Urothelial CarcinomaPhase 2NCT03520231
Study Comparing Denosumab With Standard Treatment in Urothelial Cancer Patients With Bone Metastases
A Phase 2 study testing Denosumab, Gemcitabine and Carboplatin in people with Urothelial Carcinoma and Kidney Cancer, run by University Health Network, Toronto at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urothelial Carcinoma, Kidney Cancer, Ureter Cancer
- What is being tested?
- Denosumab, Gemcitabine and Carboplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 1 siteCanada
- Study dates
- 4 Sep 2018to 1 Dec 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Urothelial Carcinoma, Kidney Cancer, Ureter Cancer, Bladder Cancer
- Being tested
- Denosumab, Denosumab Placebo, Gemcitabine, Carboplatin, Cisplatin
- Medical subject headings
- Carcinoma, Transitional Cell, Kidney Neoplasms, Ureteral Neoplasms, Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DenosumabDrug
Also called XGEVA
RANK Ligand Inhibitor
Denosumab PlaceboOther
Placebo
GemcitabineDrug
Antineoplastic Agent
CarboplatinDrug
Antineoplastic Agent
CisplatinDrug
Antineoplastic Agent
CalciumDietary supplement
Calcium Supplement
Vitamin DDietary supplement
Vitamin D Supplement
| Study group | Role | What they receive |
|---|---|---|
| Denosumab and Standard Chemotherapy | Experimental | 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. Receives: Drug: Denosumab; Drug: Gemcitabine; Drug: Carboplatin; Drug: Cisplatin; Dietary Supplement: Calcium; Dietary Supplement: Vitamin D |
| Denosumab Placebo and Standard Chemotherapy | Placebo comparator | Denosumab placebo, given subcutaneously, 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. Receives: Other: Denosumab Placebo; Drug: Gemcitabine; Drug: Carboplatin; Drug: Cisplatin; Dietary Supplement: Calcium; Dietary Supplement: Vitamin D |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in mean percentage change in serum c-telopeptide (sCTX) between the two arms (investigational drug arm and placebo arm).
Mean percentage change should be greater than or equal to 30%.
Measured: Baseline to Week 10
Secondary outcomes (18)
Number of patients with a change in sCTx
To determine the proportion of patients with a change in sCTx of >30% from baseline at week 1 to week 10
Measured: Baseline to Week 10
Mean percentage change in serum bone-specific alkaline phosphatase (bALP) in the investigational arm
Measured: Baseline to Week 10
Mean percentage change in urinary N-telopeptide (uNTx) levels in the investigational arm
Measured: Baseline to Week 10
Mean percentage change in sCTx levels in the investigational arm
Measured: Baseline to End of Chemotherapy (Week 20)
Mean percentage change in bALP levels in the investigational arm
Measured: Baseline to End of Chemotherapy (Week 20)
Mean percentage change in uNTx levels in the investigational arm
Measured: Baseline to End of Chemotherapy (Week 20)
Mean percentage change in serum bone-specific alkaline phosphatase (bALP) in the placebo arm.
Measured: Baseline to Week 10
Mean percentage change in urinary N-telopeptide (uNTx) levels in the placebo arm.
Measured: Baseline to Week 10
Mean percentage change in sCTx levels in the levels in the placebo arm.
Measured: Baseline to End of Chemotherapy (Week 20)
Mean percentage change in bALP levels in the levels in the placebo arm.
Measured: Baseline to End of Chemotherapy (Week 20)
Mean percentage change in uNTx levels in the levels in the placebo arm.
