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

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• Chang Gung Memorial Hospital at Linkou
  Taoyuan City, Taiwan, Taiwan Recruiting

Study contacts

• Study coordinator: Rodney Cheng-En Hsieh, MD, PhD
• Email: rodney445@gmail.com
• Phone: +886975361338

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Proton radiation with tremelimumab and durvalumab for BCLC stage B/C hepatocellular carcinoma

  This will test whether adding precise proton radiation to tremelimumab plus durvalumab helps people with unresectable BCLC stage B or C hepatocellular carcinoma.

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• STRIDE combination in advanced liver cancer: a first-line look at tremelimumab plus durvalumab

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• RBS2418 with tremelimumab and durvalumab for advanced unresectable liver cancer

  This trial will test whether adding RBS2418 to tremelimumab plus durvalumab helps adults with advanced, unresectable hepatocellular carcinoma.

  Recruiting at 4 sites Phase 2 Riboscience, LLC. · Baltimore, Maryland and 3 other locations · NCT07175441

• Celecoxib with durvalumab and tremelimumab for advanced liver cancer

  This phase II trial tests whether adding the oral drug celecoxib to the immunotherapy drugs durvalumab and tremelimumab helps people with advanced or metastatic liver cancer.

  Recruiting at 3 sites Phase 2 Emory University · Atlanta, Georgia and 3 other locations · NCT07174570

• Y-90 internal liver radiation followed by tremelimumab and durvalumab for liver cancer with portal vein thrombosis

  This will test whether Y-90 selective internal radiation (SIRT) followed by tremelimumab and durvalumab helps people with non-resectable hepatocellular carcinoma that involves the portal vein.

  Recruiting Phase 2 Center Eugene Marquis · Grenoble and 5 other locations · NCT07122089

• Radiation therapy followed by immune therapy and surgery for hepatocellular carcinoma

  This trial tests whether adding durvalumab and tremelimumab to radiation therapy before surgery helps people with resectable liver cancer.

  Recruiting Phase 3 Hamilton Health Sciences Corporation · Hamilton, Ontario and 1 other locations · NCT07027436

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.