Risk Factors for Skeletal Related Events in Breast Cancer Patients Receiving Bisphosphonates for Bone Metastases

Breast Cancer Clinical Trial

— PROVISTII  

Official title:

Prospective Identification of Risk Factors for Skeletal Related Events in Breast Cancer Patients Receiving Bisphosphonates for Bone Metastases

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01144481
• Other study ID #: PROVISTII
• Status: Completed
• Phase: N/A
• First received: June 11, 2010
• Last updated: January 6, 2015
• Start date: February 2009
• Est. completion date: April 2013

Study information

• Verified date: January 2015
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Observational

Clinical Trial Summary

Bone is the most common site of distant breast cancer recurrence, and 65-75% of women with advanced breast cancer will develop bone metastases during the course of their disease. The most pressing problem in management of bony metastases today, is the inability to reliably identify patients at high risk for skeletal related events (SREs) (such as bone fractures, surgery/radiotherapy for pain or prevention of fractures, high calcium levels, and spinal cord compression) despite the standard use of bone medication (bisphosphonates). Using the latest innovations both in imaging and blood tests, this novel pilot project will develop a risk model for predicting bone metastases, which will be able to identify patients who would most benefit from novel treatments, such as the multikinase inhibitor Zactima and the Src inhibitor, AZD0530. Given that approximately 1/3 of patients with metastatic breast cancer and bony disease will sustain an SRE despite use of a bisphosphonate, there is an urgent unmet need in this large population to introduce effective bone protective agents.

Description:

Bone is the most common site of distant breast cancer recurrence, and 65-75% of women with advanced breast cancer will develop bone metastases during the course of their disease. Bone metastases can significantly adversely impact on quality of life by causing pain and skeletal related events (SREs) such as pathological fractures, surgery/radiotherapy for pain/prevention of fractures, hypercalcemia, and spinal cord compression. These complications of bone metastases may necessitate multiple medical, surgical, and radiation interventions. Indeed, prior to the widespread use of bisphosphonates, over two thirds (2/3) of women with bone metastases developed at least one SRE. Despite prolonged bisphosphonate use, many patients will continue to have progression of their bone metastases and develop SREs. The most pressing problem in management of bony metastases today, is the inability to reliably identify patients at high risk for SREs despite standard bisphosphonate use.

Using a prospective, observational trial design, we will develop a prognostic model with baseline serum C-telopeptide (sCTx) as the predictor variable and SREs as the outcome variable. 60 breast cancer patients with metastases to any site will be approached for participation in this prospective single centered study. Baseline characteristics (and potential risk factors) will be recorded upon study enrollment, including clinical factors (prior fragility fracture, use of corticosteroids, age), bone mineral density, performance status, measures of quality of life and pain. Novel markers such as sCTx and bone specific alkaline phosphatase (bALP) will also be assessed. The WHO fracture risk assessment tool (http://www.shef.ac.uk) will be used to estimate baseline fracture risk according to osteoporosis guidelines and a calcium intake diet history will be taken. In addition, assessment of vertebral fractures will take place using two novel techniques, bone densitometric vertebral fracture assessment (VFA) and high resolution quantitative CT (HR-pQCT). Bone mineral density along with VFA will be performed at baseline and at one year of treatment.

Patients will be assessed every twelve weeks for twenty-four months with regards to:

symptoms related to SREs, ECOG status, pain (using the BPI, a 7-point scale of analgesic use), and quality of life (using the FACT-BP, and FACT-BTSQ). In addition to being measured at baseline, sCTx and bALP will be measured every twelve weeks for twenty-four months. Calcium and 25-hydroxy vitamin D will be measured annually as part of regular clinical practice, and a CT scan of the thorax and abdomen as well as a bone scan will be preformed at least once yearly as part of regular clinical practice for patients with metastatic breast cancer.

Using the latest innovations both in imaging and medical biomarkers, this novel pilot project will develop a prospective risk model for predicting bone metastases, which will be able to identify patients who would most benefit from novel treatments, such as the multikinase inhibitor Zactima and the Src inhibitor, AZD0530.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• patients with metastatic breast cancer treated at Princess Margaret Hospital

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Bone Marrow Diseases
• Bone Metastases
• Bone Neoplasms
• Breast Cancer
• Breast Neoplasms
• Neoplasm Metastasis

Locations

Country	Name	City	State
Canada	University Health Network	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
University Health Network, Toronto	AstraZeneca

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Skeletal related event	Primary outcome is any SRE such as pathological fractures, surgery/radiotherapy for pain/prevention of fractures, hypercalcemia, and spinal cord compression.	0 to 24 months	No