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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01144481
First received: June 11, 2010
Last updated: July 5, 2013
Last verified: July 2013
  Purpose

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.


Condition
Bone Metastases
Breast Cancer

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Prospective Identification of Risk Factors for Skeletal Related Events in Breast Cancer Patients Receiving Bisphosphonates for Bone Metastases

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Skeletal related event [ Time Frame: 0 to 24 months ] [ Designated as safety issue: No ]
    Primary outcome is any SRE such as pathological fractures, surgery/radiotherapy for pain/prevention of fractures, hypercalcemia, and spinal cord compression.


Biospecimen Retention:   Samples Without DNA

serum and urine


Estimated Enrollment: 60
Study Start Date: February 2009
Estimated Study Completion Date: January 2015
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
breast cancer with metastasis
female breast cancer patients with metastases to any site

Detailed 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.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

female breast cancer patients with metastases to any site

Criteria

Inclusion Criteria:

  • patients with metastatic breast cancer treated at Princess Margaret Hospital
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01144481

Locations
Canada, Ontario
University Health Network
Toronto, Ontario, Canada, M5G 2C4
Sponsors and Collaborators
University Health Network, Toronto
AstraZeneca
Investigators
Principal Investigator: Angela MW Cheung, MD, PhD University Health Network, Toronto
  More Information

No publications provided

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01144481     History of Changes
Other Study ID Numbers: PROVISTII
Study First Received: June 11, 2010
Last Updated: July 5, 2013
Health Authority: Canada: Health Canada

Keywords provided by University Health Network, Toronto:
bone metastasis
breast cancer
skeletal related event
HR-pQCT
VFA

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Bone Neoplasms
Bone Marrow Diseases
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Bone Diseases
Musculoskeletal Diseases
Hematologic Diseases
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 31, 2014