Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03520231
Recruitment Status : Recruiting
First Posted : May 9, 2018
Last Update Posted : February 4, 2019
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
University Health Network, Toronto

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.


Condition or disease Intervention/treatment Phase
Urothelial Carcinoma Kidney Cancer Ureter Cancer Bladder Cancer Drug: Denosumab Other: Denosumab Placebo Drug: Gemcitabine Drug: Carboplatin Drug: Cisplatin Dietary Supplement: Calcium Dietary Supplement: Vitamin D Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : September 4, 2018
Estimated Primary Completion Date : December 1, 2019
Estimated Study Completion Date : June 1, 2020


Arm Intervention/treatment
Experimental: Denosumab and Standard Chemotherapy

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.

Drug: Denosumab
RANK Ligand Inhibitor
Other Name: XGEVA

Drug: Gemcitabine
Antineoplastic Agent

Drug: Carboplatin
Antineoplastic Agent

Drug: Cisplatin
Antineoplastic Agent

Dietary Supplement: Calcium
Calcium Supplement

Dietary Supplement: Vitamin D
Vitamin D Supplement

Placebo Comparator: Denosumab Placebo and Standard Chemotherapy

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.

Other: Denosumab Placebo
Placebo

Drug: Gemcitabine
Antineoplastic Agent

Drug: Carboplatin
Antineoplastic Agent

Drug: Cisplatin
Antineoplastic Agent

Dietary Supplement: Calcium
Calcium Supplement

Dietary Supplement: Vitamin D
Vitamin D Supplement




Primary Outcome Measures :
  1. 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%.


Secondary Outcome Measures :
  1. Number of patients with a change in sCTx [ Time Frame: Baseline to Week 10 ]
  2. Mean percentage change in serum bone-specific alkaline phosphatase (bALP) in the investigational arm [ Time Frame: Baseline to Week 10 ]
  3. Mean percentage change in urinary N-telopeptide (uNTx) levels in the investigational arm [ Time Frame: Baseline to Week 10 ]
  4. Mean percentage change in sCTx levels in the investigational arm [ Time Frame: Baseline to End of Chemotherapy (Week 20) ]
  5. Mean percentage change in bALP levels in the investigational arm [ Time Frame: Baseline to End of Chemotherapy (Week 20) ]
  6. Mean percentage change in uNTx levels in the investigational arm [ Time Frame: Baseline to End of Chemotherapy (Week 20) ]
  7. Mean percentage change in serum bone-specific alkaline phosphatase (bALP) in the placebo arm. [ Time Frame: Baseline to Week 10 ]
  8. Mean percentage change in urinary N-telopeptide (uNTx) levels in the placebo arm. [ Time Frame: Baseline to Week 10 ]
  9. Mean percentage change in sCTx levels in the levels in the placebo arm. [ Time Frame: Baseline to End of Chemotherapy (Week 20) ]
  10. Mean percentage change in bALP levels in the levels in the placebo arm. [ Time Frame: Baseline to End of Chemotherapy (Week 20) ]
  11. Mean percentage change in uNTx levels in the levels in the placebo arm. [ Time Frame: Baseline to End of Chemotherapy (Week 20) ]
  12. Time to first on study symptomatic skeletal related events [ Time Frame: 2 years ]
  13. Progression free survival rate [ Time Frame: 1 year ]
  14. Progression free survival rate [ Time Frame: 18 months ]
  15. Overall survival rate [ Time Frame: 1 year ]
  16. Overall survival rate [ Time Frame: 18 months ]
  17. Number of participants with side effects in the investigational drug arm [ Time Frame: 2 years ]
  18. Number of participants with side effects in the placebo arm [ Time Frame: 2 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03520231


Contacts
Layout table for location contacts
Contact: Srikala Sridhar, M.D. 416-946-4501 ext 2662 srikala.sridhar@uhn.ca

Locations
Layout table for location information
Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Srikala Sridhar, M.D.    416-946-4501 ext 2662    srikala.sridhar@uhn.ca   
Principal Investigator: Srikala Sridhar, M.D.         
Sponsors and Collaborators
University Health Network, Toronto
Amgen
Investigators
Layout table for investigator information
Principal Investigator: Srikala Sridhar, M.D. Princess Margaret Cancer Centre

Layout table for additonal information
Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT03520231     History of Changes
Other Study ID Numbers: DENIM
First Posted: May 9, 2018    Key Record Dates
Last Update Posted: February 4, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Urinary Bladder Neoplasms
Kidney Neoplasms
Carcinoma, Renal Cell
Carcinoma, Transitional Cell
Ureteral Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Kidney Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Ureteral Diseases
Vitamin D
Ergocalciferols
Calcium, Dietary
Denosumab
Vitamins
Gemcitabine
Cisplatin
Carboplatin
Antineoplastic Agents
Calcium
Micronutrients
Nutrients
Growth Substances