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

NCT05185531 | Unknown Phase 1

• 1 other identifier: Notable-HCC
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hepatocellular Carcinoma

Keywords

neoadjuvant; PD-1; stereotactic body radiotherapy, SBRT

Outcome Measures

Primary Outcomes (4)

• Delay to surgery

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

  Up to Day 92

• ORR after neoadjuvant SBRT+Tislelizumab

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

  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)

  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.

  2 months after resection

Secondary Outcomes (2)

• Disease-free survival disease-free survival (DFS)

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

• Overall survival

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

Study Arms (1)

Neoadjuvant

EXPERIMENTAL

PD-1(Tislelizumab) plus stereotactic body radiotherapy

Combination Product: PD-1 plus stereotactic body radiotherapy

Interventions

PD-1 plus stereotactic body radiotherapy COMBINATION_PRODUCT

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

Neoadjuvant

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1
• Adequate organ and marrow function as defined below:
• \) 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.
• \. 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.
• \. 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.
• \. 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.

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Shandong Cancer Hospital and Institute: lead
• BeiGene: collaborator

Study Sites (1)

Shandong Cancer Hospital and Institute

Jinan, Shandong, 250117, China

Location

Related Publications (2)

• 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.

  PMID: 36115673 BACKGROUND

• 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

  BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Radiosurgery

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

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Lei Zhao

  Shandong Cancer Hospital and Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 19, 2021
• First Posted: January 11, 2022
• Study Start: March 1, 2022
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: January 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)