Advanced Hepatocellular CarcinomaPhase 2NCT04183088
Regorafenib Plus Tislelizumab as First-line Systemic Therapy for Patients With Advanced Hepatocellular Carcinoma
A Phase 2 study testing Tislelizumab+regorafenib for part 1;Tislelizumab+regorafenib for group 1 of part 2; Regorafenib for group 2 of part 2. in people with Advanced Hepatocellular Carcinoma, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
Combination of anti-angiogenic molecular targeted therapy and anti- programmed cell death -1 immune checkpoint inhibitor (ICI) therapy has shown promising antitumor activity in multiple cancer types, including patients with advanced hepatocellular carcinoma (HCC). Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Advanced Hepatocellular Carcinoma
- What is being tested?
- Tislelizumab+regorafenib for part 1;Tislelizumab+regorafenib for group 1 of part 2; Regorafenib for group 2 of part 2.
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 125 participants
- Where
- 1 siteTaiwan
- Study dates
- 16 Dec 2020to 1 Mar 2025
- Phase
- Phase 2
- 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments
- Age ≥ 20 years, according to local regulation in Taiwan, at time of signing Informed Consent Form.
- Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology.
- Disease that is not amenable to curative surgical and/or locoregional therapies, or progressive disease after surgical and /or locoregional therapies
- Agreement to have a new tumor biopsy for eligibility to this study
- No prior systemic therapy (including systemic investigational agents) for HCC.
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- For patients with chronic hepatitis B virus (HBV) infection: agreement to receive anti-HBV treatment (per local standard of care; e.g., entecavir) prior to study entry and willingness to continue treatment for the length of the study.
- At least one measurable (per RECIST 1.1) lesion. Patients who received prior local therapy (e.g., radiofrequency ablation or transarterial chemoembolization, etc.) are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST version 1.1.
- The liver tumors, if any, should occupy ≤ 50% of estimated liver volume.
- Eastern Cooperative Oncology Group Performance Status of 0 or 1 within 7 days prior to first dose of study drug treatment.
- Child-Pugh class A within 14 days prior to first dose of study drug treatment.
- Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 7 days prior to first dose of study drug treatment, unless otherwise specified:
- Absolute neutrophil count≥1.5 * 109/L without granulocyte colony-stimulating factor support; platelet count ≥75 *109/L without transfusion; and hemoglobin≥(9 g/dL (patients may be transfused to meet this criterion).
- Liver transaminases (AST and ALT) ≤5 x upper limit of normal (ULN)
- Serum creatinine ≤1.5 x ULN or creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault formula)
- Urine dipstick for proteinuria < 2+ (within 7 days prior to initiation of study treatment). Patients who have ≥ 2+ proteinuria on dipstick urinalysis at baseline will be eligible if he/she have daily protein excretion of < 1 g documented by a 24-hour urine collection.
- Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, ≥ 8 weeks after the last dose of regorafenib, and ≥ 120 days after the last dose of tislelizumab, and have a negative urine or serum pregnancy test ≤ 7 days of first dose of study drug treatment.
- Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study, ≥ 8 weeks after the last dose of regorafenib, and ≥ 120 days after the last dose of tislelizumab
Who cannot join
- Histological diagnosis of fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
- Liver tumor(s) with main portal vein thrombosis.
- Known human immunodeficiency virus (HIV) infection.
- History of esophageal/gastric varices or active peptic ulcers that are considered to have high risk of bleeding.
- History of upper gastrointestinal bleeding within 1 year.
- Underlying medical conditions that, in the investigator's opinion, will render the administration of study drug hazardous or obscure the interpretation of toxicity or AEs."
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- Prior allogeneic stem cell or solid organ transplantation.
- Treatment with investigational therapy within 28 days prior to initiation of study treatment.
- Prior therapy with an anti-Programmed cell death protein(PD)-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte protein 4 antibody (or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways).
- Local therapy to liver (e.g., radiofrequency ablation, transarterial chemoembolization, etc.) within 28 days prior to initiation of study treatment or non-recovery from side effects of any such procedure.
- Radiotherapy within 28 days and abdominal/ pelvic radiotherapy within 60 days prior to initiation of study treatment, except for palliative radiotherapy to bone lesions. Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period.
