Hepatocellular Carcinoma (HCC)Phase 2NCT06605664
Hyperpolarized 13C-MRI in Patients With Hepatocellular Carcinoma Undergoing Radiotherapy, Atezolizumab, and Bevacizumab
A Phase 2 study testing Hyperpolarized 13C pyruvate MRI in people with Hepatocellular Carcinoma (HCC), run by Chang Gung Memorial Hospital at 1 site in Taiwan.
Trial summary
Increased pyruvate-to-lactate conversion is a hallmark of HCC metabolism. In parallel, activation of pro-inflammatory immune cells triggers a metabolic switch towards anaerobic glycolysis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma (HCC)
- What is being tested?
- Hyperpolarized 13C pyruvate MRI
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 May 2025to 30 Sep 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Participants must have diagnosis of HCC that is deemed unsuitable for surgical resection or transplant and will undergo radiotherapy, atezolizumab, and bevacizumab. Participants may have multiple lesions with a total maximal tumor dimension of \< 20 cm, and no one lesion \> 15 cm. Diagnosis should be confirmed by at least 1 criteria listed below:
- Histologically or cytologically proven diagnosis of HCC.
- Typical arterial enhancement and delayed washout on multiphasic CT or MRI.
- Age ≥18 years at the time of signing informed consent document.
- ECOG performance status 0-1.
- Barcelona Clinic Liver Cancer (BCLC) stages Intermediate (B) or Advanced (C).
Show all 20Show fewer
- Child-Pugh score 5-6 liver function within 28 days of study registration.
- Documented virology status of hepatitis B virus (HBV), as confirmed by screening HBV serology test.
- Documented virology status of hepatitis C virus (HCV), as confirmed by screening HCV serology test.
- Ability to understand and the willingness to sign a written informed consent document
- Adequate bone marrow, liver, and renal function within 4 weeks before study registration
- Hemoglobin ≥ 9.0 g/dL
- Absolute neutrophil count (ANC) ≥ 1,000/mm3
- Platelet count ≥ 50,000/μL
- Total bilirubin \< 2.5 mg/dL
- Serum albumin \>2.8 g/dL
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN)
- Prothrombin time ≤ 6 seconds prolonged
- Serum creatinine ≤ 1.5 mg/dL
- The medical team, experienced in liver cancer treatment, has evaluated and confirmed that the benefits outweigh the risks for participants receiving proton or photon radiation therapy combined with atezolizumab and bevacizumab.
Who cannot join
- Prior invasive malignancy unless disease free for a minimum of 2 years
- Prior radiotherapy to the region of the liver that would result in overlap of radiation therapy fields
- Prior selective internal radiotherapy/hepatic arterial yttrium therapy, at any time
- Untreated active hepatitis B or hepatitis C
- Moderate to severe or intractable ascites
- Presence of distant metastases
Show all 25Show fewer
- Untreated or incomplete treated esophageal or gastric varices
- Severe, active co-morbidity, defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to registration
- Myocardial infarction within the last 6 months prior to study entry
- Acute bacterial or fungal infection requiring intravenous antibiotics within 28 days prior to study entry
- A bleeding episode within 6 months prior to study entry due to any cause.
- Thrombolytic therapy within 28 days prior to study entry.
- Known bleeding or clotting disorder.
- Uncontrolled psychotic disorder
- Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
- Prior solid organ transplantation.
- Prior or active autoimmune disease (AID) including autoimmune hepatitis, inflammatory bowel disease, myasthenia gravis, systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, and multiple sclerosis.
- Prior or active thrombotic or bleeding disorders, hemoptysis, cerebral vascular accident, significant cardiac disease (ischemic or congestive heart failure), or gastrointestinal perforation.
- Inability to treat all sites of disease by proton radiotherapy (such as extrahepatic metastases or massive liver tumors whereby the liver constraints cannot be met for covering all sites of liver tumors using radiotherapy.)
- Known HIV infection.
- Conditions not suitable for magnetic resonance imaging (MRI) include the presence of strongly magnetic arterial clips in the brain, cardiac pacemakers, cochlear implants, and claustrophobia.
- Concurrent medical conditions that may impact patients during MRI examination include active infections, symptomatic congestive heart failure, uncontrollable angina, arrhythmias, mental disorders, difficulty breathing, or diarrhea.
