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

NCT03520231 | Completed Phase 2 DMC

• 1 other identifier: DENIM
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Urothelial Carcinoma; Kidney Cancer; Ureter Cancer; Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• 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%.

  Baseline to Week 10

Secondary Outcomes (18)

• Number of patients with a change in sCTx

  Baseline to Week 10

• Mean percentage change in serum bone-specific alkaline phosphatase (bALP) in the investigational arm

  Baseline to Week 10

• Mean percentage change in urinary N-telopeptide (uNTx) levels in the investigational arm

  Baseline to Week 10

• Mean percentage change in sCTx levels in the investigational arm

  Baseline to End of Chemotherapy (Week 20)

• Mean percentage change in bALP levels in the investigational arm

  Baseline to End of Chemotherapy (Week 20)

Study Arms (2)

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.

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.

Other: Denosumab Placebo; Drug: Gemcitabine; Drug: Carboplatin; Drug: Cisplatin; Dietary Supplement: Calcium; Dietary Supplement: Vitamin D

Interventions

Denosumab DRUG

RANK Ligand Inhibitor

Also known as: XGEVA

Denosumab and Standard Chemotherapy

Denosumab Placebo OTHER

Placebo

Denosumab Placebo and Standard Chemotherapy

Gemcitabine DRUG

Antineoplastic Agent

Denosumab Placebo and Standard Chemotherapy; Denosumab and Standard Chemotherapy

Carboplatin DRUG

Antineoplastic Agent

Denosumab Placebo and Standard Chemotherapy; Denosumab and Standard Chemotherapy

Cisplatin DRUG

Antineoplastic Agent

Denosumab Placebo and Standard Chemotherapy; Denosumab and Standard Chemotherapy

Calcium DIETARY_SUPPLEMENT

Calcium Supplement

Denosumab Placebo and Standard Chemotherapy; Denosumab and Standard Chemotherapy

Vitamin D DIETARY_SUPPLEMENT

Vitamin D Supplement

Denosumab Placebo and Standard Chemotherapy; Denosumab and Standard Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Amgen: collaborator

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Kidney Neoplasms; Ureteral Neoplasms; Urinary Bladder Neoplasms

Interventions

Denosumab; Gemcitabine; Carboplatin; Cisplatin; Calcium; Vitamin D

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Ureteral Diseases; Urinary Bladder Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Alkaline Earth; Elements; Metals; Blood Coagulation Factors; Biological Factors; Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Srikala Sridhar, M.D.

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2018
• First Posted: May 9, 2018
• Study Start: September 4, 2018
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: November 23, 2021

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)