Health TrialsbyHealthPanel

Denosumab Strategy for Liver Cancer With Bone Metastases

ConditionsHepatocellular Carcinoma (HCC)Bone Metastases
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorTongji Hospital

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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.

  • 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

    Other intervention

    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.

Treatment groups

50 Participants
are divided into 2 treatment groups
Group A: Early Denosumab Plus Uniform PD-1-Based Systemic TherapyExperimental treatment 2 interventions
Group B: Delayed/Rescue Bone-Modifying Strategy Plus Uniform PD-1-Based Systemic TherapyActive comparator 2 interventions

Trial outcomes

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.

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

Secondary outcomes

1

Time to First Skeletal-Related Event

Time from randomization to the first skeletal-related event.

Time frame
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.

Time frame
At 6 months and 12 months after randomization

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Tongji Hospital

Lead sponsor

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: