Hepatocellular CarcinomaPhase 2NCT05809869
Immunotherapy and Radioembolisation for Metastatic Hepatocellular Carcinoma
A Phase 2 study testing Durvalumab, Tremelimumab and Yttrium-90 radioembolisation in people with Hepatocellular Carcinoma, run by The University of Hong Kong at 1 site in Hong Kong.
Trial summary
Hepatocellular carcinoma is one of the most intractable primary malignancies in the hepatobiliary and pancreatic tract with a poor overall survival worldwide. Unfortunately, the vast majority of hepatocellular carcinoma patients suffer from advanced unresectable or metastatic disease at diagnosis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Durvalumab, Tremelimumab and Yttrium-90 radioembolisation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteHong Kong
- Study dates
- 15 Feb 2023to 30 Jun 2026
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Metastatic hepatocellular carcinoma (HCC) confirmed by radiological findings with contrast-enhanced triphasic CT scan of the liver and/or MRI scan of the abdomen, without or without histological/cytological confirmation or elevation of serum alpha-feto protein.
- Must be of age 18 years or above.
- Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry.
- Must be eligible to receive immune checkpoint inhibitor and yttrium-90 microsphere injection.
- Must have baseline efficacy images with CT or MRI and measurable target lesions in the liver according to RECIST 1.1 and mRECIST, taken within 28 days prior to the start of immune checkpoint inhibitor.
- Must be able to provide written informed consent.
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- Adequate serum hematological functions defined as:
- Absolute neutrophil count (ANC) ≥1.0 x 10^9/l Platelet ≥75 x 10^9/l Haemoglobin ≥9 g/dL
- Adequate serum biochemistry functions defined as:
- Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). <<This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.>> Serum aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤2.5 times of institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5 times of ULN
- Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
- Males:
- Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)
- Females:
- Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)
Who cannot join
- Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment or 5 half-lives, whichever is shorter.
- Has a diagnosis of severe active scleroderma, lupus, other rheumatologic or autoimmune disease within the past 3 months before study recruitment. Patients with a documented history of clinically severe autoimmune disease or a syndrome requiring systemic steroids or immunosuppressive agents will not be allowed on this study. Subjects with vitiligo or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections are not excluded from the study. Subjects with hypothyroidism stable on hormone replacement are not excluded from this study.
- Has had a prior monoclonal antibody, immunotherapy or immune checkpoint inhibitors before recruitment into this study.
- Has had prior chemotherapy or targeted small molecule therapy (including sorafenib or other anti-vascular endothelial growth factor inhibitor) within 3 weeks prior to administration of the study drug or who has not recovered (i.e., grade ≤1 or at baseline) from adverse events due to a previously administered agent.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, indolent lymphomas, or in situ cervical cancer that has undergone potentially curative therapy.
- Has known carcinomatous meningitis (also known as leptomeningeal carcinomatosis).
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- Has an active infection requiring intravenous systemic therapy or hospital admission.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality, including psychiatric or substance abuse disorder, that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 31 weeks after the last dose of trial treatment.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). Routine checking for Anti-HIV1 or Anti-HIV2 is not mandatory.
- Untreated hepatitis B infection. Patients with chronic hepatitis B infection (defined as HBsAg positive) are eligible if they have started anti-viral therapy for at least 1 month and is continuing anti-viral treatment throughout the whole duration of this study.
- Has experienced Grade 4 toxicity on treatment with prior radiation.
- Has experienced grade 3-4 intracranial toxicity (hypophysitis or central nervous system toxicity) with either prior intracranial radiation, anti-programmed cell death-1 (PD-1), or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor therapy.
- Is taking >4mg/day of dexamethasone or its equivalent at the start of immunotherapy or has required >4mg/day of dexamethasone or its equivalent for 3 consecutive days within 1 week of starting treatment.
- Allergies and adverse drug reaction to the following: History of allergy to study drug components; History of severe hypersensitivity reaction to any monoclonal antibody.
- Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study medication. Note: Local surgery of isolated lesions for palliative intent is acceptable.
- Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart).
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) (B) Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of prednisone or its equivalent (C) Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
Trial locations and contacts
1 site in 1 country.
Hong Kong1 site, 1 recruiting
- Recruiting
Department of Clinical Oncology, Queen Mary Hospital
Hong Kong
Victor Ho-Fun Lee, MD, 852-2255-4352, vhflee@hku.hk
Mike Law, BSc, 852-2255-5034, lawhc703@hku.hk
About this study
Official title: A Phase 2 Study on Immune Checkpoint Inhibitors and Radioembolisation for Previously Untreated Metastatic Hepatocellular Carcinoma
Hepatocellular carcinoma is one of the most intractable primary malignancies in the hepatobiliary and pancreatic tract with a poor overall survival worldwide. Unfortunately, the vast majority of hepatocellular carcinoma patients suffer from advanced unresectable or metastatic disease at diagnosis. Currently targeted therapy alone, or in combination with anti-vascular endothelial growth factor antagonist, is the standard first-line treatment for metastatic hepatocellular carcinoma.
On the other hand, there is growing evidence suggesting that radiation therapy (external or internal) with or without immune checkpoint inhibitors can produce or even augment abscopal effect in which the tumours away from the radiation field also show significant tumour shrinkage. The underlying mechanism of eliciting abscopal effect includes the increased antigen presentation by the myeloid cells within the tumour stroma leading to enhanced tumour cell killing. Previous case reports showed that radiation therapy alone can induce abscopal effect in mice and human models. However, a robust and concrete evidence of abscopal effect with combinational immune checkpoint inhibitors and radioembolisation or external radiation therapy in hepatocellular carcinoma is still lacking.
This study investigates the efficacy and safety of immune checkpoint inhibitors and radioembolisation as first-line treatment for previously untreated metastatic hepatocellular carcinoma.
Read the detailed description
Hepatocellular carcinoma is one of the most intractable primary malignancies in the hepatobiliary and pancreatic tract with a poor overall survival worldwide. Surgery in the form of hepatectomy or liver transplantation provides the best chance of cure for early-stage disease. Unfortunately, the vast majority of hepatocellular carcinoma patients suffer from advanced unresectable or metastatic disease at diagnosis. Currently targeted therapy alone, or in combination with anti-vascular endothelial growth factor antagonist, is the standard first-line treatment for metastatic hepatocellular carcinoma.
On the other hand, there is growing evidence suggesting that radiation therapy (external or internal) with or without immune checkpoint inhibitors can produce or even augment abscopal effect in which the tumours away from the radiation field also show significant tumour shrinkage. The underlying mechanism of eliciting abscopal effect includes the increased antigen presentation by the myeloid cells within the tumour stroma leading to enhanced tumour cell killing. Previous case reports showed that radiation therapy alone can induce abscopal effect in mice and human models. However, a robust and concrete evidence of abscopal effect with combinational immune checkpoint inhibitors and radioembolisation or external radiation therapy in hepatocellular carcinoma is still lacking.
This phase 2 single-arm study will investigate the efficacy and safety of combination of immune checkpoint inhibitors and radioembolisation for previously untreated metastatic hepatocellular carcinoma.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Durvalumab, Tremelimumab, Yttrium-90 radioembolisation
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Also called MEDI4736
Durvalumab 1500mg intravenous infusion on week 1, 5, 9, 13, 17, 21 and 25 for a total of 7 cycles
TremelimumabDrug
Also called Imjudo
Tremelimumab 300mg intravenous infusion on week 1 only.
Yttrium-90 radioembolisationRadiation
Yttrium-90 radioembolisation on week 2 only.
