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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00558272
Recruitment Status : Completed
First Posted : November 14, 2007
Results First Posted : June 27, 2011
Last Update Posted : May 27, 2013
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Breast Cancer
Prostate Cancer
Bone Neoplasms
Interventions Drug: AZD0530
Drug: Zoledronic Acid
Enrollment 139
Recruitment Details Randomised=full analysis set: AZD0530 175mg=69, Zoledronic acid 4mg=70; safety set: AZD0530 175mg=68, Zoledronic acid 4mg=69
Pre-assignment Details  
Arm/Group Title AZD0530 175 mg Zoledronic Acid 4 mg
Hide Arm/Group Description AZD0530 (saracatinib) 175 mg once daily Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period
Period Title: Overall Study
Started 69 [1] 70 [1]
30 Days Follow-up 41 [2] 67 [2]
Completed 56 [3] 68 [3]
Not Completed 13 2
Reason Not Completed
Adverse Event             10             0
Death             1             0
Dev. of study specific discon. criteria             1             0
AZ study team decision             0             1
Incorrectly enrolled             1             0
Withdrawal by Subject             0             1
[1]
Randomised
[2]
30 days after last dose
[3]
4-week treatment period
Arm/Group Title AZD0530 175 mg Zoledronic Acid 4 mg Total
Hide Arm/Group Description AZD0530 (saracatinib) 175 mg once daily Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period Total of all reporting groups
Overall Number of Baseline Participants 69 70 139
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 69 participants 70 participants 139 participants
67.6  (8.35) 67.3  (11.58) 67.4  (10.07)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 69 participants 70 participants 139 participants
Female
11
  15.9%
12
  17.1%
23
  16.5%
Male
58
  84.1%
58
  82.9%
116
  83.5%
1.Primary Outcome
Title Percentage Change From Baseline in Serum Beta C-terminal Cross-linking Telopeptide of Type I Collagen (betaCTX) at Week 4
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The number of participants analyzed reflected the number of paired serum samples per participant that yielded valid assay results, not the total number of participants or completers. The number of evaluable paired serum samples will therefore be a subset of the total number of participants.
Arm/Group Title AZD0530 175 mg Zoledronic Acid 4 mg
Hide Arm/Group Description:
AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period
Overall Number of Participants Analyzed 46 65
Geometric Mean (95% Confidence Interval)
Unit of Measure: Percentage change in betaCTX
-71.1
(-75.9 to -65.4)
-68.4
(-73.0 to -63.2)
2.Secondary Outcome
Title Percentage Change From Baseline in Serum Bone-specific Alkaline Phosphatase (bALP) at Week 4
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The number of participants analyzed reflected the number of paired serum samples per participant that yielded valid assay results, not the total number of participants or completers. The number of evaluable paired serum samples will therefore be a subset of the total number of participants.
Arm/Group Title AZD0530 175 mg Zoledronic Acid 4 mg
Hide Arm/Group Description:
AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period
Overall Number of Participants Analyzed 48 66
Geometric Mean (95% Confidence Interval)
Unit of Measure: Percentage change in bALP
-13.2
(-24.4 to -0.3)
-3.1
(-13.9 to 9.1)
3.Secondary Outcome
Title Percentage Change From Baseline in Serum Cross-linked C-terminal Telopeptide of Type I Collagen (ICTP) at Week 4
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The number of participants analyzed reflected the number of paired serum samples per participant that yielded valid assay results, not the total number of participants or completers. The number of evaluable paired serum samples will therefore be a subset of the total number of participants.
Arm/Group Title AZD0530 175 mg Zoledronic Acid 4 mg
Hide Arm/Group Description:
AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period
Overall Number of Participants Analyzed 47 66
Geometric Mean (95% Confidence Interval)
Unit of Measure: Percentage change in ICTP
-40.2
(-46.3 to -33.4)
7.4
(-2.0 to 17.7)
4.Secondary Outcome
Title Percentage Change From Baseline in Serum N-terminal Propeptide of Type I Procollagen (PINP) at Week 4
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The number of participants analyzed reflected the number of paired serum samples per participant that yielded valid assay results, not the total number of participants or completers. The number of evaluable paired serum samples will therefore be a subset of the total number of participants.
