Study Comparing Denosumab With Standard Treatment in Urothelial Cancer Patients With Bone Metastases

Official Title

A Multicentre Randomized Double Blind Study Examining the Efficacy and Safety of Denosumab in Combination With First Line Platinum-based Chemotherapy for Patients With Bone Metastasis Secondary to Metastatic Urothelial Cancer

Summary:

This is a phase 2 study of the drug denosumab for the management bone metastases from urothelial cancer. The purpose of this study is to find out how effective denosumab is in the management of bone metastases from urothelial cancer. This will be done by comparing denosumab with standard treatment, compared to placebo and standard treatment. Denosumab is a monoclonal antibody that binds to a protein called Receptor Activator of Nuclear Factor κB (RANK). RANK works by telling certain cells called osteoclasts to break down bone tissue. The binding of denosumab to RANK stops it from telling osteoclasts to break down bone tissue which may help with symptoms related bone metastases from urothelial cancer.

Trial Description

Primary Outcome:

  • Difference in mean percentage change in serum c-telopeptide (sCTX) between the two arms (investigational drug arm and placebo arm).
Secondary Outcome:
  • Number of patients with a change in sCTx
  • Mean percentage change in serum bone-specific alkaline phosphatase (bALP) in the investigational arm
  • Mean percentage change in urinary N-telopeptide (uNTx) levels in the investigational arm
  • Mean percentage change in sCTx levels in the investigational arm
  • Mean percentage change in bALP levels in the investigational arm
  • Mean percentage change in uNTx levels in the investigational arm
  • Mean percentage change in serum bone-specific alkaline phosphatase (bALP) in the placebo arm.
  • Mean percentage change in urinary N-telopeptide (uNTx) levels in the placebo arm.
  • Mean percentage change in sCTx levels in the levels in the placebo arm.
  • Mean percentage change in bALP levels in the levels in the placebo arm.
  • Mean percentage change in uNTx levels in the levels in the placebo arm.
  • Time to first on study symptomatic skeletal related events
  • Progression free survival rate
  • Progression free survival rate
  • Overall survival rate
  • Overall survival rate
  • Number of participants with side effects in the investigational drug arm
  • Number of participants with side effects in the placebo arm
This is a multicentre, randomized, double blind, Phase II study. Participants eligible for this study have metastatic urothelial cancer and bone metastases and are planned to receive 4-6 cycles of a standard of care platinum-doublet regimen. In a double blind manner, 50 participants will be randomized in a 1:1 ratio to receive denosumab 120 mg or matching placebo subcutaneously every 4 weeks with their first dose coinciding with the first cycle of chemotherapy. Patients will continue on denosumab/placebo even after all planned chemotherapy cycles have been delivered and until the end of the study at 18 months after the last dose of chemotherapy. Patients with symptomatic progression in the bone may be unblinded and crossed over to denosumab (if on placebo). All participants will be provided with 1000 mg of calcium and 400 IU of vitamin D to be taken daily. Participants who discontinue the investigational product early will be followed for disease status and survival.

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society