- Patients with a history of treated and, at the time of screening, asymptomatic central nervous system(CNS) metastases are eligible, provided they meet all the following:
- Brain imaging at screening shows no evidence of interim progression
- Have measurable disease outside the CNS
- No ongoing requirement for corticosteroids as therapy for CNS disease; anticonvulsants at a stable dose allowed
- No stereotactic radiation or whole-brain radiation within 14 days prior to randomization,
- Patients with new asymptomatic CNS metastases detected at the screening scan must receive radiation therapy and/or surgery for CNS metastases.
- Following treatment, these patients may then be eligible, provided all other criteria, including those for patients with a history of brain metastases, are met.
- Active autoimmune diseases or history of autoimmune diseases that may relapse. Patients with the following diseases are not excluded and may proceed to further screening: vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
- History of drug-induced pneumonitis or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
- Known active tuberculosis or other active infection.
- Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment. Core biopsy or other minor surgical procedure within 3 days prior to the first dose of regorafenib.
- History of malignancy other than HCC within 3 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival(OS) rate> 90%), such as adequately treated carcinoma in situ of the cervix, non melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or stage I uterine cancer.
- Requirement of systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses ≤ 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Short course (≤ 7 days) of corticosteroid prescribed prophylactically (eg, for contrast dye allergy) or for the treatment of a non-autoimmune condition (eg, delayed-type hypersensitivity reaction caused by contact allergen) may be allowed.
- Current or recent (within 10 days of first dose of study treatment) use of aspirin (>325 mg/day), other anti-platelet therapy (e.g., dipyramidole, ticlopidine, clopidogrel, and cilostazol), or full dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose.
- History of abdominal or tracheoesophageal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months prior to initiation of study treatment.
- Uncontrolled hypertension: systolic pressure ≥ 160 mmHg or diastolic pressure ≥ 100 mmHg despite anti-hypertension medications ≤ 28 days before randomization or first dose of drug
- Any of the following cardiovascular risk factors:
- Conditions occurring ≤ 28 days before first dose of study drug treatment: Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, symptomatic pulmonary embolism, any episode of syncope or seizure.
- Conditions occurring ≤ 6 months before first dose of study drug treatment: any history of acute myocardial infarction, any history of heart failure meeting New York Heart Association (NYHA) Classification III or IV, any event of ventricular arrhythmia ≥ Grade 2 in severity, any history of cerebrovascular accident
- Concurrent participation in another therapeutic clinical study.
- Was administered a live vaccine ≤ 4 weeks before first dose of study drug treatment.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
National Taiwan University Hospital
Taipei, Zhongzheng Dist, 100
Chiun Hsu, MD, PhD, +886-2-2312-3456 ext. 67482, chsu1967@ntu.edu.tw,hsuchiun@gmail.com
Chun Liu, BS, +886-2-2312-3456 ext. 67853, 105596@ntuh.gov.tw
About this study
Official title: Regorafenib Plus Tislelizumab as First-line Systemic Therapy for Patients With Advanced Hepatocellular Carcinoma (HCC)
Combination of anti-angiogenic molecular targeted therapy and anti- programmed cell death -1 immune checkpoint inhibitor (ICI) therapy has shown promising antitumor activity in multiple cancer types, including patients with advanced hepatocellular carcinoma (HCC). The safety profile and optimal dosage of targeted therapy should be carefully evaluated by clinical trials. Regorafenib is one of the standard second-line systemic therapy for advanced HCC. The present study will test the safety and efficacy of combination of regorafenib and tislelizumab, an anti-programmed cell death-1 ICI. The investigator(s) thus hypothesized that combination of tislelizumab and regorafenib is a tolerable regimen and may improve treatment efficacy for patients with advanced HCC. The present study will explore safety and efficacy of the combination of tislelizumab plus regorafenib as first-line therapy for advanced HCC.
Read the detailed description
Combination of ICI with anti-angiogenic therapy has been most extensively studies in patients with renal cell carcinoma, for whom both ICI and anti-angiogenic therapy have proven anticancer activity as single-agent therapy. Objective response rate of 30-60% was observed, far exceeding the response rate of single-agent therapy (around 20%). Results from several early-phase trials of this type of combination also support the potential anti-tumor synergy between ICI and anti-angiogenic therapy (multi-kinase inhibitors or monoclonal antibody targeting the vascular endothelial growth factor signaling pathway) in advanced HCC. Further studies should focus on identifying the optimal targeted agent and its biologically effective dosage to achieve the best therapeutic window for the treatment of HCC.
