Trials / Recruiting

RecruitingNCT04430452

Durvalumab With/Without Tremelimumab After Palliative Hypofractionated Radiotherapy for Hepatocellular Carcinoma

Phase II Trial of Durvalumab (MEDI4736) With/Without Tremelimumab for Advanced Hepatocellular Carcinoma After Palliative Hypofractionated Radiotherapy

Status: Recruiting
Phase: Phase 2
Study type: Interventional
Enrollment: 21 (estimated)

Sponsor: Mary Feng, MD · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase II trial studies how well standard of care hypofractionated radiation therapy followed by durvalumab with or without tremelimumab works in treating patients with hepatocellular cancer (liver cancer) that has spread to other places in the body (advanced) and that is growing, spreading, or getting worse (progressing). In some patients, cancer cells and immune cells start to express signals that stop the body's immune system from killing the cancer. New drugs being developed, such as durvalumab and tremelimumab, are designed to target and block these signals and may help increase the immune response to prevent or slow down cancer growth. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may help the immune system work even better. Giving durvalumab with or without tremelimumab after radiation therapy may work better than radiation therapy alone in treating patients with liver cancer.

Detailed description

PRIMARY OBJECTIVE: I. Determine Objective Response Rate (ORR) (per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, excluding radiotherapy (RT)-treated lesions as targets) of Durvalumab (D), and D + Tremelimumab (T) after palliative RT in advanced Hepatocellular carcinoma (HCC) participants with or without progression on prior programmed death-ligand 1 (PD-L1) immune checkpoint inhibitor. SECONDARY OBJECTIVES: I. To determine the safety and tolerability of study interventions. II. Determine the efficacy of treatment interventions defined as progression-free survival (PFS), duration of response (DOR), and overall survival (OS). EXPLORATORY OBJECTIVES: I. Profile peripheral blood mononuclear cell (PBMC) immune cells and plasma samples before RT, after RT, and during D or D + T immunotherapy. II. Explore relationship between peripheral blood and PBMC immune profiles, safety/tolerability, and clinical outcomes. III. Profile immune cells in archival pre-treatment tumor tissue for all patients and on-/post-treatment tumor samples and/or non-tumor liver tissue samples when available and explore for relationship with safety/tolerability and clinical outcomes. IV. Determine incidence of tumor PD-L1 expression by immunohistochemistry (IHC) in pre-treatment archival tumor samples in all patients, and in on-/post-treatment tumor samples if repeat tumor sampling is obtained for clinical indications. V. Explore relationship between tumor PD-L1 status and clinical outcomes. VI. Explore relationship between viral hepatitis status, viral load, safety/tolerability, and clinical outcomes. VII. Measure tumor marker alpha-fetoprotein (AFP) response to immunotherapy plus RT and explore for relationship with clinical outcomes. VIII. Explore relationship between site of RT (liver, bone, other soft tissue), number of RT sites (1 or \> 1), safety/tolerability, clinical outcomes, and changes in immune cell profiles on treatment. OUTLINE: All participants receive 5-fraction RT as standard treatment for symptomatic or high-risk metastases and will be sequentially assigned to treatment Arm 1. Arm 1 will be closed after the 6th patient is enrolled. Subsequent participants will be enrolled directly into Arm 2 (progression on prior PD(L)-1 immune checkpoint inhibitor) or Arm 3 (no prior PD(L)-1 immune checkpoint inhibitor). After completing up to 2 years of treatment, treatment for participants with ongoing clinical benefit will be decided on a case-by-case basis and follow-ed up for survival endpoints for approximately 3 years after the first treatment.

Conditions

Interventions

Type	Name	Description
BIOLOGICAL	Durvalumab	Given IV
RADIATION	Hypofractionated Radiation Therapy	Undergo hypofractionated RT
BIOLOGICAL	Tremelimumab	Given IV

Timeline

Start date: 2022-02-04
Primary completion: 2028-07-31
Completion: 2029-07-31
First posted: 2020-06-12
Last updated: 2025-12-08

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT04430452. Inclusion in this directory is not an endorsement.