Arm/Group Title AZD0530 175 mg Zoledronic Acid 4 mg
Hide Arm/Group Description:
AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period
Overall Number of Participants Analyzed 48 66
Geometric Mean (95% Confidence Interval)
Unit of Measure: Percentage change in PINP
-26.1
(-36.0 to -14.7)
-29.5
(-37.7 to -20.3)
5.Secondary Outcome
Title Percentage Change From Baseline in Serum Tartrate-resistant Acid Phosphatase 5b (TRAP5b) at Week 4
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The number of participants analyzed reflected the number of paired serum samples per participant that yielded valid assay results, not the total number of participants or completers. The number of evaluable paired serum samples will therefore be a subset of the total number of participants.
Arm/Group Title AZD0530 175 mg Zoledronic Acid 4 mg
Hide Arm/Group Description:
AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period
Overall Number of Participants Analyzed 48 65
Geometric Mean (95% Confidence Interval)
Unit of Measure: Percentage change in TRAP5b
-36.9
(-42.7 to -30.4)
-43.4
(-48.0 to -38.4)
6.Secondary Outcome
Title Percentage Change From Baseline in Urine N-terminal Cross-linking Telopeptide of Type I Collagen Normalised to Creatinine (NTx/Cr) at Week 4
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The number of participants analyzed reflected the number of paired serum samples per participant that yielded valid assay results, not the total number of participants or completers. The number of evaluable paired serum samples will therefore be a subset of the total number of participants.
Arm/Group Title AZD0530 175 mg Zoledronic Acid 4 mg
Hide Arm/Group Description:
AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period
Overall Number of Participants Analyzed 46 62
Geometric Mean (95% Confidence Interval)
Unit of Measure: Percentage change in NTx/Cr
-57.2
(-65.7 to -46.6)
-70.1
(-75.4 to -63.8)
7.Secondary Outcome
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The number of participants analyzed reflected the number of paired serum samples per participant that yielded valid assay results, not the total number of participants or completers. The number of evaluable paired serum samples will therefore be a subset of the total number of participants.
Arm/Group Title AZD0530 175 mg Zoledronic Acid 4 mg
Hide Arm/Group Description:
AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period
Overall Number of Participants Analyzed 41 49
Geometric Mean (95% Confidence Interval)
Unit of Measure: Percentage change in aaCTx/Cr
-68.2
(-76.7 to -56.5)
-82.8
(-87.1 to -77.0)
8.Secondary Outcome
Title Saracatinib: Area Under the Curve at Steady State (AUCss)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD0530 175 mg Zoledronic Acid 4 mg
Hide Arm/Group Description:
AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period
Overall Number of Participants Analyzed 51 0
Median (Full Range)
Unit of Measure: ng•hr/ml
7261
(3960 to 21500)
9.Secondary Outcome
Title Saracatinib: Plasma Clearance at Steady State (CLss/F)
Hide Description [Not Specified]
Time Frame Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD0530 175 mg Zoledronic Acid 4 mg
Hide Arm/Group Description:
AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period
Overall Number of Participants Analyzed 51 0
Median (Full Range)
Unit of Measure: L/h
24.10
(8.15 to 44.2)
10.Secondary Outcome
Title Saracatinib: Maximum Plasma Concentration at Steady State (Css,Max)
Hide Description [Not Specified]
Time Frame Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD0530 175 mg Zoledronic Acid 4 mg