Current evidence indicated the following:
- Combination of ICI and anti-angiogenic therapy in advanced HCC may have better anti-tumor efficacy compared with single-agent therapy;
- The immune modulatory effects of the multi-kinase inhibitors may be achieved at dosage lower than recommended for single-agent therapy in the clinic; using this lower dosage when combined with ICI may lower the treatment-related adverse events.
- Objective response of 40% to 50% was recently reported in a phase 1 study of regorafenib plus nivolumab for patients with advanced gastric or colorectal cancer was reported recently (Fukuoka S, et al. American Society Of Clinical Oncology 2019, abstract#2522). Grade 3 or greater treatment-related adverse events were found in 27% of subjects who received regorafenib 80 mg per day and in 44% of patients who received regorafenib 120 mg per day. Therefore, regorafenib 80 mg/day was defined as the optimal dosage in combination with nivolumab.
- Conditions
- Advanced Hepatocellular Carcinoma
- Being tested
- Tislelizumab+regorafenib for part 1;Tislelizumab+regorafenib for group 1 of part 2; Regorafenib for group 2 of part 2.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tislelizumab+regorafenib for part 1;Tislelizumab+regorafenib for group 1 of part 2; Regorafenib for group 2 of part 2.Drug
Also called Stivarga, BAY-73-4506, BGB-A317
There will be no dose reduction for tislelizumab in this study. In the part 1(safety cohort), if the subjects do not experience grade 2 or greater regorafenib-related adverse events after 2 cycles (6 weeks) of treatment, the dosage of regorafenib may be escalated. For subjects who escalate the regorafenib dosage to Level 2, if the subjects do not experience grade 2 or greater regorafenib-related adverse events after 2 cycles of study drug treatment, the dosage of regorafenib may be further escalated to Level 3.
During study drug treatment, dose delay/ interruption of regorafenib will be done depending on the occurrence and severity of regorafenib-related adverse events. After dose reduction of regorafenib, if the subjects tolerate the reduced dose of regorafenib well, the investigators may consider re-escalation of regorafenib to the previous dose level, depending on the types and severity of adverse events that led to dose reduction.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Tislelizumab intravenously + regorafenib orally | Experimental | Part 1 is a single-arm study. All eligible patients will receive tislelizumab 200 mg intravenously on day 1 every 3 weeks plus regorafenib orally 80 mg per day. Receives: Drug: Tislelizumab+regorafenib for part 1;Tislelizumab+regorafenib for group 1 of part 2; Regorafenib for group 2 of part 2. |
| Groups (1) of part 2: Tislelizumab intravenously + regorafenib | Experimental | Tislelizumab 200 mg intravenously on Day 1+Regorafenib its dosage in the randomized cohort will be determined according to results in the safety cohort. Receives: Drug: Tislelizumab+regorafenib for part 1;Tislelizumab+regorafenib for group 1 of part 2; Regorafenib for group 2 of part 2. |
| Groups (2) of part 2: regorafenib | Active comparator | Daily dose of regorafenib 80mg/day is for week 1; Daily dose of regorafenib 120mg/day is for week 2; Daily dose of regorafenib 160mg/day is for week 3; Dosing-free interval is for week 4.
* The dose of regorafenib will not be escalated if treatment-related AE > grade 1 occurs at the previous dose level.
* For subjects in the group 2, when imaging evaluation of tumor response indicates stable disease or progressive disease, according to RECIST v1.1, study treatment will be shifted to regorafenib + tislelizumab combination regimen. Receives: Drug: Tislelizumab+regorafenib for part 1;Tislelizumab+regorafenib for group 1 of part 2; Regorafenib for group 2 of part 2. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety cohort: 14 participants with treatment related serious adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) V5.0.
14 or fewer participants who experience grade 3 or greater treatment-related adverse events at the 80 mg per day level, as defined by Common Terminology Criteria for Adverse Events (CTCAE)V5.0.
Measured: Day 1, Change from Day 1 to 23-37 days after the last dose of study drug treatment.
Randomized cohorts: Objective response rate (ORR) (co-primary)
The percentage of 100 participants with radiologically complete or partial response as determined by the investigator according to Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Measured: about 1 year
Randomized cohorts: Progression-free survival (PFS) (co-primary)
PFS is measured from the date of study enrollment to radiographically documented progression according to RECIST 1.1 or death from any cause (whichever occurs first).
Measured: about 1 year
Secondary outcomes (7)
Safety cohort: safety as assessed by 25 participants experiencing who incidence and severity of total AE, liver related AE, and immune-related AE.
25 participants experiencing who incidence and severity of total AE, liver related AE, and immune-related AE.as defined by Common Terminology Criteria for Adverse Events (CTCAE)V5.0.
Measured: Day 1, Change from Day 1 to 23-37 days after the last dose of study drug treatment.
Safety cohort: Proportion of 25 participants who may escalate the dose of regorafenib (continuous dosing) during study drug treatment
An adequate supply of regorafenib will be dispensed to participants on Day 1 of each new cycle (once every 3 weeks). Each time study drug is dispensed, compliance will be evaluated and encouraged. Treatment compliance will also be monitored by drug accountability log.
Measured: Day 1 of each cycle
Safety cohort: Objective response rate (ORR)
The percentage of 25 participants with radiologically complete or partial response as determined by the investigator according to both RECIST 1.1 and the immune-RECIST.
Measured: about 1 year
Randomized cohort: safety as assessed by 100 participants experiencing who incidence and severity of total AE, liver related AE, and immune-related AE.
100 participants experiencing who incidence and severity of total AE, liver related AE, and immune-related AE.as defined by Common Terminology Criteria for Adverse Events (CTCAE)V5.0.
Measured: Day 1, Change from Day 1 to 23-37 days after the last dose of study drug treatment.
Randomized cohort: Objective response rate (ORR)
The percentage of 100 participants with radiologically complete or partial response as determined by the investigator according to both RECIST 1.1 and the immune-RECIST.
Measured: about 1 year
Safety cohort: progression-free survival (PFS)
PFS is measured from the date of study enrollment to radiographically documented progression according to RECIST 1.1 and the immune-RECIST or death from any cause (whichever occurs first).
Measured: about 1 year
Randomized cohort: progression-free survival (PFS)
PFS is measured from the date of study enrollment to radiographically documented progression according to RECIST 1.1 and the immune-RECIST or death from any cause (whichever occurs first).
Measured: about 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2019
- Study start16 Dec 2020
- Primary completion1 Mar 2024 (estimated)
- Study completion1 Mar 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- This trial consists of 2 parts. Part 1 is a single-arm study. Part 2 of this trial is a randomized study. Subjects will be 1:1 randomized to 2 treatment groups: (1) regorafenib + tislelizumab combination regimen as used in Part 1, versus (2) regorafenib therapy. For subjects in the group 2, when imaging evaluation of tumor response indicates stable disease or progressive disease, according to RECIST v1.1, study treatment will be shifted to regorafenib + tislelizumab combination regimen.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 125 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Taiwan University Hospital, Yun-Lin Branch
- Responsible party
- Sponsor
- Investigators
- Ann-Lii Cheng, MD, PhD, Principal investigator, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04183088
- Sponsor's protocol ID
- 201911021MIFB
- Status last verified
- Dec 2020
- First submitted
- 25 Nov 2019
- Last updated
- 23 Dec 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regorafenib Plus Tislelizumab as First-line Systemic Therapy for Patients With Advanced Hepatocellular Carcinoma (HCC)
- ClinicalTrials.gov ID
- NCT04183088
- Acronym / sponsor ID
- 201911021MIFB
- Conditions
- Advanced Hepatocellular Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 125 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Collaborators
- National Taiwan University Hospital, Yun-Lin Branch
- Study start
- 16 Dec 2020 (actual)
- Primary completion
- 1 Mar 2024 (estimated)
- Study completion
- 1 Mar 2025 (estimated)
- First posted
- 3 Dec 2019 (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.
