Combining Atezolizumab and Bevacizumab with Photon Radiotherapy for Liver Cancer

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

This study is testing if combining two cancer drugs, atezolizumab and bevacizumab, with radiation therapy can help people with liver cancer that can't be surgically removed live longer and feel better.

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: NCT06339424 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of combining atezolizumab and bevacizumab with photon radiotherapy in patients with unresectable hepatocellular carcinoma (HCC). The study aims to improve patient outcomes by addressing resistance to existing treatments and enhancing overall survival rates. Participants will receive these treatments under specific eligibility criteria, including confirmed HCC diagnosis and certain liver function parameters. The trial builds on previous findings that suggest this combination may lead to better survival outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with unresectable HCC and specific liver function criteria.

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

Why it matters

Potential benefit: If successful, this approach could significantly improve survival rates for patients with unresectable hepatocellular carcinoma.

How similar studies have performed: Previous studies have shown promising results with similar combinations of therapies, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Participants must have a 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.
2. Age ≥18 years at the time of signing the 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

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 that cannot be encompassed by photon radiotherapy
7. Untreated or incompletely 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 photon radiotherapy (such as extrahepatic metastases or massive liver tumors whereby the liver constraints cannot be met for covering all sites of liver tumors.)
14. 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; Photon Radiotherapy; HCC; PD-L1; VEGF; Atezolizumab; Bevacizumab