| Study group | Role | What they receive |
|---|---|---|
| Durvalumab in combination with tremelimumab and radioembolisation | Experimental | 1. Tremelimumab 300 mg intravenous infusion on week 1 only
2. Durvalumab 1500mg intravenous infusion on week 1, 5, 9, 13, 17, 21 and 25, for a total of 7 cycles
3. Radioembolisation with yttrium-90 microspheres on week 2 only Receives: Drug: Durvalumab; Drug: Tremelimumab; Radiation: Yttrium-90 radioembolisation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best objective response
Best objective response
Measured: 3 years
Rate of abscopal effect
Rate of abscopal effect, which is defined as the rate of objective response of tumour sites outside the liver after radioembolisation and immune checkpoint inhibitor therapy
Measured: 3 years
Secondary outcomes (5)
Progression-free survival
Progression-free survival
Measured: 3 years
Overall survival
Overall survival
Measured: 3 years
Incidence of treatment-related side effects
Incidence of treatment-related side effects as determined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Measured: 3 years
Local control rate
Local control rate, which is defined as the percentage of tumour sites in the liver without evidence of progressive disease after radioembolisation and immune checkpoint inhibitor therapy
Measured: 3 years
Distant control rate
Distant control rate, which is defined as the percentage of tumour sites outside the liver without evidence of progressive disease after radioembolisation and immune checkpoint inhibitor therapy
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2023
- Study start15 Feb 2023
- Primary completion31 Dec 2025 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe 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
- Not applicable
- Intervention model
- Single group
- Model description
- Immune checkpoint inhibitors and radioembolisation for previously untreated metastatic hepatocellular carcinoma
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Collaborators
- Queen Mary Hospital, Hong Kong
- Responsible party
- Sponsor
- Investigators
- Victor Ho-Fun Lee, MD, Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05809869
- Sponsor's protocol ID
- UW 22-729
- Status last verified
- Feb 2023
- First submitted
- 26 Feb 2023
- Last updated
- 12 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to make individual participant data (IPD) available to other researchers.
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study on Immune Checkpoint Inhibitors and Radioembolisation for Previously Untreated Metastatic Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT05809869
- Acronym / sponsor ID
- UW 22-729
- Conditions
- Hepatocellular Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Collaborators
- Queen Mary Hospital, Hong Kong
- Study start
- 15 Feb 2023 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 12 Apr 2023 (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.
Hepatocellular carcinoma is one of the most intractable primary malignancies in the hepatobiliary and pancreatic tract with a poor overall survival worldwide. Unfortunately, the vast majority of hepatocellular carcinoma patients suffer from advanced unresectable or metastatic disease at diagnosis. Currently targeted therapy alone, or in combination with anti-vascular endothelial growth factor antagonist, is the standard first-line treatment for metastatic hepatocellular carcinoma.
On the other hand, there is growing evidence suggesting that radiation therapy (external or internal) with or without immune checkpoint inhibitors can produce or even augment abscopal effect in which the tumours away from the radiation field also show significant tumour shrinkage. The underlying mechanism of eliciting abscopal effect includes the increased antigen presentation by the myeloid cells within the tumour stroma leading to enhanced tumour cell killing. Previous case reports showed that radiation therapy alone can induce abscopal effect in mice and human models. However, a robust and concrete evidence of abscopal effect with combinational immune checkpoint inhibitors and radioembolisation or external radiation therapy in hepatocellular carcinoma is still lacking.
This study investigates the efficacy and safety of immune checkpoint inhibitors and radioembolisation as first-line treatment for previously untreated metastatic hepatocellular carcinoma.
Detailed description
Hepatocellular carcinoma is one of the most intractable primary malignancies in the hepatobiliary and pancreatic tract with a poor overall survival worldwide. Surgery in the form of hepatectomy or liver transplantation provides the best chance of cure for early-stage disease. Unfortunately, the vast majority of hepatocellular carcinoma patients suffer from advanced unresectable or metastatic disease at diagnosis. Currently targeted therapy alone, or in combination with anti-vascular endothelial growth factor antagonist, is the standard first-line treatment for metastatic hepatocellular carcinoma.
On the other hand, there is growing evidence suggesting that radiation therapy (external or internal) with or without immune checkpoint inhibitors can produce or even augment abscopal effect in which the tumours away from the radiation field also show significant tumour shrinkage. The underlying mechanism of eliciting abscopal effect includes the increased antigen presentation by the myeloid cells within the tumour stroma leading to enhanced tumour cell killing. Previous case reports showed that radiation therapy alone can induce abscopal effect in mice and human models. However, a robust and concrete evidence of abscopal effect with combinational immune checkpoint inhibitors and radioembolisation or external radiation therapy in hepatocellular carcinoma is still lacking.
