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.
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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
neoadjuvant PD-1(Tislelizumab) plus stereotactic body radiotherapy (8 Gy × 3 fractions) in resectable HCC
Shandong Cancer Hospital and Institute
Jinan, Shandong, China
Delay to surgery
number of patients experiencing a surgery delay over 6 weeks or later
Time frame: Up to Day 92
ORR after neoadjuvant SBRT+Tislelizumab
ORR on pre-resection imaging according to the RECIST v1.1/ mRECIST criteria
Time frame: 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)
Time frame: 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.
Time frame: 2 months after resection
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
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
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