HCC[J]. Annals of Oncology. VOLUME 34, SUPPLEMENT 2, S598-S599, OCTOBER 2023

Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 5, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05185531
Lead sponsor
Shandong Cancer Hospital and Institute
Collaborators
BeiGene
Responsible party
Lei ZHAO (Professor, Shandong Cancer Hospital and Institute) — Principal investigator
First posted
Jan 11, 2022
Start date
Mar 1, 2022
Primary completion
Dec 2024 (estimated)
Completion
Dec 2024 (estimated)
Last update
Jan 5, 2024

Study contacts

Lei Zhao
principal investigator · Shandong Cancer Hospital and Institute

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Jan 2024. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion