Combining Atezolizumab and Bevacizumab with Proton Radiotherapy for Liver Cancer

Investigation of Antitumor Immune Response in Patients With Unresectable Hepatocellular Carcinoma Undergoing Proton Radiotherapy Combined With Atezolizumab and Bevacizumab

This study is testing if combining two cancer-fighting drugs with a type of targeted radiation can help people with advanced liver cancer that can't be surgically removed feel better and live longer.

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: radiation, Atezolizumab, bevacizumab
• Locations: 1 site (Taoyuan City, Taiwan)
• Trial ID: NCT06133062 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of combining Atezolizumab and Bevacizumab with proton radiotherapy in patients with unresectable hepatocellular carcinoma (HCC). The approach aims to enhance the objective response rate and progression-free survival by targeting the cancer with both immunotherapy and localized radiation. Participants must have a confirmed diagnosis of HCC that cannot be surgically removed, and the study will assess the safety and efficacy of this combined treatment strategy. The trial is designed to address the limitations of current therapies and improve outcomes for patients facing advanced liver cancer.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with unresectable hepatocellular carcinoma and specific liver function criteria.

Not a fit: Patients with resectable liver tumors or those with severe liver dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates and quality of life for patients with unresectable liver cancer.

How similar studies have performed: Previous studies have shown promising results with similar combinations of immunotherapy and radiation in treating unresectable HCC, suggesting potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

* Participants must have diagnosis of HCC that is deemed unsuitable for surgical resection or transplant. 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 criterion 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).
* 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

Exclusion Criteria:

* 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 that cannot be encompassed by proton radiotherapy
* 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 \[ULV/SLV \>40%\] cannot be met for covering all sites of liver tumors using proton radiotherapy.)
* Known HIV infection.

Where this trial is running

Taoyuan City, Taiwan

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

Study contacts

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

Conditions Hepatocellular Carcinoma Non-resectable; Proton radiotherapy; HCC; PD-L1; VEGF; Atezolizumab; Bevacizumab