Hepatocellular CarcinomaPhase 1Notable-HCCNCT05185531
A Study of Neoadjuvant Tislelizumab With SBRT in Patients With Resectable Hepatocellular Carcinoma
A Phase 1 study testing PD-1 plus stereotactic body radiotherapy in people with Hepatocellular Carcinoma, run by Shandong Cancer Hospital and Institute at 1 site in China.
Trial 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 more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- PD-1 plus stereotactic body radiotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 1 Mar 2022to Dec 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent for the trial.
- Aged ≥18 years
- Willing to provide tissue from an excisional biopsy of a tumor lesion
- 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.
- 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).
- Medically fit to undergo surgery as determined by the treating medical and surgical oncology team
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- ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1
- 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)
- 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).
- 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.
- 11. 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.
- 12. 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.
- 14. 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.
Who cannot join
- Extrahepatic metastasis
- Prior systemic anticancer treatment for HCC, including an anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibody
- Prior orthotopic liver transplantation
- Prior abdominal irradiation
- Any major surgery within the 3 weeks prior to enrolment
- Hepatic encephalopathy
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- Ascites that is refractory to diuretic therapy
- 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
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy
- Known history of active Bacillus Tuberculosis (TB)
- History of known hypersensitivity to any monoclonal antibody or any of their excipients
- 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
- 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
- Active infection requiring systemic therapy, with exceptions relating to Hepatitis B and C virus infection
- 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)
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Pregnant or breastfeeding
- Known history of Human Immunodeficiency Virus (HIV; HIV 1/2 antibodies)
- Received a live vaccine within 30 days of first dose of IMP administration.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase Ib Study of Neoadjuvant Tislelizumab With Stereotactic Body Radiotherapy in Patients With Resectable Hepatocellular Carcinoma
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.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- PD-1 plus stereotactic body radiotherapy
- Keywords
- neoadjuvant, PD-1, stereotactic body radiotherapy, SBRT
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD-1 plus stereotactic body radiotherapyCombination product
neoadjuvant PD-1(Tislelizumab) plus stereotactic body radiotherapy (8 Gy × 3 fractions) in resectable HCC
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant | Experimental | PD-1(Tislelizumab) plus stereotactic body radiotherapy Receives: Combination Product: PD-1 plus stereotactic body radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Delay to surgery
number of patients experiencing a surgery delay over 6 weeks or later
Measured: Up to Day 92
ORR after neoadjuvant SBRT+Tislelizumab
ORR on pre-resection imaging according to the RECIST v1.1/ mRECIST criteria
Measured: One day before resection
Pathologic response rate on evaluation of the resected specimen
pCR (pathological complete response), pPR (pathological partial response), MPR (major pathologic response)
Measured: One month after resection
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.
Measured: 2 months after resection
Secondary outcomes (2)
Disease-free survival disease-free survival (DFS)
DFS (disease-free survival) after successful curative resection of tumor
Measured: From date of resection until the date of first documented progression, assessed up to 3 years
Overall survival
OS (overall survival) after successful curative resection of tumor
Measured: From date of resection until the date of death from any cause, assessed up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2022
- Study start1 Mar 2022
- Primary completionDec 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shandong Cancer Hospital and Institute
- Sponsor type
- University, hospital or other
- Collaborators
- BeiGene
- Responsible party
- Principal investigator, Lei ZHAO, Shandong Cancer Hospital and Institute
- Investigators
- Lei Zhao, Principal investigator, Shandong Cancer Hospital and Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05185531
- Sponsor's protocol ID
- Notable-HCC
- Acronym
- Notable-HCC
- Status last verified
- Jan 2024
- First submitted
- 19 Dec 2021
- Last updated
- 5 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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 36115673Li 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
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Study of Neoadjuvant Tislelizumab With Stereotactic Body Radiotherapy in Patients With Resectable Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT05185531
- Acronym / sponsor ID
- Notable-HCC / Notable-HCC
- Conditions
- Hepatocellular Carcinoma
- Keywords
- neoadjuvant, PD-1, stereotactic body radiotherapy, SBRT
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Shandong Cancer Hospital and InstituteUniversity, hospital or other
- Collaborators
- BeiGene
- Study start
- 1 Mar 2022 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 11 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant | Experimental | Combination Product: PD-1 plus stereotactic body radiotherapyPD-1(Tislelizumab) plus stereotactic body radiotherapy |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Written informed consent for the trial.
- Aged ≥18 years
- Willing to provide tissue from an excisional biopsy of a tumor lesion
- 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.
- 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).
Key exclusion criteria (19 listed)
- Extrahepatic metastasis
- Prior systemic anticancer treatment for HCC, including an anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibody
- Prior orthotopic liver transplantation
- Prior abdominal irradiation
- Any major surgery within the 3 weeks prior to enrolment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PD-1 plus stereotactic body radiotherapyneoadjuvant PD-1(Tislelizumab) plus stereotactic body radiotherapy (8 Gy × 3 fractions) in resectable HCC | Combination product | Neoadjuvant |
Primary outcome
Delay to surgery
Time frame: Up to Day 92
number of patients experiencing a surgery delay over 6 weeks or later
ORR after neoadjuvant SBRT+Tislelizumab
Time frame: One day before resection
ORR on pre-resection imaging according to the RECIST v1.1/ mRECIST criteria
Pathologic response rate on evaluation of the resected specimen
Time frame: One month after resection
pCR (pathological complete response), pPR (pathological partial response), MPR (major pathologic response)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: 2 months after resection
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.
2 secondary outcomes
Disease-free survival disease-free survival (DFS)
Time frame: From date of resection until the date of first documented progression, assessed up to 3 years
Overall survival
Time frame: From date of resection until the date of death from any cause, assessed up to 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2024.
- Background: PubMed 36115673Zhang 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.
- BackgroundLi 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 dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lei Zhao principal investigator
Shandong Cancer Hospital and Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PD-1 plus stereotactic body radiotherapy in people with Hepatocellular Carcinoma, run by Shandong Cancer Hospital and Institute at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Delay to surgery (time frame: Up to Day 92). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05185531, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2024.