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Study to Evaluate the Safety and Effects AZD0530 on Prostate and Breast Cancer Subjects With Metastatic Bone Disease

Primary Purpose

Breast Cancer, Prostate Cancer, Bone Neoplasms

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AZD0530
Zoledronic Acid
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring breast cancer, prostate cancer, metastatic bone disease, Subjects with breast cancer or prostate cancer with metastatic bone disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subjects 18 years or older with Prostate Cancer or Breast Cancer with Metastatic Bone Disease Have evidence of recurrence or disease progression
  • At least one radiographically confirmed metastatic bone lesion
  • No change of cancer therapy for at least 8 weeks before randomization

Exclusion Criteria:

  • Have had any prior exposure to bisphosphonate
  • Have had hip fractures or bilateral hip prothesis fracture of any kind or surgery to bone within the past 12 months
  • Inadequate renal function or low haemoglobin
  • Inadequate liver function as demonstrated by serum bilirubin ≥2 times the upper limits of reference range (ULRR) or by alanine aminotransferase (ALT), aspartate aminotransferase(AST) or ALP ≥2.5 times the ULRR (≥5 times the ULRR in the presence of liver metastases). If bone metastases are present and liver function is otherwise considered adequate by the investigator then elevated ALP will not exclude the patient.

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

AZD0530 175 mg

Zoledronic Acid 4 mg

Arm Description

AZD0530 (saracatinib) 175 mg once daily

Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

Outcomes

Primary Outcome Measures

Percentage Change From Baseline in Serum Beta C-terminal Cross-linking Telopeptide of Type I Collagen (betaCTX) at Week 4
Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean.

Secondary Outcome Measures

Percentage Change From Baseline in Serum Bone-specific Alkaline Phosphatase (bALP) at Week 4
Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean.
Percentage Change From Baseline in Serum Cross-linked C-terminal Telopeptide of Type I Collagen (ICTP) at Week 4
Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean.
Percentage Change From Baseline in Serum N-terminal Propeptide of Type I Procollagen (PINP) at Week 4
Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean.
Percentage Change From Baseline in Serum Tartrate-resistant Acid Phosphatase 5b (TRAP5b) at Week 4
Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean.
Percentage Change From Baseline in Urine N-terminal Cross-linking Telopeptide of Type I Collagen Normalised to Creatinine (NTx/Cr) at Week 4
Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean.
Percentage Change From Baseline in Urine Alpha-alpha C-terminal Cross-linking Telopeptide of Type I Collagen Normalised to Creatinine (aaCTx/Cr) at Week 4
Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean.
Saracatinib: Area Under the Curve at Steady State (AUCss)
Previous studies have shown that saracatinib reduces osteoclast function and bone resorption. Bone turnover, the combined result of bone formation and bone resorption, can be assessed in real time by measuring specific markers of bone turnover in serum and in urine. These markers were assessed in a study of patients with metastatic bone disease treated with saracatinib. Specific assays are available to quantitate these markers in serum and urine. In this study the effects of saracatinib on bone turnover were compared with the effects of zoledronic acid, a marketed drug known to inhibit bone resorption in cancer patients with bone metastatses.
Saracatinib: Plasma Clearance at Steady State (CLss/F)
Saracatinib: Maximum Plasma Concentration at Steady State (Css,Max)
Saracatinib: Minimum Plasma Concentration at Steady State (Css,Min)
Saracatinib: Time to Cssmax (Tmax)
N-desmethyl Metabolite of Saracatinib: Area Under the Curve at Steady State (AUCss)
N-desmethyl Metabolite of Saracatinib: Maximum Plasma Concentration at Steady State (Css,Max)
N-desmethyl Metabolite of Saracatinib: Minimum Plasma Concentration at Steady State (Css,Min)
N-desmethyl Metabolite of Saracatinib: AUCss Metabolite to Parent Ratio
N-desmethyl Metabolite of Saracatinib: Time to Cssmax (Tmax)

