Using advanced MRI to assess treatment response in liver cancer patients

Hyperpolarized 13C-MRI, Metabolomics, and Radiomics for Immune Response Prediction in Patients With Hepatocellular Carcinoma Undergoing Radiotherapy, Atezolizumab, and Bevacizumab

This study is testing a special type of MRI to see if it can help doctors understand how well new treatments are working for people with liver cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Chang Gung Memorial Hospital (Academic / other)
• Drugs / interventions: atezolizumab, bevacizumab, radiation, immunotherapy
• Locations: 1 site (Taoyuan City)
• Trial ID: NCT06605664 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of hyperpolarized carbon-13 MRI to evaluate metabolic changes in patients with hepatocellular carcinoma (HCC) undergoing radiotherapy combined with atezolizumab and bevacizumab. The study aims to establish quantitative imaging biomarkers that can predict treatment responses, addressing a significant gap in the management of HCC. By leveraging the unique metabolic profile of HCC, the trial seeks to provide real-time insights into tumor metabolism and treatment efficacy. Participants will be closely monitored to assess the effectiveness of this innovative imaging technique in a clinical setting.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a diagnosis of HCC that is not suitable for surgical intervention and who will receive radiotherapy along with atezolizumab and bevacizumab.

Not a fit: Patients with early-stage HCC who are eligible for surgical resection or transplant may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to improved treatment strategies and outcomes for patients with hepatocellular carcinoma.

How similar studies have performed: While the use of hyperpolarized MRI in other solid tumors has shown promise, its application in hepatocellular carcinoma is still being explored and is considered novel.

Eligibility criteria

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:

   * Histologically 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 informed consent document.
3. ECOG performance status 0-1.
4. Barcelona Clinic Liver Cancer (BCLC) stages Intermediate (B) or Advanced (C).
5. Child-Pugh score 5-6 liver function within 28 days of study registration.
6. Documented virology status of hepatitis B virus (HBV), as confirmed by screening HBV serology test.
7. Documented virology status of hepatitis C 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

   * 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
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:

1. Prior invasive malignancy 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 hepatitis B or hepatitis C
5. Moderate to severe or intractable ascites
6. Presence of distant metastases
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 childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
10. Prior solid organ transplantation.
11. 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.
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 HIV 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.

Where this trial is running

Taoyuan City

• Chang Gung Memorial Hospital at Linkou — Taoyuan City, Taiwan (Recruiting)

Study contacts

• Study coordinator: Rodney Cheng-En Hsieh, MD, PhD

Conditions Hepatocellular Carcinoma; Hyperpolarized 13C-MRI; HCC; Radiotherapy; Metabolomics; Atezolizumab; Bevacizumab