Study of AMG 162 in Subjects With Advanced Cancer Currently Being Treated With Intravenous (IV) Bisphosphonates

This study has been completed.
Sponsor:
Information provided by:
Amgen
ClinicalTrials.gov Identifier:
NCT00104650
First received: March 3, 2005
Last updated: January 20, 2011
Last verified: January 2011
Results First Received: December 9, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Bone Metastases in Men With Hormone-Refractory Prostate Cancer
Bone Metastases in Subjects With Advanced Breast Cancer
Bone Metastases in Subjects With Advanced Cancer or Multiple Myeloma
Interventions: Genetic: AMG 162 180 mg (SC) q 12 weeks
Drug: IV Bisphosphonate q 4 weeks
Genetic: AMG 162- 180 mg q 4 weeks

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were enrolled from 2 December 2004 through 30 March 2007

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Bisphosphonate IV Q4W Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)
Denosumab 180 mg Q12W Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)
Denosumab 180 mg Q4W Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)

Participant Flow for 2 periods

Period 1:   Treatment Period (25 Weeks)
    Bisphosphonate IV Q4W     Denosumab 180 mg Q12W     Denosumab 180 mg Q4W  
STARTED     37     36     38  
Received Investigational Product     35     35     38  
COMPLETED     25     25     28  
NOT COMPLETED     12     11     10  
Physician Decision                 0                 0                 1  
Withdrawal by Subject                 2                 1                 1  
Death                 7                 5                 6  
Disease progression                 2                 3                 2  
Ineligibility determined                 0                 1                 0  
Other                 1                 0                 0  
Protocol deviation                 0                 1                 0  

Period 2:   Follow-up Period
    Bisphosphonate IV Q4W     Denosumab 180 mg Q12W     Denosumab 180 mg Q4W  
STARTED     25     25     28  
COMPLETED     14     12     18  
NOT COMPLETED     11     13     10  
Physician Decision                 1                 1                 0  
Adverse Event                 1                 0                 1  
Withdrawal by Subject                 0                 3                 3  
Death                 6                 6                 4  
Disease progression                 3                 1                 0  
Lost to Follow-up                 0                 1                 2  
Other                 0                 1                 0  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Denosumab 180 mg Q4W Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)
Bisphosphonate IV Q4W Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)
Denosumab 180 mg Q12W Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)
Total Total of all reporting groups

Baseline Measures
    Denosumab 180 mg Q4W     Bisphosphonate IV Q4W     Denosumab 180 mg Q12W     Total  
Number of Participants  
[units: participants]
  38     37     36     111  
Age  
[units: Years]
Mean ± Standard Deviation
  60.6  ± 10.7     61.6  ± 11.7     65.3  ± 12.7     62.5  ± 11.8  
Gender  
[units: Participants]
       
Female     19     18     19     56  
Male     19     19     17     55  
Race/Ethnicity, Customized  
[units: Participants]
       
White or Caucasian     22     22     19     63  
Black or African American     0     0     1     1  
Hispanic or Latino     16     13     15     44  
Asian     0     1     0     1  
Native Hawaiian or Other Pacific Islander     0     1     0     1  
Other     0     0     1     1  
Cancer Type Stratification Factor  
[units: Participants]
       
Breast cancer     16     16     14     46  
Prostate cancer     17     17     16     50  
Mutiple myeloma     2     3     4     9  
Other solid tumor     3     1     2     6  
Urinary N-telopeptide (uNTx) Level [1]
[units: nmol/mmol]
Mean ± Standard Deviation
  149.94  ± 147.20     149.88  ± 176.28     175.15  ± 208.87     158.01  ± 177.11  
Serum C-Telopeptide (CTx)  
[units: ng/mL]
Mean ± Standard Deviation
  1.12  ± 1.18     1.40  ± 1.93     1.34  ± 1.27     1.28  ± 1.48  
[1] Corrected for urine creatinine (uNTx/Creatinine)



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   uNTx (Corrected by Creatinine) < 50 Nmol/mmol at Week 13   [ Time Frame: 13 weeks ]

2.  Secondary:   uNTx (Corrected by Creatinine) < 50 Nmol/mmol at Week 25   [ Time Frame: 25 weeks ]

3.  Secondary:   Percent Change of uNTx (Corrected by Creatinne) From Baseline to Week 25   [ Time Frame: Baseline, week 25 ]

4.  Secondary:   Time to Reduction of uNTX (Corrected by Creatinine) to <50nmol/mmol   [ Time Frame: Day 1, week 25 ]

5.  Secondary:   Duration of Maintaining uNTX (Corrected by Creatinine) < 50nmol/mmol   [ Time Frame: Day 1, week 25 ]

6.  Secondary:   Percent Change of Serum CTX From Baseline to Week 25   [ Time Frame: Baseline, week 25 ]

7.  Secondary:   Time to First Skeletal Related Event   [ Time Frame: Day 1, week 25 ]

8.  Secondary:   Skeletal Related Events   [ Time Frame: Day 1, week 25 ]

9.  Secondary:   Hypercalcemia   [ Time Frame: Day 1, week 25 ]


  Serious Adverse Events
  Hide Serious Adverse Events

Time Frame 25 weeks
Additional Description The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.

