Photon radiotherapy plus tremelimumab and durvalumab for intermediate or advanced hepatocellular carcinoma

Photon Radiotherapy Combined With Tremelimumab and Durvalumab for BCLC Stage B and C Hepatocellular Carcinoma

This trial tests whether adding targeted photon radiotherapy to tremelimumab plus durvalumab helps people with unresectable intermediate or advanced (BCLC B or C) hepatocellular carcinoma respond better to treatment.

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, Tremelimumab, durvalumab, immunotherapy
• Locations: 1 site (Taoyuan City, Taiwan)
• Trial ID: NCT06999707 on ClinicalTrials.gov

What this trial studies

This is a Phase 2 interventional trial combining photon radiotherapy with the STRIDE immunotherapy regimen (tremelimumab plus durvalumab) in patients with unresectable BCLC stage B or C hepatocellular carcinoma. The rationale is that radiotherapy can provoke immunogenic tumor cell death and improve antigen presentation, and adding CTLA-4 plus PD-L1 blockade may further boost systemic T cell responses. The trial enrolls adults with preserved liver function (Child-Pugh 5-6), ECOG 0-1, and defined tumor size limits, and will monitor clinical responses and immunologic effects during and after combined treatment. The lead site is Chang Gung Memorial Hospital, Linkou, Taiwan.

Who should consider this trial

Good fit: Adults (≥18) with unresectable HCC classified as BCLC stage B or C, ECOG 0-1, Child-Pugh score 5-6, and tumor sizes within the protocol limits are the intended participants.

Not a fit: People with decompensated liver disease, poorer performance status (ECOG >1), tumors exceeding the protocol size limits, or those eligible for curative resection/transplant are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could raise tumor response rates and improve local control and survival for people with unresectable HCC.

How similar studies have performed: Preclinical studies and retrospective clinical series suggest combining radiotherapy with immune checkpoint blockade can improve responses, but prospective randomized evidence in HCC remains limited.

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 photon 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. 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 using photon radiotherapy.)
13. 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 HCC - Hepatocellular Carcinoma; Tremelimumab; Durvalumab; Radiotherapy