Combination of anti-angiogenic molecular targeted therapy and anti- programmed cell death -1 immune checkpoint inhibitor (ICI) therapy has shown promising antitumor activity in multiple cancer types, including patients with advanced hepatocellular carcinoma (HCC). The safety profile and optimal dosage of targeted therapy should be carefully evaluated by clinical trials. Regorafenib is one of the standard second-line systemic therapy for advanced HCC. The present study will test the safety and efficacy of combination of regorafenib and tislelizumab, an anti-programmed cell death-1 ICI. The investigator(s) thus hypothesized that combination of tislelizumab and regorafenib is a tolerable regimen and may improve treatment efficacy for patients with advanced HCC. The present study will explore safety and efficacy of the combination of tislelizumab plus regorafenib as first-line therapy for advanced HCC.
Detailed description
Combination of ICI with anti-angiogenic therapy has been most extensively studies in patients with renal cell carcinoma, for whom both ICI and anti-angiogenic therapy have proven anticancer activity as single-agent therapy. Objective response rate of 30-60% was observed, far exceeding the response rate of single-agent therapy (around 20%). Results from several early-phase trials of this type of combination also support the potential anti-tumor synergy between ICI and anti-angiogenic therapy (multi-kinase inhibitors or monoclonal antibody targeting the vascular endothelial growth factor signaling pathway) in advanced HCC. Further studies should focus on identifying the optimal targeted agent and its biologically effective dosage to achieve the best therapeutic window for the treatment of HCC.
Current evidence indicated the following:
- Combination of ICI and anti-angiogenic therapy in advanced HCC may have better anti-tumor efficacy compared with single-agent therapy;
- The immune modulatory effects of the multi-kinase inhibitors may be achieved at dosage lower than recommended for single-agent therapy in the clinic; using this lower dosage when combined with ICI may lower the treatment-related adverse events.
- Objective response of 40% to 50% was recently reported in a phase 1 study of regorafenib plus nivolumab for patients with advanced gastric or colorectal cancer was reported recently (Fukuoka S, et al. American Society Of Clinical Oncology 2019, abstract#2522). Grade 3 or greater treatment-related adverse events were found in 27% of subjects who received regorafenib 80 mg per day and in 44% of patients who received regorafenib 120 mg per day. Therefore, regorafenib 80 mg/day was defined as the optimal dosage in combination with nivolumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
- Model description
- This trial consists of 2 parts. Part 1 is a single-arm study. Part 2 of this trial is a randomized study. Subjects will be 1:1 randomized to 2 treatment groups: (1) regorafenib + tislelizumab combination regimen as used in Part 1, versus (2) regorafenib therapy. For subjects in the group 2, when imaging evaluation of tumor response indicates stable disease or progressive disease, according to RECIST v1.1, study treatment will be shifted to regorafenib + tislelizumab combination regimen.
| Arm | Type | Receives |
|---|---|---|
| Part 1: Tislelizumab intravenously + regorafenib orally | Experimental | Drug: Tislelizumab+regorafenib for part 1;Tislelizumab+regorafenib for group 1 of part 2; Regorafenib for group 2 of part 2.Part 1 is a single-arm study. All eligible patients will receive tislelizumab 200 mg intravenously on day 1 every 3 weeks plus regorafenib orally 80 mg per day. |
| Groups (1) of part 2: Tislelizumab intravenously + regorafenib | Experimental | Drug: Tislelizumab+regorafenib for part 1;Tislelizumab+regorafenib for group 1 of part 2; Regorafenib for group 2 of part 2.Tislelizumab 200 mg intravenously on Day 1+Regorafenib its dosage in the randomized cohort will be determined according to results in the safety cohort. |
| Groups (2) of part 2: regorafenib | Active comparator | Drug: Tislelizumab+regorafenib for part 1;Tislelizumab+regorafenib for group 1 of part 2; Regorafenib for group 2 of part 2.Daily dose of regorafenib 80mg/day is for week 1; Daily dose of regorafenib 120mg/day is for week 2; Daily dose of regorafenib 160mg/day is for week 3; Dosing-free interval is for week 4. * The dose of regorafenib will not be escalated if treatment-related AE > grade 1 occurs at the previous dose level. * For subjects in the group 2, when imaging evaluation of tumor response indicates stable disease or progressive disease, according to RECIST v1.1, study treatment will be shifted to regorafenib + tislelizumab combination regimen. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments
- Age ≥ 20 years, according to local regulation in Taiwan, at time of signing Informed Consent Form.
- Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology.