This phase 2 single-arm study will investigate the efficacy and safety of combination of immune checkpoint inhibitors and radioembolisation for previously untreated metastatic hepatocellular carcinoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Immune checkpoint inhibitors and radioembolisation for previously untreated metastatic hepatocellular carcinoma
| Arm | Type | Receives |
|---|---|---|
| Durvalumab in combination with tremelimumab and radioembolisation | Experimental | Drug: Durvalumab, Drug: Tremelimumab, Radiation: Yttrium-90 radioembolisation1. Tremelimumab 300 mg intravenous infusion on week 1 only 2. Durvalumab 1500mg intravenous infusion on week 1, 5, 9, 13, 17, 21 and 25, for a total of 7 cycles 3. Radioembolisation with yttrium-90 microspheres on week 2 only |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Metastatic hepatocellular carcinoma (HCC) confirmed by radiological findings with contrast-enhanced triphasic CT scan of the liver and/or MRI scan of the abdomen, without or without histological/cytological confirmation or elevation of serum alpha-feto protein.
- Must be of age 18 years or above.
- Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry.
- Must be eligible to receive immune checkpoint inhibitor and yttrium-90 microsphere injection.
- Must have baseline efficacy images with CT or MRI and measurable target lesions in the liver according to RECIST 1.1 and mRECIST, taken within 28 days prior to the start of immune checkpoint inhibitor.
Key exclusion criteria (19 listed)
- Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment or 5 half-lives, whichever is shorter.
- Has a diagnosis of severe active scleroderma, lupus, other rheumatologic or autoimmune disease within the past 3 months before study recruitment. Patients with a documented history of clinically severe autoimmune disease or a syndrome requiring systemic steroids or immunosuppressive agents will not be allowed on this study. Subjects with vitiligo or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections are not excluded from the study. Subjects with hypothyroidism stable on hormone replacement are not excluded from this study.
- Has had a prior monoclonal antibody, immunotherapy or immune checkpoint inhibitors before recruitment into this study.
- Has had prior chemotherapy or targeted small molecule therapy (including sorafenib or other anti-vascular endothelial growth factor inhibitor) within 3 weeks prior to administration of the study drug or who has not recovered (i.e., grade ≤1 or at baseline) from adverse events due to a previously administered agent.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, indolent lymphomas, or in situ cervical cancer that has undergone potentially curative therapy.
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 |
|---|---|---|
| DurvalumabAlso: MEDI4736Durvalumab 1500mg intravenous infusion on week 1, 5, 9, 13, 17, 21 and 25 for a total of 7 cycles | Drug | Durvalumab in combination with tremelimumab and radioembolisation |
| TremelimumabAlso: ImjudoTremelimumab 300mg intravenous infusion on week 1 only. | Drug | Durvalumab in combination with tremelimumab and radioembolisation |
| Yttrium-90 radioembolisationYttrium-90 radioembolisation on week 2 only. | Radiation | Durvalumab in combination with tremelimumab and radioembolisation |
Primary outcome
Best objective response
Time frame: 3 years
Best objective response
Rate of abscopal effect
Time frame: 3 years
Rate of abscopal effect, which is defined as the rate of objective response of tumour sites outside the liver after radioembolisation and immune checkpoint inhibitor therapy
5 secondary outcomes
Progression-free survival
Time frame: 3 years
Overall survival
Time frame: 3 years
Incidence of treatment-related side effects
Time frame: 3 years
Local control rate
Time frame: 3 years
Distant control rate
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2023.
- Individual participant dataSharing planned: No. There is no plan to make individual participant data (IPD) available to other researchers.
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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.
Victor Ho-Fun Lee, MD principal investigator
The University of Hong Kong
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 Durvalumab, Tremelimumab and Yttrium-90 radioembolisation in people with Hepatocellular Carcinoma, run by The University of Hong Kong at 1 site in Hong Kong.
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 15 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 12 Apr 2023. 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 Hong Kong. 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 Victor Ho-Fun Lee, MD (852-2255-4352, vhflee@hku.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best objective response (time frame: 3 years). The study lists 2 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 12 Apr 2023.