Hide Arm/Group Description:
AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period
Overall Number of Participants Analyzed 51 0
Median (Full Range)
Unit of Measure: ng/ml
396.0
(190 to 1170)
11.Secondary Outcome
Title Saracatinib: Minimum Plasma Concentration at Steady State (Css,Min)
Hide Description [Not Specified]
Time Frame Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD0530 175 mg Zoledronic Acid 4 mg
Hide Arm/Group Description:
AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period
Overall Number of Participants Analyzed 51 0
Median (Full Range)
Unit of Measure: ng/ml
229.0
(99.1 to 770)
12.Secondary Outcome
Title Saracatinib: Time to Cssmax (Tmax)
Hide Description [Not Specified]
Time Frame Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD0530 175 mg Zoledronic Acid 4 mg
Hide Arm/Group Description:
AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period
Overall Number of Participants Analyzed 51 0
Median (Full Range)
Unit of Measure: h
4.0
(2 to 9)
13.Secondary Outcome
Title N-desmethyl Metabolite of Saracatinib: Area Under the Curve at Steady State (AUCss)
Hide Description [Not Specified]
Time Frame Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD0530 175 mg Zoledronic Acid 4 mg
Hide Arm/Group Description:
AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period
Overall Number of Participants Analyzed 51 0
Median (Full Range)
Unit of Measure: ng.h/ml
1069
(529 to 5100)
14.Secondary Outcome
Title N-desmethyl Metabolite of Saracatinib: Maximum Plasma Concentration at Steady State (Css,Max)
Hide Description [Not Specified]
Time Frame Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD0530 175 mg Zoledronic Acid 4 mg
Hide Arm/Group Description:
AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period
Overall Number of Participants Analyzed 51 0
Median (Full Range)
Unit of Measure: ng/ml
62.80
(25.3 to 253)
15.Secondary Outcome
Title N-desmethyl Metabolite of Saracatinib: Minimum Plasma Concentration at Steady State (Css,Min)
Hide Description [Not Specified]
Time Frame Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD0530 175 mg Zoledronic Acid 4 mg
Hide Arm/Group Description:
AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period
Overall Number of Participants Analyzed 51 0
Median (Full Range)
Unit of Measure: ng/ml
34.30
(16.6 to 230)
16.Secondary Outcome
Title N-desmethyl Metabolite of Saracatinib: AUCss Metabolite to Parent Ratio
Hide Description [Not Specified]
Time Frame Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD0530 175 mg Zoledronic Acid 4 mg
Hide Arm/Group Description:
AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period
Overall Number of Participants Analyzed 51 0
Median (Full Range)
Unit of Measure: Ratio
0.1420
(0.081 to 0.354)
17.Secondary Outcome
Title N-desmethyl Metabolite of Saracatinib: Time to Cssmax (Tmax)
Hide Description [Not Specified]
Time Frame Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD0530 175 mg Zoledronic Acid 4 mg
Hide Arm/Group Description:
AZD0530 (saracatinib) 175 mg once daily
Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period
Overall Number of Participants Analyzed 51 0
Median (Full Range)
Unit of Measure: h
2.0
(2 to 9)
Time Frame [Not Specified]
Adverse Event Reporting Description safety set: AZD0530 175mg=68, Zoledronic acid 4mg=69
 
Arm/Group Title AZD0530 175 mg Zoledronic Acid 4 mg
Hide Arm/Group Description AZD0530 (saracatinib) 175 mg once daily Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period
All-Cause Mortality
AZD0530 175 mg Zoledronic Acid 4 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
