Proton Radiotherapy Plus Tremelimumab/Durvalumab for BCLC Stage B and C HCC

NCT06999694 | Recruiting Phase 2

• 1 other identifier: 202500583A3
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

HCC - Hepatocellular Carcinoma; Durvalumab; Tremelimumab; Proton Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Progression free survival is defined as the time from signing the informed consent to the first occurrence of disease progression or death from any cause (whichever occurs first) according to RECIST1.1

  12 months

Secondary Outcomes (5)

• Local control

  12 months

• Time to progression

  12 months

• Overall Response Rate

  12 months

• Overall survival

  12 months

• Incidence and severity of adverse events

  12 months

Study Arms (1)

Proton radiotherapy combined with Tremelimumab and Durvalumab

EXPERIMENTAL

Patients undergo proton radiotherapy combined with Tremelimumab and Durvalumab.

Radiation: Proton radiotherapy; Drug: Tremelimumab; Drug: Durvalumab

Interventions

Proton radiotherapy RADIATION

* 72.6 CGE in 22 fractions for tumors ≤1 cm from the hepatic hilum, bowel, and heart. * 66 CGE in 10 fractions for tumors \>1 cm from the hepatic hilum, bowel, and heart.

Proton radiotherapy combined with Tremelimumab and Durvalumab

Tremelimumab DRUG

Tremelimumab 300 mg will be administered as an IV infusion for one dose

Also known as: Imjudo

Proton radiotherapy combined with Tremelimumab and Durvalumab

Durvalumab DRUG

Durvalumab 1500 mg will be administered as an IV infusion every 4 weeks. Treatment Duration Guidelines: * Complete Response (CR): Patients who achieve a CR within one year of treatment will continue durvalumab for a total duration of two years. * Partial Response (PR): Patients who achieve a PR should continue durvalumab until achieving CR, disease progression (PD), or for a total duration of two years. * Stable Disease (SD): Patients with SD will receive duvalumab for a total of 6 doses.

Proton radiotherapy combined with Tremelimumab and Durvalumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead

Study Sites (1)

Chang Gung Memorial Hospital at Linkou

Taoyuan, Taiwan, 333, Taiwan

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

tremelimumab; durvalumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Central Study Contacts

Rodney Cheng-En Hsieh, MD, PhD

CONTACT

+88633281200; rodney445@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2025
• First Posted: May 31, 2025
• Study Start: May 22, 2025
• Primary Completion (Estimated): May 31, 2030
• Study Completion (Estimated): May 31, 2033
• Last Updated: September 10, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)