ClinicalTrials.gg
RecruitingNCT06605664Updated Sep 29, 2026

Hyperpolarized 13C-MRI in Patients With Hepatocellular Carcinoma Undergoing Radiotherapy, Atezolizumab, and Bevacizumab

A Phase 2 interventional study of Hyperpolarized 13C pyruvate MRI in Hepatocellular Carcinoma (HCC), sponsored by Chang Gung Memorial Hospital. Recruiting at 1 site in Taiwan. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-29.

Sponsored by Chang Gung Memorial Hospital · Phase 2, Interventional, and Diagnostic

From the registry’s dates

  • Started May 2025; still recruiting 1 year 6 months later.
Updated Sep 29, 20261 site added1 site removedGo to Updates ↓

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Phase
Phase 2
Study type
Interventional
Enrollment
45
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Where this study stands

Counted across the records on this site · 2026-11-15

Among 18 studies in Carcinoma, Hepatocellular by Chang Gung Memorial Hospital — 10 open to participants now, 11 under way, none of them phase 3. Carcinoma, Hepatocellular · Chang Gung Memorial Hospital.

Planned enrollment
5th of 15
45 · median 45
Started
2025
with 2 others
Phase 2
10 of 18
7 open now
Primary completion
2029-06
later than 8 of 10 live
Registered
14th of 18
by date

Among the 18 studies in Carcinoma, Hepatocellular by Chang Gung Memorial Hospital, this one is the 5th largest by planned enrollment of the 15 interventional ones that give a count, is one of 3 that started in 2025, is one of 10 in phase 2, reaches primary completion later than 8 of the 10 other live ones, and was the 14th registered.

Carcinoma, Hepatocellular

3,650 studies on the registry are indexed under Carcinoma, Hepatocellular; 1,062 are open to participants now.

Browse Carcinoma, Hepatocellular studies →

Open to participants now

10 of the 18 studies in Carcinoma, Hepatocellular by Chang Gung Memorial Hospital are open now, in 1 country. Recruiting first, the newest first:

4 more — sign in →

By country, each count listing its studies:

All 10 open studies →

Where they have run

Who these studies take

Of the 737 Carcinoma, Hepatocellular studies recruiting now, 382 (52%) set no upper age limit and 249 (34%) stop at 75 or younger; 31 take children under 18; 31 take healthy volunteers.

This study: 18 Years and older · all sexes · no healthy volunteers.

The full table on the hub →

This tab as a report to print or save as PDF → With an account.

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Watch this landscapeDownload CSVNarrow it in search →With an account: a weekly mail of what changed among 18 studies in Carcinoma, Hepatocellular by Chang Gung Memorial Hospital, or all of them as a file.
02

Study 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. 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.

03

Conditions studied

  • Hepatocellular Carcinoma (HCC)

Keywords

  • Hyperpolarized 13C-MRI
  • HCC
  • Radiotherapy
  • Metabolomics
  • Atezolizumab
  • Bevacizumab
04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. 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:

    • or cytologically proven diagnosis of HCC.
    • Typical arterial enhancement and delayed washout on multiphasic CT or MRI.
  2. Age ≥18 years at the time of signing document.
  3. performance status 0-1.
  4. Barcelona Clinic Liver Cancer (BCLC) stages Intermediate (B) or Advanced (C).
  5. score 5-6 liver function within 28 days of study registration.
  6. Documented virology status of virus (HBV), as confirmed by screening HBV serology test.
  7. Documented virology status of virus (HCV), as confirmed by screening HCV serology test.
  8. Ability to understand and the willingness to sign a written informed consent document
  9. Adequate bone marrow, liver, and renal function within 4 weeks before study registration

    • ≥ 9.0 g/dL
    • (ANC) ≥ 1,000/mm3
    • count ≥ 50,000/μL
    • Total \< 2.5 mg/dL
    • Serum albumin >2.8 g/dL
    • (ALT) and aspartate aminotransferase (AST) ≤ 3 × (ULN)
    • ≤ 6 seconds prolonged
    • Serum creatinine ≤ 1.5 mg/dL
  10. 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.

Exclusion criteria

Exclusion Criteria:

  1. Prior invasive unless disease free for a minimum of 2 years
  2. Prior radiotherapy to the region of the liver that would result in overlap of radiation therapy fields
  3. Prior selective internal radiotherapy/hepatic arterial yttrium therapy, at any time
  4. Untreated active or
  5. Moderate to severe or intractable ascites
  6. Presence of distant
  7. Untreated or incomplete treated esophageal or gastric varices
  8. 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
  9. Pregnancy or women of and men who are sexually active and not willing/able to use medically acceptable forms of
  10. Prior solid organ transplantation.
  11. Prior or active 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.
  12. Prior or active thrombotic or bleeding disorders, hemoptysis, cerebral vascular accident, significant cardiac disease (ischemic or congestive heart failure), or gastrointestinal perforation.
  13. 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.)
  14. Known infection.
  15. 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.
  16. 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.
  17. 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.
  18. Individuals who are allergic to hyperpolarized 13C pyruvate, atezolizumab, bevacizumab, or any ingredients contained in these medications.
Terms in these criteria, in plain language(19)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Histologically or cytologically confirmed

The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).