- An endoscopy report within the past six months indicates a high risk for upper gastrointestinal bleeding, and the patient has not received complete treatment for its prevention.
- Individuals who are allergic to hyperpolarized 13C pyruvate, atezolizumab, bevacizumab, or any ingredients contained in these medications.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Taiwan1 site, 1 recruiting
- Recruiting
Chang Gung Memorial Hospital at Linkou
Taoyuan City, Taiwan, 333
Rodney Cheng-En Hsieh, MD, PhD, +886-3-328-1200 ext. 7000, rodney445@gmail.com
Rodney Cheng En HSIEH, MD, PhD
About this study
Official title: Hyperpolarized 13C-MRI, Metabolomics, and Radiomics for Immune Response Prediction in Patients With Hepatocellular Carcinoma Undergoing Radiotherapy, Atezolizumab, and Bevacizumab
Increased pyruvate-to-lactate conversion is a hallmark of HCC metabolism. In parallel, activation of pro-inflammatory immune cells triggers a metabolic switch towards anaerobic glycolysis. Hyperpolarized carbon-13 (13C) pyruvate MRI is a state-of-the-art non-invasive imaging method that offers real-time insights into tissue metabolism. Recent studies have demonstrated its promising potential in predicting responses to radiotherapy and immunotherapy in solid tumors, given the significance of pyruvate as a downstream metabolite in glycolysis. However, its application in assessing treatment response in hepatocellular carcinoma (HCC) patients remains unclear. The establishment of quantitative imaging biomarkers for predicting responses to radio-immunotherapy is an unmet need in the management of HCC patients.
While radiotherapy (RT) effectively controls localized tumors through the induction of unrepairable DNA double-stranded breaks (DSBs) and cell death, its therapeutic efficacy on distal, non-irradiated tumor cells is limited, with out-of-field recurrence being a common pattern of failure in HCC patients treated with high-dose irradiation. Atezolizumab (anti-programmed death-ligand 1; anti-PD-L1) in conjunction with bevacizumab (anti-vascular endothelial growth factor; anti-VEGF) has recently emerged as the standard first-line systemic treatment for unresectable hepatocellular carcinoma (HCC). Despite an objective response rate (ORR) of only 27%, the majority of patients succumb to HCC progression and liver failure. Our preclinical study (Hsieh et al., Science Immunology 2022) uncovered that RT, when combined with PD-L1/PD-1 blockade, induces immunogenic cell death and tumor antigen cross-presentation in antigen-presenting cells, enhancing systemic antitumor T cell responses in murine tumor models. Recent retrospective cohorts suggest that RT targeting all hepatic tumors combined with PD-L1/programmed death-1 (PD-1) blockade is associated with an improved ORR and median progression-free survival (PFS) in patients with unresectable HCC, demonstrating a favorable safety profile. The synergistic antitumor effects of this combination therapy with RT, atezolizumab, and bevacizumab have led to its increasing adoption in routine clinical practice.
This phase II non-randomized trial aims to prospectively investigate the predictive value of hyperpolarized 13C-MRI, along with comprehensive metabolomics and radiomics analyses, for immune response assessment including tumor control outcomes and toxicity in patients with HCC undergoing radiotherapy, atezolizumab, and bevacizumab.
- Conditions
- Hepatocellular Carcinoma (HCC)
- Being tested
- Hyperpolarized 13C pyruvate MRI
- Keywords
- Hyperpolarized 13C-MRI, HCC, Radiotherapy, Metabolomics, Atezolizumab, Bevacizumab
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyperpolarized 13C pyruvate MRIDiagnostic test
The subject enrolled in this trial will receive DNP-MRI scanning for two times through hyperpolarized [1-13C]pyruvate injection (~250 mM, 0.43 mL/Kg) before and 2-5 weeks after radiotherapy.
