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

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:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Bone Cancer Bone Diseases Breast Cancer Cancer Prostate Cancer

Drug Information available for: Zoledronic acid

U.S. FDA Resources

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
Estimated Study Completion Date:	December 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

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 University

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:	September 24, 2012
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:

Bone Diseases
Bone Neoplasms
Breast Neoplasms
Neoplasms
Prostatic Neoplasms
Musculoskeletal Diseases
Neoplasms by Site
Breast Diseases
Skin Diseases

Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Prostatic Diseases
Zoledronic acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 21, 2013