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Hepatocellular Carcinoma (HCC)Phase 2NCT07537972

Denosumab Strategy for Liver Cancer With Bone Metastases

A Phase 2 study testing Denosumab, Sintilimab and Delayed/Rescue Bone-Modifying Strategy in people with Hepatocellular Carcinoma (HCC) and Bone Metastases, run by Tongji Hospital at 1 site in China.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Denosumab, Sintilimab and Delayed/Rescue Bone-Modifying Strategy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteChina
Study dates
1 May 2026to 30 Jun 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

China1 site
  • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

    Wuhan, Hubei, 430030

Other trials in China

About this study

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

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.

Read the detailed description

This is a single-center, prospective, randomized, open-label, blinded-endpoint (PROBE) exploratory phase 2 strategy study in patients with hepatocellular carcinoma (HCC) and radiologically or pathologically confirmed bone metastases. A total of 50 participants will be randomized in a 1:1 ratio to either early denosumab plus a locked uniform PD-1-based systemic therapy or the same PD-1-based systemic therapy with a delayed/rescue bone-modifying strategy.

The study is designed to evaluate whether an early denosumab strategy can improve bone-related clinical outcomes in HCC with bone metastases. The key clinical question is not whether denosumab improves short-term intrahepatic radiographic response, but whether early RANKL inhibition can reduce or delay skeletal-related events, delay pain worsening, and improve quality of life when added to a uniform PD-1-based systemic therapy backbone.

The PD-1-based systemic therapy backbone must be locked before enrollment of the first participant and remain consistent throughout the study. Both study arms receive the same locked systemic regimen, standard supportive care, analgesic therapy, and clinically necessary local treatment for bone metastases. The only protocol-defined treatment difference between the two arms is whether denosumab is started at baseline.

Participants randomized to the experimental arm will receive denosumab 120 mg subcutaneously every 4 weeks, with correction of hypocalcemia before treatment initiation and calcium/vitamin D supplementation as indicated. Participants randomized to the control arm will not routinely receive prophylactic bone-modifying agents at baseline. Rescue bone-modifying therapy may be initiated when predefined triggers occur, such as impending or actual pathologic fracture, spinal cord compression or worsening spinal instability, worsening bone pain despite standard management, rapidly progressive bone destruction judged to substantially increase skeletal-related event risk, or malignant hypercalcemia.

The primary endpoint is skeletal-related event-free survival (SREFS), 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 will be recorded separately as an extended bone event. A fixed-time key analysis is planned at Month 6, with continued follow-up through Month 24.

Secondary endpoints include time to first skeletal-related event; cumulative incidence of skeletal-related events at 6 and 12 months; bone pain outcomes measured by the Brief Pain Inventory; time to pain progression; time to analgesic escalation; quality-of-life outcomes using EORTC QLQ-C30 with optional QLQ-BM22 or QLQ-HCC18; intrahepatic objective response rate and intrahepatic disease control rate at Week 12; intrahepatic progression-free survival, overall progression-free survival, and overall survival; incidence and severity of adverse events; and the frequency and timing of rescue bone-modifying treatment in the control arm.

Baseline imaging must be completed within 14 days before randomization. Tumor imaging is recommended every 8 weeks during the first 6 months and every 12 weeks thereafter until disease progression, death, loss to follow-up, or study end. Pain assessments are performed at baseline, Week 4, Week 8, Month 3, and every 4 weeks through Month 12, then every 8 to 12 weeks during follow-up. The study includes independent blinded endpoint adjudication for skeletal-related events and a Data and Safety Monitoring Board for ongoing safety oversight.

Being tested
Denosumab, Sintilimab, Delayed/Rescue Bone-Modifying Strategy
Keywords
Denosumab, Bone Metastases, Skeletal-Related Events, Bone Pain, PD-1 Inhibitor
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DenosumabDrug

    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.

  • SintilimabDrug

    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 StrategyOther

    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.

Study groups in NCT07537972
Study groupRoleWhat they receive
Early Denosumab Plus Uniform PD-1-Based Systemic TherapyExperimentalParticipants 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.
Receives: Drug: Sintilimab; Other: Delayed/Rescue Bone-Modifying Strategy
Delayed/Rescue Bone-Modifying Strategy Plus Uniform PD-1-Based Systemic TherapyActive comparatorParticipants 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.
Receives: Drug: Denosumab; Drug: Sintilimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (2)
  1. Time to First Skeletal-Related Event

    Time from randomization to the first skeletal-related event.

    Measured: From randomization through 24 months

  2. Cumulative Incidence of Skeletal-Related Events

    Cumulative incidence of protocol-defined skeletal-related events at 6 and 12 months.

    Measured: At 6 months and 12 months after randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Apr 2026
  2. Study start1 May 2026 (estimated)
  3. Primary completion30 May 2029 (estimated)
  4. Study completion30 Jun 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07537972
Sponsor's protocol ID
BONE-HCC-010
Status last verified
Apr 2026
First submitted
12 Apr 2026
Last updated
17 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Denosumab, Sintilimab and Delayed/Rescue Bone-Modifying Strategy in people with Hepatocellular Carcinoma (HCC) and Bone Metastases, run by Tongji Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 17 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Zhao Huang, M.D (+86 13006378908, huangzhao@tjh.tjmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Skeletal-Related Event-Free Survival (time frame: From randomization to the first on-study skeletal-related event or death from any cause, assessed up to 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2026.

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