AZD0530 175 mg Zoledronic Acid 4 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   11/68 (16.18%)   4/69 (5.80%) 
Blood and lymphatic system disorders     
Anaemia  1  1/68 (1.47%)  0/69 (0.00%) 
Cardiac disorders     
Cardiac Arrest  1  1/68 (1.47%)  0/69 (0.00%) 
Myocardial Infarction  1  1/68 (1.47%)  0/69 (0.00%) 
Gastrointestinal disorders     
Vomiting  1  1/68 (1.47%)  0/69 (0.00%) 
General disorders     
General Physical Health Deterioration  1  0/68 (0.00%)  1/69 (1.45%) 
Pyrexia  1  1/68 (1.47%)  0/69 (0.00%) 
Infections and infestations     
Pneumonia  1  2/68 (2.94%)  0/69 (0.00%) 
Viral Infection  1  1/68 (1.47%)  0/69 (0.00%) 
Injury, poisoning and procedural complications     
Blood Creatinine Increased  1  0/68 (0.00%)  1/69 (1.45%) 
Metabolism and nutrition disorders     
Dehydration  1  0/68 (0.00%)  1/69 (1.45%) 
Musculoskeletal and connective tissue disorders     
Bone Pain  1  0/68 (0.00%)  1/69 (1.45%) 
Muscle Spasms  1  0/68 (0.00%)  1/69 (1.45%) 
Musculoskeletal Pain  1  0/68 (0.00%)  1/69 (1.45%) 
Nervous system disorders     
Cerebral Haemorrhage  1  1/68 (1.47%)  0/69 (0.00%) 
Renal and urinary disorders     
Renal Failure  1  1/68 (1.47%)  0/69 (0.00%) 
Renal Failure Acute  1  1/68 (1.47%)  0/69 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary Oedema  1  1/68 (1.47%)  0/69 (0.00%) 
Vascular disorders     
Deep Vein Thrombosis  1  1/68 (1.47%)  0/69 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
AZD0530 175 mg Zoledronic Acid 4 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   51/68 (75.00%)   46/69 (66.67%) 
Gastrointestinal disorders     
Nausea  1  16/68 (23.53%)  3/69 (4.35%) 
Diarrhoea  1  13/68 (19.12%)  4/69 (5.80%) 
Constipation  1  10/68 (14.71%)  5/69 (7.25%) 
Vomiting  1  7/68 (10.29%)  5/69 (7.25%) 
General disorders     
Influenza Like Illness  1  3/68 (4.41%)  8/69 (11.59%) 
Pyrexia  1  4/68 (5.88%)  6/69 (8.70%) 
Fatigue  1  5/68 (7.35%)  4/69 (5.80%) 
Asthenia  1  4/68 (5.88%)  1/69 (1.45%) 
Oedema Peripheral  1  4/68 (5.88%)  2/69 (2.90%) 
Infections and infestations     
Influenza  1  0/68 (0.00%)  11/69 (15.94%) 
Urinary Tract Infection  1  6/68 (8.82%)  2/69 (2.90%) 
Metabolism and nutrition disorders     
Decreased Appetite  1  8/68 (11.76%)  1/69 (1.45%) 
Musculoskeletal and connective tissue disorders     
Pain In Extremity  1  1/68 (1.47%)  7/69 (10.14%) 
Back Pain  1  8/68 (11.76%)  4/69 (5.80%) 
Musculoskeletal Pain  1  5/68 (7.35%)  8/69 (11.59%) 
Arthralgia  1  4/68 (5.88%)  7/69 (10.14%) 
Bone Pain  1  3/68 (4.41%)  5/69 (7.25%) 
Neck Pain  1  1/68 (1.47%)  4/69 (5.80%) 
Nervous system disorders     
Headache  1  5/68 (7.35%)  5/69 (7.25%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  5/68 (7.35%)  2/69 (2.90%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
Non-compliant patients were excluded from the biomarker analysis, in order to accurately assess effects due to treatment. The compliance criteria did not apply to the zoledronic acid arm, which led to an imbalance in the number of subjects analysed.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If a Study Site, or an investigator, requests permission to publish data from this study, any such publication (including oral presentations) is to be agreed with AstraZeneca prior to publication.
Results Point of Contact
Name/Title: Gerard Lynch
Organization: AstraZeneca
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00558272     History of Changes
Other Study ID Numbers: D8180C00034
First Submitted: November 13, 2007
First Posted: November 14, 2007
Results First Submitted: May 27, 2011
Results First Posted: June 27, 2011
Last Update Posted: May 27, 2013