Full Information

First Posted
November 13, 2007
Last Updated
May 23, 2013
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT00558272
Brief Title
Study to Evaluate the Safety and Effects AZD0530 on Prostate and Breast Cancer Subjects With Metastatic Bone Disease
Official Title
A Phase II, Randomised, Open-Label, Pilot Study to Evaluate the Safety and Effects on Bone Resorption of AZD0530 in Patients With Prostate Cancer or Breast Cancer With Metastatic Bone Disease.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2013
Overall Recruitment Status
Completed
Study Start Date
February 2008 (undefined)
Primary Completion Date
January 2010 (Actual)
Study Completion Date
August 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine the effect of AZD0530 on subjects with breast cancer or prostate cancer with metastatic bone disease in comparison to zoledronic acid.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Prostate Cancer, Bone Neoplasms
Keywords
breast cancer, prostate cancer, metastatic bone disease, Subjects with breast cancer or prostate cancer with metastatic bone disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
139 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AZD0530 175 mg
Arm Type
Experimental
Arm Description
AZD0530 (saracatinib) 175 mg once daily
Arm Title
Zoledronic Acid 4 mg
Arm Type
Experimental
Arm Description
Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period
Intervention Type
Drug
Intervention Name(s)
AZD0530
Other Intervention Name(s)
Saracatinib
Intervention Description
Daily oral dose
Intervention Type
Drug
Intervention Name(s)
Zoledronic Acid
Other Intervention Name(s)
Zometa
Primary Outcome Measure Information:
Title
Percentage Change From Baseline in Serum Beta C-terminal Cross-linking Telopeptide of Type I Collagen (betaCTX) at Week 4
Description
Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean.
Time Frame
Baseline to Week 4
Secondary Outcome Measure Information:
Title
Percentage Change From Baseline in Serum Bone-specific Alkaline Phosphatase (bALP) at Week 4
Description
Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean.
Time Frame
Baseline to Week 4
Title
Percentage Change From Baseline in Serum Cross-linked C-terminal Telopeptide of Type I Collagen (ICTP) at Week 4
Description
Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean.
Time Frame
Baseline to Week 4
Title
Percentage Change From Baseline in Serum N-terminal Propeptide of Type I Procollagen (PINP) at Week 4
Description
Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean.
Time Frame
Baseline to Week 4
Title
Percentage Change From Baseline in Serum Tartrate-resistant Acid Phosphatase 5b (TRAP5b) at Week 4
Description
Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean.
Time Frame
Baseline to Week 4
Title
Percentage Change From Baseline in Urine N-terminal Cross-linking Telopeptide of Type I Collagen Normalised to Creatinine (NTx/Cr) at Week 4
Description
Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean.
Time Frame
Baseline to Week 4
Title
Percentage Change From Baseline in Urine Alpha-alpha C-terminal Cross-linking Telopeptide of Type I Collagen Normalised to Creatinine (aaCTx/Cr) at Week 4
Description
Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean.
Time Frame
Baseline to Week 4
Title
Saracatinib: Area Under the Curve at Steady State (AUCss)
Description
Previous studies have shown that saracatinib reduces osteoclast function and bone resorption. Bone turnover, the combined result of bone formation and bone resorption, can be assessed in real time by measuring specific markers of bone turnover in serum and in urine. These markers were assessed in a study of patients with metastatic bone disease treated with saracatinib. Specific assays are available to quantitate these markers in serum and urine. In this study the effects of saracatinib on bone turnover were compared with the effects of zoledronic acid, a marketed drug known to inhibit bone resorption in cancer patients with bone metastatses.
Time Frame
Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
Title
Saracatinib: Plasma Clearance at Steady State (CLss/F)
Time Frame
Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
Title
Saracatinib: Maximum Plasma Concentration at Steady State (Css,Max)
Time Frame
Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
Title
Saracatinib: Minimum Plasma Concentration at Steady State (Css,Min)
Time Frame
Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
Title
Saracatinib: Time to Cssmax (Tmax)
Time Frame
Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
Title
N-desmethyl Metabolite of Saracatinib: Area Under the Curve at Steady State (AUCss)
Time Frame
Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
Title
N-desmethyl Metabolite of Saracatinib: Maximum Plasma Concentration at Steady State (Css,Max)
Time Frame
Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
Title
N-desmethyl Metabolite of Saracatinib: Minimum Plasma Concentration at Steady State (Css,Min)
Time Frame
Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
Title
N-desmethyl Metabolite of Saracatinib: AUCss Metabolite to Parent Ratio
Time Frame
Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
Title
N-desmethyl Metabolite of Saracatinib: Time to Cssmax (Tmax)
Time Frame
Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects 18 years or older with Prostate Cancer or Breast Cancer with Metastatic Bone Disease Have evidence of recurrence or disease progression At least one radiographically confirmed metastatic bone lesion No change of cancer therapy for at least 8 weeks before randomization Exclusion Criteria: Have had any prior exposure to bisphosphonate Have had hip fractures or bilateral hip prothesis fracture of any kind or surgery to bone within the past 12 months Inadequate renal function or low haemoglobin Inadequate liver function as demonstrated by serum bilirubin ≥2 times the upper limits of reference range (ULRR) or by alanine aminotransferase (ALT), aspartate aminotransferase(AST) or ALP ≥2.5 times the ULRR (≥5 times the ULRR in the presence of liver metastases). If bone metastases are present and liver function is otherwise considered adequate by the investigator then elevated ALP will not exclude the patient.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Finkelman, DDS, PhD
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Meabe Aklilu, MD
Organizational Affiliation
Wake Forest University Health Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Pleasant Hill
State/Province
California
Country
United States
Facility Name
Research Site
City
Sacramento
State/Province
California
Country
United States
Facility Name
Research Site
City
Middlebury
State/Province
Connecticut
Country
United States
Facility Name
Research Site
City
Aventura
State/Province
Florida
Country
United States
Facility Name
Research Site
City
Baltimore
State/Province
Maryland
Country
United States
Facility Name
Research Site
City
Ann Arbor
State/Province
Michigan
Country
United States
Facility Name
Research Site
City
Poughkeepsie
State/Province
New York
Country
United States
Facility Name
Research Site
City
Winston-salem
State/Province
North Carolina
Country
United States
Facility Name
Research Site
City
Hershey
State/Province
Pennsylvania
Country
United States
Facility Name
Research Site
City
Edmonton
State/Province
Alberta
Country
Canada
Facility Name
Research Site
City
Vancouver
State/Province
British Columbia
Country
Canada
Facility Name
Research Site
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
Research Site
City
Montreal
State/Province
Quebec
Country
Canada
Facility Name
Research Site
City
Quebec
Country
Canada
Facility Name
Research Site
City
Arhus N
Country
Denmark
Facility Name
Research Site
City
Frederica
Country
Denmark
Facility Name
Research Site
City
Herlev
Country
Denmark
Facility Name
Research Site
City
Holstebro
Country
Denmark
Facility Name
Research Site
City
Kristiansand
Country
Norway
Facility Name
Research Site
City
Oslo
Country
Norway
Facility Name
Research Site
City
Lisboa
Country
Portugal
Facility Name
Research Site
City
Barcelona
State/Province
Cataluna
Country
Spain
Facility Name
Research Site
City
Lerida
State/Province
Cataluna
Country
Spain
Facility Name
Research Site
City
Valencia
State/Province
Comunidad Valenciana
Country
Spain
Facility Name
Research Site
City
Uppsala
Country
Sweden
Facility Name
Research Site
City
Cardiff
Country
United Kingdom
Facility Name
Research Site
City
Glasgow
Country
United Kingdom
Facility Name
Research Site
City
Manchester
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

Study to Evaluate the Safety and Effects AZD0530 on Prostate and Breast Cancer Subjects With Metastatic Bone Disease

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