- Disease that is not amenable to curative surgical and/or locoregional therapies, or progressive disease after surgical and /or locoregional therapies
- Agreement to have a new tumor biopsy for eligibility to this study
Key exclusion criteria (32 listed)
- Histological diagnosis of fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
- Liver tumor(s) with main portal vein thrombosis.
- Known human immunodeficiency virus (HIV) infection.
- History of esophageal/gastric varices or active peptic ulcers that are considered to have high risk of bleeding.
- History of upper gastrointestinal bleeding within 1 year.
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 |
|---|---|---|
| Tislelizumab+regorafenib for part 1;Tislelizumab+regorafenib for group 1 of part 2; Regorafenib for group 2 of part 2.Also: Stivarga, BAY-73-4506, BGB-A317There will be no dose reduction for tislelizumab in this study. In the part 1(safety cohort), if the subjects do not experience grade 2 or greater regorafenib-related adverse events after 2 cycles (6 weeks) of treatment, the dosage of regorafenib may be escalated. For subjects who escalate the regorafenib dosage to Level 2, if the subjects do not experience grade 2 or greater regorafenib-related adverse events after 2 cycles of study drug treatment, the dosage of regorafenib may be further escalated to Level 3. During study drug treatment, dose delay/ interruption of regorafenib will be done depending on the occurrence and severity of regorafenib-related adverse events. After dose reduction of regorafenib, if the subjects tolerate the reduced dose of regorafenib well, the investigators may consider re-escalation of regorafenib to the previous dose level, depending on the types and severity of adverse events that led to dose reduction. | Drug | Groups (1) of part 2: Tislelizumab intravenously + regorafenib, Groups (2) of part 2: regorafenib, Part 1: Tislelizumab intravenously + regorafenib orally |
Primary outcome
Safety cohort: 14 participants with treatment related serious adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) V5.0.
Time frame: Day 1, Change from Day 1 to 23-37 days after the last dose of study drug treatment.
14 or fewer participants who experience grade 3 or greater treatment-related adverse events at the 80 mg per day level, as defined by Common Terminology Criteria for Adverse Events (CTCAE)V5.0.
Randomized cohorts: Objective response rate (ORR) (co-primary)
Time frame: about 1 year
The percentage of 100 participants with radiologically complete or partial response as determined by the investigator according to Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Randomized cohorts: Progression-free survival (PFS) (co-primary)
Time frame: about 1 year
PFS is measured from the date of study enrollment to radiographically documented progression according to RECIST 1.1 or death from any cause (whichever occurs first).
7 secondary outcomes
Safety cohort: safety as assessed by 25 participants experiencing who incidence and severity of total AE, liver related AE, and immune-related AE.
Time frame: Day 1, Change from Day 1 to 23-37 days after the last dose of study drug treatment.
Safety cohort: Proportion of 25 participants who may escalate the dose of regorafenib (continuous dosing) during study drug treatment
Time frame: Day 1 of each cycle
Safety cohort: Objective response rate (ORR)
Time frame: about 1 year
Randomized cohort: safety as assessed by 100 participants experiencing who incidence and severity of total AE, liver related AE, and immune-related AE.
Time frame: Day 1, Change from Day 1 to 23-37 days after the last dose of study drug treatment.
Randomized cohort: Objective response rate (ORR)
Time frame: about 1 year
Safety cohort: progression-free survival (PFS)
Time frame: about 1 year
Randomized cohort: progression-free survival (PFS)
Time frame: about 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2020.
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Hepatocellular Cancer, Liver Cancer
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.
Ann-Lii Cheng, MD, PhD principal investigator
National Taiwan University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tislelizumab+regorafenib for part 1;Tislelizumab+regorafenib for group 1 of part 2; Regorafenib for group 2 of part 2. in people with Advanced Hepatocellular Carcinoma, run by National Taiwan University Hospital at 1 site in Taiwan.
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 18 inclusion and 32 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 23 Dec 2020. 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 Taiwan. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Contact Chiun HSU, MD, PhD (+886-2312-3456 ext. 67482, chsu1967@ntu.edu.tw,hsuchiun@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety cohort: 14 participants with treatment related serious adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) V5.0. (time frame: Day 1, Change from Day 1 to 23-37 days after the last dose of study drug treatment.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Dec 2020.