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

NCT ID: NCT06999694

Last Updated: 2025-09-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-22
• Study Completion Date: 2033-05-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Proton radiotherapy combined with Tremelimumab and Durvalumab

Patients undergo proton radiotherapy combined with Tremelimumab and Durvalumab.

Group Type: EXPERIMENTAL

Proton radiotherapy

Intervention Type: 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.

Tremelimumab

Intervention Type: DRUG

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

Durvalumab

Intervention Type: 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.

Interventions

Proton radiotherapy

• 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.

Intervention Type: RADIATION

Tremelimumab

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

Intervention Type: DRUG

Durvalumab

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.

Intervention Type: DRUG

Other Intervention Names

Imjudo

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

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 proton radiotherapy

7. Untreated or incomplete 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 proton radiotherapy (such as extrahepatic metastases or massive liver tumors whereby the liver constraints cannot be met for covering all sites of liver tumors using proton radiotherapy.)

14. Known HIV infection.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chang Gung Memorial Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Chang Gung Memorial Hospital at Linkou

Taoyuan, Taiwan, Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Rodney Cheng-En Hsieh, MD, PhD

Role: CONTACT

rodney445@gmail.com

+88633281200 ext. 7000

Facility Contacts

Rodney Cheng-En Hsieh, MD, PhD

Role: primary

rodney445@gmail.com

+886-3-328-1200 ext. 7000

Other Identifiers

202500583A3

Identifier Type: -

Identifier Source: org_study_id