Proton Radiotherapy Plus Tremelimumab/Durvalumab for BCLC Stage B and C HCC
Trial Parameters
Brief Summary
Tremelimumab plus durvalumab (STRIDE regimen) is an approved first-line therapy for unresectable hepatocellular carcinoma (HCC), yet it shows limited efficacy with an ORR of only 20.1%. Proton radiotherapy (RT), known for its precision and tissue-sparing advantages, has demonstrated improved survival outcomes and reduced toxicity compared to X-ray RT. Retrospective data suggest that combining proton RT with immune checkpoint inhibitors yields a promising ORR of 61.5%. Preclinical studies further support enhanced antitumor immunity when RT is combined with PD-L1 and CTLA-4 blockade. This phase II, single-arm clinical trial aims to evaluate the safety, efficacy, and immunologic effects of combining proton RT with tremelimumab and durvalumab in patients with unresectable HCC.
Eligibility Criteria
Inclusion Criteria: 1. 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. 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