Your pathology report is the document that shows this.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

ECOG performance status

A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.

0
Fully active, no restrictions.
1
Limited in strenuous activity, but walking and able to do light work, such as housework or office work.
2
Walking and able to look after yourself, but unable to work; up and about more than half of waking hours.
3
Able to look after yourself only in part; in bed or a chair more than half of waking hours.
4
Unable to look after yourself at all; in bed or a chair all day.

Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.

Child-Pugh class

A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

Hepatitis C tests

Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.

After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

INR, PT and aPTT (clotting tests)

Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.

Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Autoimmune disease

A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.

Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

05

Study design

Phase
Phase 2
Primary purpose
Diagnostic
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
45 participants (estimated)

Study arms

  • Experimental
    Hyperpolarized 13C pyruvate MRI

    Hyperpolarized 13C pyruvate MRI before and 2-5 weeks after radiotherapy combined with atezolizumab and bevacizumab

    Diagnostic Test: Hyperpolarized 13C pyruvate MRI

Interventions

  • Diagnostic testHyperpolarized 13C pyruvate MRI

    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.

This study also gives Atezolizumab. No intervention listed here names it: that was found by reading the record.

06

What researchers measure

Primary outcomes

  1. 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

    Time frame: 4 months

  2. 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

    Time frame: 4 month

Secondary outcomes

  1. 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

    Time frame: 12 months

  2. 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

    Time frame: 12 months

  3. 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

    Time frame: 12 months

  4. Overall Response Rate (ORR) by RECIST1.1

    ORR is defined as a complete or partial response according to RECIST1.1

    Time frame: 12 months

  5. Overall survival (OS)

    OS is defined as the time from signing the informed consent to death from any cause.

    Time frame: 12 months

  6. Incidence and severity of adverse events

    Adverse events will be graded using CTCAE v5

    Time frame: 12 months

Other outcomes

  1. Change in myeloid-derived suppressor cell (MDSC) level in peripheral blood

    We will measure the level of Lin- HLA-DR- CD11b+ MDSCs in peripheral blood using flow cytometry before and 2-5 weeks after radiotherapy.

    Time frame: 4 months

07

Study locations

1 of 1 sites recruiting
  • Chang Gung Memorial Hospital at Linkou
    Taoyuan City, Taiwan 333, Taiwan
    Recruiting
    • Rodney Cheng-En Hsieh, MD, PhD · Contactrodney445@gmail.com · +886-3-328-1200
    • Rodney Cheng En HSIEH, MD, PhD · Principal investigator
08

References and documents

Individual participant data

Plan to share: Undecided — The sharing of individual participant data (IPD) requires IRB approval.

No publications or documents are linked to this record.

09

Timeline

1 registry update since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Started May 2025 (actual). Primary completion is estimated for Jun 2029, 49 months after the start.

Of 348 non-industry phase 2 interventional studies under Carcinoma, Hepatocellular, half reached primary completion within 47 months of starting (the median), counting those still running; a quarter within 33 and three quarters within 78. This study's planned 49 months is close to that.

Counting every sponsor, half of 428 studies reached it within 43 months; a quarter within 30 and three quarters within 71.

How these figures are worked out, and which studies are left out of them.

Registered
Sep 18, 2024
First posted
Sep 20, 2024
StartActual
May 1, 2025
Primary completionEst.
Jun 30, 2029
CompletionEst.
Sep 30, 2031
Last update
Sep 29, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
Sites
1 site added, 1 site removed
Show site
  • Chang Gung Memorial Hospital at Linkou · Taoyuan City, Taiwan
Show 1 removed
  • Chang Gung Memorial Hospital at Linkou · Taoyuan City, Taiwan
Sep 29, 2026
Show all 1 update
  1. Sep 29, 2026
    1 site added, 1 site removed
    Show site
    • Chang Gung Memorial Hospital at Linkou · Taoyuan City, Taiwan
    Show 1 removed
    • Chang Gung Memorial Hospital at Linkou · Taoyuan City, Taiwan
    + 2 other changes: index terms and verification date

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT06605664
Responsible party
Cheng-En Hsieh (Attending Physician, Chang Gung Memorial Hospital) — Principal investigator
First posted
Sep 20, 2024
Start date
May 1, 2025
Primary completion
Jun 30, 2029 (estimated)
Completion
Sep 30, 2031 (estimated)
Last update
Sep 29, 2026

Study contacts

Rodney Cheng-En Hsieh, MD, PhD
Contact
chsieh@cgmh.org.tw
+886-3-328-1200 ext. 7000

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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