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

Официальное название

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

Обзор

Tremelimumab plus durvalumab (the STRIDE regimen) is an approved first-line therapy for unresectable hepatocellular carcinoma (HCC); however, it demonstrates limited efficacy, with an objective response rate (ORR) of only 20.1%. Radiation therapy (RT) is highly effective in controlling localized solid tumors and has become an integral component of the treatment algorithm for unresectable HCC. Preclinical studies have shown that combining RT with PD-L1/PD-1 blockade promotes immunogenic cell death and enhances antigen presentation by dendritic cells, thereby boosting systemic T cell-mediated antitumor responses in mouse models. The addition of CTLA-4 inhibition further enhances antigen cross-priming following RT. Recent retrospective data also indicate that combining RT with immune-oncology agents is associated with improved overall survival and prolonged time to progression compared to RT or immunotherapy alone. However, the clinical benefit and immunologic impact of combining RT with tremelimumab and durvalumab have not yet been evaluated in prospective clinical trials for unresectable HCC. This phase II, single-arm clinical trial aims to assess the safety, efficacy, and immunologic effects of combining proton RT with tremelimumab and durvalumab in patients with unresectable HCC.

Вмешательства

• Лучевая терапия Photon radiotherapy
  * 39.6-72.6 Gy in 22 fractions for tumors ≤1 cm from hepatic hilum, bowel, and heart. * 30-66 Gy in 10 fractions for tumors \>1 cm from hepatic hilum, bowel, and heart. * 27.5-50 Gy in 5 fractions using stereotactic body radiation therapy (SBRT) techniques
• Препарат Tremelimumab
  Tremelimumab 300 mg will be administered as an IV infusion for one dose
• Препарат Durvalumab
  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.

Первичные конечные точки

• Progression free survival [Срок оценки: 12 months]

Вторичные конечные точки (5)

• Local control [Срок оценки: 12 months]
• Time to progression [Срок оценки: 12 months]
• Overall Response Rate [Срок оценки: 12 months]
• Overall survival [Срок оценки: 12 months]
• Incidence and severity of adverse events [Срок оценки: 12 months]

Критерии участия

Критерии включения

• 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
• 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

Критерии исключения

• 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 photon 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
• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
• Prior solid organ transplantation.
• 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.
• 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.)
• Known HIV infection.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Тайвань · 1 центр

• Chang Gung Memorial Hospital at Linkou — Taoyuan City

Идентификаторы

NCT: NCT06999707 · 202500671A3

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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