| Study group | Role | What they receive |
|---|---|---|
| Hyperpolarized 13C pyruvate MRI | Experimental | Hyperpolarized 13C pyruvate MRI before and 2-5 weeks after radiotherapy combined with atezolizumab and bevacizumab Receives: Diagnostic Test: Hyperpolarized 13C pyruvate MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dynamic Nuclear Polarization (DNP)
Dynamic Nuclear Polarization (DNP) conversion flux (pyruvate-to-lactate conversion rate [Kpl] and area under the curve [AUC]) before radiotherapy combined with atezolizumab and bevacizumab
Measured: 4 months
Dynamic Nuclear Polarization (DNP)
Dynamic Nuclear Polarization (DNP) conversion flux (pyruvate-to-lactate conversion rate [Kpl] and area under the curve [AUC]) 2-5 weeks after radiotherapy combined with atezolizumab and bevacizumab
Measured: 4 month
Secondary outcomes (6)
Progression free survival (PFS) by RECIST1.1
PFS is defined as the time from signing the informed consent to the first occurrence of disease progression or death from any cause (whichever occurs first) according to RECIST1.1
Measured: 12 months
Local control (LC) by RECIST1.1
LC is defined as the time from signing the informed consent to the first occurrence of disease progression in the irradiated field according to RECIST1.1
Measured: 12 months
Time to progression (TTP) by RECIST1.1
TTP is defined as the time from signing the informed consent to the first occurrence of disease progression according to RECIST1.1
Measured: 12 months
Overall Response Rate (ORR) by RECIST1.1
ORR is defined as a complete or partial response according to RECIST1.1
Measured: 12 months
Overall survival (OS)
OS is defined as the time from signing the informed consent to death from any cause.
Measured: 12 months
Incidence and severity of adverse events
Adverse events will be graded using CTCAE v5
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2024
- Study start1 May 2025
- Primary completion30 Jun 2029 (estimated)
- Study completion30 Sep 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular Carcinoma (HCC)Studies of the same condition, open and under way.
- More trials run by Chang Gung Memorial 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
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm of hyperpolarized 13C pyruvate MRI
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chang Gung Memorial Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Cheng-En Hsieh, Chang Gung Memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06605664
- Sponsor's protocol ID
- 2401190005
- Status last verified
- Sep 2026
- First submitted
- 18 Sep 2024
- Last updated
- 29 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: The sharing of individual participant data (IPD) requires IRB approval.
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hyperpolarized 13C-MRI, Metabolomics, and Radiomics for Immune Response Prediction in Patients With Hepatocellular Carcinoma Undergoing Radiotherapy, Atezolizumab, and Bevacizumab
- ClinicalTrials.gov ID
- NCT06605664
- Acronym / sponsor ID
- 2401190005
- Conditions
- Hepatocellular Carcinoma (HCC)
- Keywords
- Hyperpolarized 13C-MRI, HCC, Radiotherapy, Metabolomics, Atezolizumab, Bevacizumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Chang Gung Memorial HospitalUniversity, hospital or other
- Study start
- 1 May 2025 (actual)
- Primary completion
- 30 Jun 2029 (estimated)
- Study completion
- 30 Sep 2031 (estimated)
- First posted
- 20 Sep 2024 (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.
Increased pyruvate-to-lactate conversion is a hallmark of HCC metabolism. In parallel, activation of pro-inflammatory immune cells triggers a metabolic switch towards anaerobic glycolysis. Hyperpolarized carbon-13 (13C) pyruvate MRI is a state-of-the-art non-invasive imaging method that offers real-time insights into tissue metabolism. Recent studies have demonstrated its promising potential in predicting responses to radiotherapy and immunotherapy in solid tumors, given the significance of pyruvate as a downstream metabolite in glycolysis. However, its application in assessing treatment response in hepatocellular carcinoma (HCC) patients remains unclear. The establishment of quantitative imaging biomarkers for predicting responses to radio-immunotherapy is an unmet need in the management of HCC patients.
While radiotherapy (RT) effectively controls localized tumors through the induction of unrepairable DNA double-stranded breaks (DSBs) and cell death, its therapeutic efficacy on distal, non-irradiated tumor cells is limited, with out-of-field recurrence being a common pattern of failure in HCC patients treated with high-dose irradiation. Atezolizumab (anti-programmed death-ligand 1; anti-PD-L1) in conjunction with bevacizumab (anti-vascular endothelial growth factor; anti-VEGF) has recently emerged as the standard first-line systemic treatment for unresectable hepatocellular carcinoma (HCC). Despite an objective response rate (ORR) of only 27%, the majority of patients succumb to HCC progression and liver failure. Our preclinical study (Hsieh et al., Science Immunology 2022) uncovered that RT, when combined with PD-L1/PD-1 blockade, induces immunogenic cell death and tumor antigen cross-presentation in antigen-presenting cells, enhancing systemic antitumor T cell responses in murine tumor models. Recent retrospective cohorts suggest that RT targeting all hepatic tumors combined with PD-L1/programmed death-1 (PD-1) blockade is associated with an improved ORR and median progression-free survival (PFS) in patients with unresectable HCC, demonstrating a favorable safety profile. The synergistic antitumor effects of this combination therapy with RT, atezolizumab, and bevacizumab have led to its increasing adoption in routine clinical practice.
