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

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Breast Cancer, Prostate Cancer, Bone Neoplasms

Intervention / Treatment
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* Drug: AZD0530
* Drug: Zoledronic Acid


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD0530 175 mg<br>AZD0530 (saracatinib) 175 mg once daily | Drug: AZD0530<br>* Daily oral dose<br>* Other names: Saracatinib;|
| Experimental: Zoledronic Acid 4 mg<br>Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period | Drug: Zoledronic Acid<br> <br> * Other names: Zometa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline to Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline to Week 4 | 
| 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. | Baseline to Week 4 | 
| 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. | Baseline to Week 4 | 
| 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. | Baseline to Week 4 | 
| 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. | Baseline to Week 4 | 
| 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. | Baseline to Week 4 | 
| 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. | Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, prostate cancer, metastatic bone disease, Subjects with breast cancer or prostate cancer with metastatic bone disease