Measured: Baseline to End of Chemotherapy (Week 20)
Time to first on study symptomatic skeletal related events
To determine and compare the time to first on study symptomatic skeletal related events (SSE); (fracture, surgery, radiation to bone, or spinal cord compression) between each arm of the study
Measured: 2 years
Progression free survival rate
To determine progression free survival (PFS) in each arm at 1 year (with appropriate censoring) after last dose of chemotherapy
Measured: 1 year
Progression free survival rate
To determine progression free survival (PFS) in each arm at 18 months (with appropriate censoring) after last dose of chemotherapy
Measured: 18 months
Overall survival rate
To determine overall survival (OS) rate at 1 year (with appropriate censoring) after last dose of chemotherapy
Measured: 1 year
Overall survival rate
To determine overall survival (OS) rate at 18 months (with appropriate censoring) after last dose of chemotherapy
Measured: 18 months
Number of participants with side effects in the investigational drug arm
To evaluate safety and tolerability
Measured: 2 years
Number of participants with side effects in the placebo arm
To evaluate safety and tolerability
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2018
- Study start4 Sep 2018
- Primary completion1 Dec 2020
- Study completion1 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Sponsor
- Investigators
- Srikala Sridhar, M.D., Principal investigator, Princess Margaret Cancer Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03520231
- Sponsor's protocol ID
- DENIM
- Status last verified
- Sep 2020
- First submitted
- 27 Apr 2018
- Last updated
- 23 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03520231
- Acronym / sponsor ID
- DENIM
- Conditions
- Urothelial Carcinoma, Kidney Cancer, Ureter Cancer, Bladder Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- 4 Sep 2018 (actual)
- Primary completion
- 1 Dec 2020 (actual)
- Study completion
- 1 Dec 2020 (actual)
- First posted
- 9 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Denosumab and Standard Chemotherapy | Experimental | Drug: Denosumab, Drug: Gemcitabine, Drug: Carboplatin, Drug: Cisplatin, Dietary Supplement: Calcium, Dietary Supplement: Vitamin DDenosumab, 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. |
| Denosumab Placebo and Standard Chemotherapy | Placebo comparator | Other: Denosumab Placebo, Drug: Gemcitabine, Drug: Carboplatin, Drug: Cisplatin, Dietary Supplement: Calcium, Dietary Supplement: Vitamin DDenosumab placebo, given subcutaneously, 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (13 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DenosumabAlso: XGEVARANK Ligand Inhibitor | Drug | Denosumab and Standard Chemotherapy |
| Denosumab PlaceboPlacebo | Other | Denosumab Placebo and Standard Chemotherapy |
| GemcitabineAntineoplastic Agent | Drug | Denosumab Placebo and Standard Chemotherapy, Denosumab and Standard Chemotherapy |
| CarboplatinAntineoplastic Agent | Drug | Denosumab Placebo and Standard Chemotherapy, Denosumab and Standard Chemotherapy |
| CisplatinAntineoplastic Agent | Drug | Denosumab Placebo and Standard Chemotherapy, Denosumab and Standard Chemotherapy |
| CalciumCalcium Supplement | Dietary supplement | Denosumab Placebo and Standard Chemotherapy, Denosumab and Standard Chemotherapy |
| Vitamin DVitamin D Supplement | Dietary supplement | Denosumab Placebo and Standard Chemotherapy, Denosumab and Standard Chemotherapy |
Primary outcome
Difference in mean percentage change in serum c-telopeptide (sCTX) between the two arms (investigational drug arm and placebo arm).
Time frame: Baseline to Week 10
Mean percentage change should be greater than or equal to 30%.
18 secondary outcomes
Number of patients with a change in sCTx
Time frame: Baseline to Week 10
Mean percentage change in serum bone-specific alkaline phosphatase (bALP) in the investigational arm
Time frame: Baseline to Week 10
Mean percentage change in urinary N-telopeptide (uNTx) levels in the investigational arm
Time frame: Baseline to Week 10
Mean percentage change in sCTx levels in the investigational arm
Time frame: Baseline to End of Chemotherapy (Week 20)
Mean percentage change in bALP levels in the investigational arm
Time frame: Baseline to End of Chemotherapy (Week 20)
Mean percentage change in uNTx levels in the investigational arm
Time frame: Baseline to End of Chemotherapy (Week 20)
Mean percentage change in serum bone-specific alkaline phosphatase (bALP) in the placebo arm.
Time frame: Baseline to Week 10
Mean percentage change in urinary N-telopeptide (uNTx) levels in the placebo arm.
Time frame: Baseline to Week 10
Mean percentage change in sCTx levels in the levels in the placebo arm.
Time frame: Baseline to End of Chemotherapy (Week 20)
Mean percentage change in bALP levels in the levels in the placebo arm.
Time frame: Baseline to End of Chemotherapy (Week 20)
Mean percentage change in uNTx levels in the levels in the placebo arm.
Time frame: Baseline to End of Chemotherapy (Week 20)
Time to first on study symptomatic skeletal related events
Time frame: 2 years
Progression free survival rate
Time frame: 1 year
Progression free survival rate
Time frame: 18 months
Overall survival rate
Time frame: 1 year
Overall survival rate
Time frame: 18 months
Number of participants with side effects in the investigational drug arm
Time frame: 2 years
Number of participants with side effects in the placebo arm
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Srikala Sridhar, M.D. principal investigator
Princess Margaret Cancer Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Denosumab, Gemcitabine and Carboplatin in people with Urothelial Carcinoma and Kidney Cancer, run by University Health Network, Toronto at 1 site in Canada.
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 10 inclusion and 13 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: finished, as of the sponsor's last update on 23 Nov 2021. 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 Canada. 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. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in mean percentage change in serum c-telopeptide (sCTX) between the two arms (investigational drug arm and placebo arm). (time frame: Baseline to Week 10). 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 23 Nov 2021.