Proton beam therapy combined with Tecentriq and Avastin for liver cancer with portal vein invasion

Proton Beam Radiotherapy Followed by Tecentriq and Avastin for Primary Liver Cancer With Vp2-4 Portal Vein Invasion: PORTAL Study

This study is testing if combining proton beam therapy with two medications, Tecentriq and Avastin, can help people with advanced liver cancer that has spread to the portal vein live longer and feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 63 (estimated)
• Ages: 20 Years and up
• Sex: All
• Sponsor: Samsung Medical Center (Academic / other)
• Drugs / interventions: chemotherapy, atezolizumab, bevacizumab
• Locations: 1 site (Seoul)
• Trial ID: NCT05625893 on ClinicalTrials.gov

What this trial studies

This phase 2 clinical trial investigates the effectiveness and safety of combining proton beam therapy with atezolizumab and bevacizumab in patients with stage 3 or higher hepatocellular carcinoma who have portal vein invasion. The study aims to assess progression-free survival as the primary endpoint, while secondary endpoints include overall survival, time to progression, objective response rate, disease control rate, and time to local disease progression. Participants must have measurable intrahepatic viable HCC lesions and meet specific eligibility criteria related to their health status and liver function.

Who should consider this trial

Good fit: Ideal candidates are adults aged 20 and older with confirmed hepatocellular carcinoma and portal vein tumor thrombosis.

Not a fit: Patients with Child-Pugh class B or C liver function or those who have previously undergone systemic therapy for HCC may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment approach could improve survival rates and disease management for patients with advanced liver cancer.

How similar studies have performed: While this approach is innovative, similar studies combining targeted therapies with radiotherapy have shown promise in other cancer types, suggesting potential for success.

Eligibility criteria

Inclusion Criteria:

* Patients with HCC meeting all of following criteria;

  1. Histologically or radiologically confirmed hepatocellular carcinoma based on the guidelines of the Korean Liver Cancer Association-National Cancer Center 2022
  2. Age \>= 20
  3. Vp2-4 portal vein tumor thrombosis diagnosed by dynamic enhanced computed tomography (CT) or maganetic resonance images (MRI) with below finding 1) an intraluminal filling defect adjacent to the primary tumor in Vp2-4 portal vein 2) an enhancement of the filling defect on arterial phase and a washout on portal/delayed phases.
  4. Signed written informed consent
  5. at least one or more measurable intrahepatic viable HCC lesions
  6. Child-Pugh class A within 2 weeks from screening for study registration
  7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 within 2 weeks from screening for study registration
  8. Life expectancy of at least 16 weeks
  9. adequate bone marrow and liver function within 2 weeks from screening for 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) ≤ 5 × upper limit of normal (ULN)

                 * Prothrombin time in INR ≤ 1.8 × ULN

                   * Serum creatinine ≤ 1.5 mg/dL
  10. Women of childbearing potential and men must agree to use highly efficient contraception since signing of the informed consent form until at least 6 months (women) and 7 months (men) after the last study drug administration
  11. If other selection conditions are satisfied and the exclusion criteria are not met, registration is possible even in case of N1 or M1.
  12. Registration is possible even in the case of hepatic vein tumor infiltration if other selection conditions are satisfied and the exclusion criteria are not met
  13. no limitation according to the size and number of tumors in the liver.

Exclusion Criteria:

Patients with HCC meeting all of following criteria;

1. previous history of systemic treatment for HCC (If systemic treatment for HCC has been performed at least once, it will not be enrolled in this study.) However, registration is permitted if the previous systemic treatment is for adjuvant purposes or treatment for other cancers. Also allowed if previous HCC treatment is local treatment. However, cases with a history of previous upper abdominal radiotherapy (including proton therapy and heavy particle therapy) are excluded.
2. any type of anticancer agent (including investigational) within 2 weeks before enrollment
3. Having active brain metastasis or leptomeningeal metastasis need surgery or steroid therapy
4. Moderate to severe or intractable ascites
5. A history or presence of hepatic encephalopathy
6. Presence of active bacterial infection
7. Untreated active chronic hepatitis B or active hepatitis C
8. History of portal hypertension with bleeding within the past 6 months
9. Prior liver transplant
10. Uncontrolled severe medical comorbidity
11. unhealed wound
12. uncontrolled electrolyte imbalance
13. Non-interruptible therapeutic use of anticoagulants or thrombolytics
14. History of uncontrolled or autoimmune disease, or immunocompromised
15. interstitial lung disease
16. Other malignant disease (a history of treated malignancy -other than HCC- is allowable if the patient's malignancy has been in complete remission, off chemotherapy and without additional surgical intervention, during the preceding two years)
17. Mentally retarded/medically incapable of consent

Where this trial is running

Seoul

• Samsung Medical Center — Seoul, Korea, Republic of (Recruiting)

Study contacts

• Principal investigator: Jeong Il Yu, MD, PhD — Samsung Medical Center
• Study coordinator: Jeong Il Yu, MD, PhD

Conditions Hepatocellular Carcinoma; Portal Vein Thrombosis