Actively Recruiting
Phase II Trial of Durvalumab With or Without Tremelimumab Following Palliative Hypofractionated Radiation Therapy for Advanced Hepatocellular Carcinoma
Led by Mary Feng, MD · Updated on 2025-12-08
21
Participants Needed
1
Research Sites
52 weeks
Total Duration
On this page
Sponsors
M
Mary Feng, MD
Lead Sponsor
A
AstraZeneca
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating how well standard hypofractionated radiation therapy followed by durvalumab with or without tremelimumab works in treating patients with advanced hepatocellular carcinoma (liver cancer) that has spread and is progressing. This phase II trial focuses on patients whose cancer cells and immune cells express signals that block the immune system, and these new drugs are designed to block those signals to potentially improve the immune response. Hypofractionated radiation delivers higher doses over a shorter time, possibly enhancing immune effects against cancer. All participants receive five daily radiation treatments to areas needing symptom relief or at high risk. Participants are assigned to one of three treatment groups: durvalumab alone after radiation; durvalumab combined with a single dose of tremelimumab following progression on prior PD-L1 checkpoint inhibitors; or durvalumab combined with tremelimumab for those without prior PD-L1 therapy. Treatments start within 3 to 10 days after radiation and continue every 28 days for up to two years unless disease worsens or side effects occur. During the study, participants undergo regular assessments including tumor scans to measure response by RECIST criteria, blood tests to monitor immune cells and liver function, and safety evaluations. Researchers will also analyze tumor tissue samples when available to study immune changes and treatment effects. After up to two years of treatment, ongoing benefits are evaluated case-by-case, with survival follow-up continuing for about three years from treatment start.
CONDITIONS
Brief Title
Durvalumab With/Without Tremelimumab After Palliative Hypofractionated Radiotherapy for Hepatocellular Carcinoma
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Histologically diagnosed hepatocellular carcinoma (HCC) with progression on or without prior PD-(L)1 checkpoint inhibitor immunotherapy
- Radiographic diagnosis allowed if meeting AASLD criteria for patients without prior biopsy
- At least one measurable tumor not previously treated with radiation or local therapy
- Clinical need for radiation therapy to any site
- Child Pugh score of A, B7, or B8 with other liver function criteria met
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Appropriate antiviral therapy for hepatitis B with HBV DNA PCR less than 2000 IU/mL
- Adequate blood counts and organ function as defined
- No contraindications to immune checkpoint inhibitor therapy or radiation therapy
- Age 18 years or older
- Life expectancy of at least 12 weeks
- Body weight over 30 kg (66.1 pounds)
- Women must be post-menopausal or have negative pregnancy tests if pre-menopausal, with age-specific criteria
- Use of effective contraception during study and for specified months after treatment
- Willing and able to comply with protocol and provide informed consent
You will not qualify if you...
- Prior radiation that compromises safety of further treatment
- Radiation to more than 30% of bone marrow or wide field within 4 weeks before study
- Previous treatment with CTLA-4 or PD-L1 inhibitors
- History of allogenic organ transplantation
- Severe immune-related adverse events or ongoing toxicities from prior PD-1 immunotherapy
- Major surgery or anticancer therapy within 4 weeks prior to enrollment
- Unresolved toxicities from previous treatments except certain exceptions
- Concurrent enrollment in other interventional clinical studies except follow-up
- Active or past autoimmune or inflammatory disorders except specific exceptions
- Uncontrolled illnesses including infections or serious heart, lung, or psychiatric conditions
- History of other cancers unless treated and inactive for 2 or more years
- History of leptomeningeal carcinomatosis or primary immunodeficiency
- Active infections including tuberculosis or HIV
- Recent use of immunosuppressive medications except specific low-dose or topical steroids
- Receipt of live vaccines within 30 days before treatment
- Pregnancy, breastfeeding, or unwillingness to use birth control
- Allergies to study drugs or excipients
- Prior participation in durvalumab or tremelimumab trials
- Involvement in study planning or conduct
- Any condition making the participant unsuitable in the investigator's opinion
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 5 days
Participants undergo standard of care radiation therapy over 5 daily treatments (fractions) for symptomatic or high-risk metastases.
5 visits (in-person, daily)
Duration - Up to 2 years
Participants receive immunotherapy with durvalumab alone or combined with tremelimumab starting 3 to 10 days after completing radiation therapy. Treatment cycles repeat every 28 days for up to 2 years or until disease progression or unacceptable toxicity.
Visits every 28 days for infusion and assessments
Duration - Approximately 3 years
Participants with ongoing clinical benefit after treatment are followed for survival and other long-term outcomes.
Periodic follow-up visits
Trial Site Locations
Total: 1 location
1
University of California, San Francisco
San Francisco, California, United States, 94143
Actively Recruiting
Research Team
L
Luchia Andemicael
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
3
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