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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00558272
First received: November 13, 2007
Last updated: May 23, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Prostate Cancer
Bone Neoplasms
Drug: AZD0530
Drug: Zoledronic Acid
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Percentage Change From Baseline in Serum Beta C-terminal Cross-linking Telopeptide of Type I Collagen (betaCTX) at Week 4 [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 139
Study Start Date: February 2008
Study Completion Date: August 2012
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AZD0530 175 mg
AZD0530 (saracatinib) 175 mg once daily
Drug: AZD0530
Daily oral dose
Other Name: Saracatinib
Experimental: Zoledronic Acid 4 mg
Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period
Drug: Zoledronic Acid
Other Name: Zometa

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT00558272

  Show 28 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Richard Finkelman, DDS, PhD AstraZeneca
Principal Investigator: Meabe Aklilu, MD Wake Forest School of Medicine
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00558272     History of Changes
Other Study ID Numbers: D8180C00034
Study First Received: November 13, 2007
Results First Received: May 27, 2011
Last Updated: May 23, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Denmark: Danish Medicines Agency
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Norway: Norwegian Medicines Agency
Portugal: National Pharmacy and Medicines Institute
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:
breast cancer
prostate cancer
metastatic bone disease
Subjects with breast cancer or prostate cancer with metastatic bone disease

Additional relevant MeSH terms:
Prostatic Neoplasms
Breast Neoplasms
Bone Diseases
Bone Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Breast Diseases
Skin Diseases
Musculoskeletal Diseases
Zoledronic acid
Diphosphonates
Saracatinib
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014