Clinical trial · Interventional
Denosumab Strategy for Liver Cancer With Bone Metastases
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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Bone Metastases | — | UNRESOLVED | — |
| Hepatocellular Carcinoma (HCC) | Hepatocellular Carcinoma | ONTOLOGY_EXACT | 0.85 |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Delayed/Rescue Bone-Modifying Strategy | Other | — | UNRESOLVED |
| Denosumab | Drug | Denosumab | ALIAS |
| Sintilimab | Drug | Sintilimab | ALIAS |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Early Denosumab Plus Uniform PD-1-Based Systemic Therapy
- description
- 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.
- interventionNames
- Drug: Sintilimab
- Other: Delayed/Rescue Bone-Modifying Strategy
- type
- ACTIVE_COMPARATOR
- label
- Delayed/Rescue Bone-Modifying Strategy Plus Uniform PD-1-Based Systemic Therapy
- description
- 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.
- interventionNames
- Drug: Denosumab
- Drug: Sintilimab
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 75 Years
Show eligibility criteria text
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
References
Publications (0)
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