This phase II non-randomized trial aims to prospectively investigate the predictive value of hyperpolarized 13C-MRI, along with comprehensive metabolomics and radiomics analyses, for immune response assessment including tumor control outcomes and toxicity in patients with HCC undergoing radiotherapy, atezolizumab, and bevacizumab.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm of hyperpolarized 13C pyruvate MRI
| Arm | Type | Receives |
|---|---|---|
| Hyperpolarized 13C pyruvate MRI | Experimental | Diagnostic Test: Hyperpolarized 13C pyruvate MRIHyperpolarized 13C pyruvate MRI before and 2-5 weeks after radiotherapy combined with atezolizumab and bevacizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Participants must have diagnosis of HCC that is deemed unsuitable for surgical resection or transplant and will undergo radiotherapy, atezolizumab, and bevacizumab. Participants may have multiple lesions with a total maximal tumor dimension of \< 20 cm, and no one lesion \> 15 cm. Diagnosis should be confirmed by at least 1 criteria listed below:
- Age ≥18 years at the time of signing informed consent document.
- ECOG performance status 0-1.
- Barcelona Clinic Liver Cancer (BCLC) stages Intermediate (B) or Advanced (C).
- Child-Pugh score 5-6 liver function within 28 days of study registration.
Key exclusion criteria (25 listed)
- Prior invasive malignancy unless disease free for a minimum of 2 years
- Prior radiotherapy to the region of the liver that would result in overlap of radiation therapy fields
- Prior selective internal radiotherapy/hepatic arterial yttrium therapy, at any time
- Untreated active hepatitis B or hepatitis C
- Moderate to severe or intractable ascites
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 |
|---|---|---|
| Hyperpolarized 13C pyruvate MRIThe subject enrolled in this trial will receive DNP-MRI scanning for two times through hyperpolarized [1-13C]pyruvate injection (~250 mM, 0.43 mL/Kg) before and 2-5 weeks after radiotherapy. | Diagnostic test | Hyperpolarized 13C pyruvate MRI |
Primary outcome
Dynamic Nuclear Polarization (DNP)
Time frame: 4 months
Dynamic Nuclear Polarization (DNP) conversion flux (pyruvate-to-lactate conversion rate [Kpl] and area under the curve [AUC]) before radiotherapy combined with atezolizumab and bevacizumab
Dynamic Nuclear Polarization (DNP)
Time frame: 4 month
Dynamic Nuclear Polarization (DNP) conversion flux (pyruvate-to-lactate conversion rate [Kpl] and area under the curve [AUC]) 2-5 weeks after radiotherapy combined with atezolizumab and bevacizumab
6 secondary outcomes
Progression free survival (PFS) by RECIST1.1
Time frame: 12 months
Local control (LC) by RECIST1.1
Time frame: 12 months
Time to progression (TTP) by RECIST1.1
Time frame: 12 months
Overall Response Rate (ORR) by RECIST1.1
Time frame: 12 months
Overall survival (OS)
Time frame: 12 months
Incidence and severity of adverse events
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2026.
- Individual participant dataSharing planned: Undecided. The sharing of individual participant data (IPD) requires IRB approval.
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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.
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 Hyperpolarized 13C pyruvate MRI in people with Hepatocellular Carcinoma (HCC), run by Chang Gung Memorial 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 20 inclusion and 25 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: looking for participants now, as of the sponsor's last update on 29 Sep 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rodney Cheng-En Hsieh, MD, PhD (+886-3-328-1200 ext. 7000, chsieh@cgmh.org.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dynamic Nuclear Polarization (DNP) (time frame: 4 months). 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 29 Sep 2026.