Denosumab Strategy for Liver Cancer With Bone Metastases

NCT07537972 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: BONE-HCC-010
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hepatocellular Carcinoma (HCC); Bone Metastases

Keywords

Denosumab; Bone Metastases; Skeletal-Related Events; Bone Pain; PD-1 Inhibitor

Outcome Measures

Primary Outcomes (1)

• Skeletal-Related Event-Free Survival

  Skeletal-related event-free survival (SREFS) is defined as the time from randomization to the first on-study skeletal-related event or death from any cause. Skeletal-related events include pathologic fracture, spinal cord compression, radiation therapy to a bone lesion, and orthopedic surgery to a bone lesion. Malignant hypercalcemia is recorded separately as an extended bone event.

  From randomization to the first on-study skeletal-related event or death from any cause, assessed up to 24 months

Secondary Outcomes (2)

• Time to First Skeletal-Related Event

  From randomization through 24 months

• Cumulative Incidence of Skeletal-Related Events

  At 6 months and 12 months after randomization

Study Arms (2)

Early Denosumab Plus Uniform PD-1-Based Systemic Therapy

EXPERIMENTAL

Participants receive early denosumab initiated at baseline together with a locked uniform PD-1-based systemic therapy backbone, plus standard supportive care, analgesic treatment, and clinically necessary local treatment for bone metastases.

Drug: Sintilimab; Other: Delayed/Rescue Bone-Modifying Strategy

Delayed/Rescue Bone-Modifying Strategy Plus Uniform PD-1-Based Systemic Therapy

ACTIVE COMPARATOR

Participants receive the same locked uniform PD-1-based systemic therapy backbone, plus standard supportive care, analgesic treatment, and clinically necessary local treatment for bone metastases, but do not routinely receive prophylactic bone-modifying agents at baseline. Rescue bone-modifying therapy may be initiated only when predefined protocol triggers occur.

Drug: Denosumab; Drug: Sintilimab

Interventions

Denosumab DRUG

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.

Delayed/Rescue Bone-Modifying Strategy Plus Uniform PD-1-Based Systemic Therapy

Sintilimab DRUG

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.

Delayed/Rescue Bone-Modifying Strategy Plus Uniform PD-1-Based Systemic Therapy; Early Denosumab Plus Uniform PD-1-Based Systemic Therapy

Delayed/Rescue Bone-Modifying Strategy OTHER

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.

Early Denosumab Plus Uniform PD-1-Based Systemic Therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tongji Hospital: lead

Study Sites (1)

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

Wuhan, Hubei, 430030, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Denosumab; sintilimab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Zhao Huang, M.D

CONTACT

+86 13006378908; huangzhao@tjh.tjmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: This is an open-label study because denosumab administration and rescue strategy management cannot be practically masked. However, the primary bone-related endpoint, skeletal-related event adjudication, and key endpoint review will be performed by blinded independent outcome assessors.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Model Details: Participants are randomized in a 1:1 ratio to receive either early denosumab plus a locked uniform PD-1-based systemic therapy or the same locked PD-1-based systemic therapy with a delayed/rescue bone-modifying strategy.

Study Record Dates

• First Submitted: April 12, 2026
• First Posted: April 17, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 30, 2029
• Study Completion (Estimated): June 30, 2029
• Last Updated: April 17, 2026

Record last verified: 2026-04

Locations

CN (1)