Brief Title
Study Comparing Denosumab With Standard Treatment in Urothelial Cancer Patients With Bone Metastases
Official Title
A Multicenter 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
Brief 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.
Detailed Description
This is a multicenter, 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.
Study Phase
Phase 2
Study Type
Interventional
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
Condition
Urothelial Carcinoma
Intervention
Denosumab
Study Arms / Comparison Groups
Denosumab and Standard Chemotherapy
Description: Denosumab, given subcutaneously at a dose of 120 mg, every 4 weeks. Gemcitabine, given intravenously at standard doses, on Days 1 and 8 of every 21 day cycle, for 3-4 cycles. Carboplatin, given intravenously at standard doses, on Day 1 of every 21 day cycle, for 3-4 cycles. OR Cisplatin, given intravenously at standard doses, on Day 1 of every 21 day cycle, for 3-4 cycles. Calcium, orally at a dose of 1000 mg, once daily. Vitamin D, orally at a dose of 400 IU, once daily.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
6
Start Date
September 4, 2018
Completion Date
December 1, 2020
Primary Completion Date
December 1, 2020
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed urothelial carcinoma (kidney, ureter,
bladder) with metastatic disease involving the bones, not amenable to curative
treatment
- Mixed histologies permitted as long as urothelial histology is the major component
Presence of one or more bone metastases
- No prior systemic chemotherapy for metastatic disease (immunotherapy permitted)
- Starting first line chemotherapy for metastatic urothelial cancer with gemcitabine and
cisplatin or gemcitabine and carboplatin and planned to receive 4-6 cycles
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Adequate renal function
- Acceptable serum calcium or albumin-adjusted serum calcium
- Adequate hepatic function
- Patients all require oral examination and appropriate preventative dentistry prior to
starting treatment
- Expected life expectancy of at least 3 months
Exclusion Criteria:
- Prior chemotherapy for metastatic disease
- Current or prior IV bisphosphonate or denosumab administration
- Current or prior oral bisphosphonate administration to treat bone metastases
- Unacceptable renal function
- Abnormal bone metabolism (Paget's disease)
- Untreated or symptomatic brain metastases
- Patients with a history of other malignancies, with exceptions
- Significant dental/oral disease
- Administration of other prior anticancer therapies within 2 weeks of randomization
- Patient is pregnant or breast feeding, or planning to become pregnant within 7 months
after the end of treatment
- Female of child bearing potential is not willing to use, in combination with her
partner, highly effective contraception during treatment and for 7 months after the
end of treatment
- Known sensitivity to any of the products to be administered during the study
- History of any other clinically significant disorder, condition or disease that in the
opinion of the investigator excludes the patient
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Srikala Sridhar, M.D., ,
Location Countries
Canada
Location Countries
Canada
Administrative Informations
NCT ID
NCT03520231
Organization ID
DENIM
Responsible Party
Sponsor
Study Sponsor
University Health Network, Toronto
Collaborators
Amgen
Study Sponsor
Srikala Sridhar, M.D., Principal Investigator, Princess Margaret Cancer Centre
Verification Date
September 2020