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

Phase 2

Completed

Conditions: Breast Cancer
Prostate Cancer
Bone Neoplasms

Interventions: Drug: AZD0530
Drug: Zoledronic Acid

Registration Number: NCT00558272

Lead Sponsor: AstraZeneca

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 139

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AZD0530 175 mg	AZD0530	AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg	Zoledronic Acid	Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

Primary Outcome Measures

Name	Time	Method
Percentage Change From Baseline in Serum Beta C-terminal Cross-linking Telopeptide of Type I Collagen (betaCTX) at Week 4	Baseline to 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

Name	Time	Method
Percentage Change From Baseline in Serum Bone-specific Alkaline Phosphatase (bALP) at Week 4	Baseline to 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	Baseline to 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	Baseline to 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	Baseline to 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	Baseline to 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	Baseline to 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)	Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29	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)	Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
Saracatinib: Maximum Plasma Concentration at Steady State (Css,Max)	Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
Saracatinib: Minimum Plasma Concentration at Steady State (Css,Min)	Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
Saracatinib: Time to Cssmax (Tmax)	Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
N-desmethyl Metabolite of Saracatinib: Area Under the Curve at Steady State (AUCss)	Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
N-desmethyl Metabolite of Saracatinib: Maximum Plasma Concentration at Steady State (Css,Max)	Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
N-desmethyl Metabolite of Saracatinib: Minimum Plasma Concentration at Steady State (Css,Min)	Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
N-desmethyl Metabolite of Saracatinib: AUCss Metabolite to Parent Ratio	Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
N-desmethyl Metabolite of Saracatinib: Time to Cssmax (Tmax)	Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29