Clinical Research Directory

Browse clinical research sites, groups, and studies.

Sites Groups Studies

Back to Studies

NOT YET RECRUITING

NCT07537972

PHASE2

Denosumab Strategy for Liver Cancer With Bone Metastases

Sponsor: Tongji Hospital

View on ClinicalTrials.gov

Summary

This study will evaluate whether starting denosumab early, together with a locked uniform PD-1-based systemic therapy, can reduce skeletal-related events and delay worsening bone pain compared with a delayed/rescue bone-modifying strategy in patients with hepatocellular carcinoma and bone metastases. Participants will be randomly assigned in a 1:1 ratio to receive either early denosumab plus the same PD-1-based systemic therapy or the same systemic therapy with no routine prophylactic bone-modifying agent at baseline and rescue treatment only when predefined triggers occur. The primary outcome is skeletal-related event-free survival. Secondary outcomes include time to first skeletal-related event, pain outcomes, quality of life, intrahepatic antitumor activity at Week 12, progression-free survival, overall survival, and safety.

Official title: Early Denosumab Plus a Uniform PD-1-Based Systemic Therapy Versus Delayed/Rescue Bone-Modifying Strategy in Hepatocellular Carcinoma With Bone Metastases: A Single-Center Prospective Randomized Controlled Exploratory Study

Key Details

Gender

All

Age Range

18 Years - 75 Years

Study Type

INTERVENTIONAL

Enrollment

Start Date

2026-05-01

Completion Date

2029-06-30

Last Updated

2026-04-17

Healthy Volunteers

Conditions

Hepatocellular Carcinoma (HCC)Bone Metastases

Interventions

DRUG

Denosumab

Denosumab 120 mg administered as a subcutaneous injection every 4 weeks in the upper arm, upper thigh, or abdomen. Pre-existing hypocalcemia must be corrected before treatment initiation. Calcium and vitamin D supplementation should be given as needed to prevent or treat hypocalcemia.

DRUG

Sintilimab

The prespecified PD-1 inhibitor component of the locked uniform systemic therapy backbone used in both study arms. Replace this placeholder with the exact generic name, route, dose, and schedule before final submission.

OTHER

Delayed/Rescue Bone-Modifying Strategy

No routine prophylactic bone-modifying agent is given at baseline. Rescue bone-modifying therapy may be started when predefined triggers occur, including impending or actual pathologic fracture, spinal cord compression or worsening spinal instability, worsening bone pain despite standard management, rapidly progressive bone destruction judged to increase skeletal-related event risk, or malignant hypercalcemia.

Inclusion Criteria: * Age 18 to 75 years * Hepatocellular carcinoma confirmed by imaging and/or histology according to current institutional diagnostic standards * Bone metastasis confirmed by CT, MRI, bone scintigraphy, PET-CT, or pathology * ECOG performance status 0 to 1 * Child-Pugh class A or stable Child-Pugh B7 judged suitable for systemic treatment * At least 1 measurable intrahepatic lesion at baseline and planned initiation of a PD-1 inhibitor-based systemic therapy * Estimated life expectancy of at least 3 months * Adequate organ function according to protocol-defined laboratory criteria * Corrected serum calcium within the normal range, or corrected to protocol-defined range after calcium/vitamin D supplementation * Completed baseline oral/dental risk assessment and willingness to avoid nonessential invasive dental procedures during the study * Written informed consent and willingness to comply with study visits, questionnaires, sample collection, and follow-up Exclusion Criteria: * Prior treatment with PD-1, PD-L1, CTLA-4, or other immune checkpoint inhibitors * Receipt of denosumab or intravenous/oral bisphosphonates for tumor-related bone disease within 6 months before randomization * Uncorrected hypocalcemia or severe vitamin D deficiency that cannot be corrected promptly * Current or prior osteonecrosis of the jaw, jaw osteomyelitis, or high-risk dental condition requiring near-term extraction, implantation, or other invasive dental procedures that cannot be deferred * Active autoimmune disease or need for systemic immunosuppressive treatment, except for low-risk conditions judged acceptable by the investigator * Life-threatening bone complication within 4 weeks before randomization that is not stabilized, including unresolved spinal cord compression or clinically significant spinal instability * Active infection, including uncontrolled bacterial or fungal infection, active tuberculosis, or other condition judged unsafe for systemic treatment * Symptomatic or uncontrolled central nervous system metastases * Pregnancy or breastfeeding, or refusal to use effective contraception when applicable * Known severe hypersensitivity to denosumab or any study-related treatment component * Another active malignancy, poor compliance, or any condition judged by the investigator to make study participation unsuitable

Locations (1)

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China