This study is a prospective phase II, single arm clinical study conducted in Queen Mary Hospital (Hong Kong) assessing the efficacy and safety of the sequential administration of trans-arterial chemo-embolization (TACE) and stereotactic body radiotherapy (SBRT) with an immune checkpoint inhibitor in hepatocellular carcinoma (HCC) patients.
All the patients must be registered with the Investigator(s) prior to initiation of treatment. The registration desk will confirm all eligibility criteria and obtain essential information (including patient number). TACE should start within 28 days of study registration and its procedure will be standardised. SBRT screening and planning will be performed by radiation therapists, medical physicists, and oncologists.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
33
Procedure of TACE will be standardized.
SBRT screening and planning will be performed by radiation therapists, medical physicists, and oncologists.
An immune checkpoint inhibitor may be administered up to 3 days before or after the scheduled day of administration of each cycle due to administrative reasons.
Department of Clinical Oncology
Hong Kong, Hong Kong
Number of Patients Amendable to Curative Surgical Interventions
Number of patients amendable to curative surgical interventions defined as number of patients receiving curative surgical resection or transplantation after successful down-sizing of tumor(s) by intervention.
Time frame: from the date of first study treatment to the date of last study treatment, an average of 3 years
Response rate measured by mRECIST criteria
Complete response (CR): Disappearance of any intra-tumoral arterial enhancement in all target lesions Partial response (PR): At least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions Stable disease (SD): Any cases that do not qualify for either partial response or progressive disease Progressive disease (PD): An increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since treatment started
Time frame: from the date of screening to radiographically documented progression according to mRECIST 1.1, assessed up to 3 years
Time to progression (TTP)
Time to progression (TTP): measured from the date of first study treatment to radiographically documented progression according to mRECIST 1.1. This does not include death from any cause.
Time frame: from the date of first study treatment to radiographically documented progression according to mRECIST 1.1, assessed up to 3 years
Progression-free survival (PFS)
Progression-free survival (PFS): measured from the date of first study treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause (whichever occurs first). Participants alive and without disease progression or lost to follow-up will be censored at the date of their last radiographic assessment.
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Time frame: from the date of first study treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause, whichever occurs first, assessed up to 3 years
Overall survival (OS)
Overall survival (OS): measured from date of first study treatment to the date of death from any cause. Participants alive or lost to follow-up will be censored at the date of their last visit.
Time frame: from the date of first study treatment to the date of death from any cause, assessed up to 5 years
European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30) Score
Quality-of-Life (QoL) is assessed by the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30).
Time frame: from the date of screening to radiographically documented progression according to mRECIST 1.1, an average of 3 years
Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) Score
Quality-of-Life (QoL) is also assessed by the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaires.
Time frame: from the date of screening to radiographically documented progression according to mRECIST 1.1, an average of 3 years
Incidence of Study-Related Adverse Events [Safety and Tolerability]
Incidence, nature, and severity of adverse events graded according to the United States National Cancer Institute The Common Terminology Criteria for Adverse Events (NCI CTCAE 4.0)
Time frame: from the date of screening to 90 days after last treatment, around 3 years and 90 days
Pathological response
Pathological response is assessed as the percentage of surface with non-viable cancer cells (represented by necrosis or fibrosis, the ultimate stage of necrosis) in relation to the total tumor area and will be equal to: 100% - viable cancer cells (%). If there are multiple tumors, the mean percentage will be used. Pathological complete response (pCR) is defined by the absence of viable tumor cells in any nodule.
Time frame: from the date of first study treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause, whichever occurs first, assessed up to 5 years
Disease control rate
Percentage of patients that had a CR, PR, or SD ≥ 6 months per mRECIST
Time frame: from the date of first study treatment to radiographically documented response according to mRECIST 1.1, assessed up to 3 years
Local control
Defined as absence of recurrence within the high-dose region (80% isodose volume), demonstrated by new enhancement or mRECIST progressive disease
Time frame: from the date of first study treatment to radiographically documented in-field progression according to mRECIST 1.1, censored at the time of intervention to target lesion, assessed up to 3 years
Duration of response
Defined as the time from first documented evidence of CR or PR until the first documented sign of disease progression (PD) or death from any cause
Time frame: from the date of first documented evidence of CR or PR to first documented sign of PD or death from any cause according to mRECIST 1.1, assessed up to 3 years
Pattern of failure
(1) In-field failure: defined as recurrence within the high-dose region (80% iso-dose volume), demonstrated by new enhancement or mRECIST progressive disease; (2) Out-field (intra-hepatic): defined as new or mRECIST progressive disease within liver parenchyma, but outside the SBRT treated volume; (3) New vascular invasion: defined as new portal or hepatic vein invasion; (4) Distant failure: defined as new disease outside liver parenchyma
Time frame: from the date of first study treatment to radiographically documented failure type according to mRECIST 1.1, assessed up to 3 years