Reporting Groups
  Description
Bisphosphonate IV Q4W No text entered.
Denosumab 180 mg Q12W No text entered.
Denosumab 180 mg Q4W No text entered.

Serious Adverse Events
    Bisphosphonate IV Q4W     Denosumab 180 mg Q12W     Denosumab 180 mg Q4W  
Total, serious adverse events        
# participants affected / at risk     19/35 (54.29%)     16/35 (45.71%)     21/38 (55.26%)  
Blood and lymphatic system disorders        
Anaemia † 1      
# participants affected / at risk     4/35 (11.43%)     4/35 (11.43%)     4/38 (10.53%)  
Bone marrow failure † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Coagulopathy † 1      
# participants affected / at risk     0/35 (0.00%)     0/35 (0.00%)     1/38 (2.63%)  
Leukopenia † 1      
# participants affected / at risk     2/35 (5.71%)     0/35 (0.00%)     0/38 (0.00%)  
Neutropenia † 1      
# participants affected / at risk     2/35 (5.71%)     2/35 (5.71%)     2/38 (5.26%)  
Thrombocytopenia † 1      
# participants affected / at risk     2/35 (5.71%)     2/35 (5.71%)     3/38 (7.89%)  
Cardiac disorders        
Cardio-respiratory arrest † 1      
# participants affected / at risk     0/35 (0.00%)     0/35 (0.00%)     1/38 (2.63%)  
Cardiopulmonary failure † 1      
# participants affected / at risk     2/35 (5.71%)     0/35 (0.00%)     0/38 (0.00%)  
Pericardial effusion † 1      
# participants affected / at risk     0/35 (0.00%)     1/35 (2.86%)     0/38 (0.00%)  
Sinus bradycardia † 1      
# participants affected / at risk     0/35 (0.00%)     0/35 (0.00%)     1/38 (2.63%)  
Eye disorders        
Diplopia † 1      
# participants affected / at risk     0/35 (0.00%)     0/35 (0.00%)     1/38 (2.63%)  
Gastrointestinal disorders        
Abdominal distension † 1      
# participants affected / at risk     0/35 (0.00%)     0/35 (0.00%)     1/38 (2.63%)  
Ascites † 1      
# participants affected / at risk     0/35 (0.00%)     1/35 (2.86%)     0/38 (0.00%)  
Constipation † 1      
# participants affected / at risk     0/35 (0.00%)     2/35 (5.71%)     0/38 (0.00%)  
Diarrhoea † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Nausea † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Stomatitis † 1      
# participants affected / at risk     2/35 (5.71%)     0/35 (0.00%)     0/38 (0.00%)  
Subileus † 1      
# participants affected / at risk     0/35 (0.00%)     1/35 (2.86%)     0/38 (0.00%)  
Upper gastrointestinal haemorrhage † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     1/38 (2.63%)  
General disorders        
Death † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
General physical health deterioration † 1      
# participants affected / at risk     1/35 (2.86%)     3/35 (8.57%)     1/38 (2.63%)  
Obstruction † 1      
# participants affected / at risk     0/35 (0.00%)     0/35 (0.00%)     1/38 (2.63%)  
Pain † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Pyrexia † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     1/38 (2.63%)  
Hepatobiliary disorders        
Cholangitis acute † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Hepatic failure † 1      
# participants affected / at risk     0/35 (0.00%)     1/35 (2.86%)     1/38 (2.63%)  
Hepatomegaly † 1      
# participants affected / at risk     0/35 (0.00%)     1/35 (2.86%)     0/38 (0.00%)  
Infections and infestations        
Bronchopneumonia † 1      
# participants affected / at risk     0/35 (0.00%)     0/35 (0.00%)     1/38 (2.63%)  
Catheter related infection † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Lung infection † 1      
# participants affected / at risk     2/35 (5.71%)     1/35 (2.86%)     0/38 (0.00%)  
Pneumonia † 1      
# participants affected / at risk     2/35 (5.71%)     1/35 (2.86%)     1/38 (2.63%)  
Pneumonia bacterial † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Staphylococcal sepsis † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Urinary tract infection staphylococcal † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Injury, poisoning and procedural complications        
Brain contusion † 1      
# participants affected / at risk     0/35 (0.00%)     1/35 (2.86%)     0/38 (0.00%)  
Femoral neck fracture † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Subdural haematoma † 1      
# participants affected / at risk     0/35 (0.00%)     2/35 (5.71%)     1/38 (2.63%)  
Metabolism and nutrition disorders        
Anorexia † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Cachexia † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Dehydration † 1      
# participants affected / at risk     1/35 (2.86%)     2/35 (5.71%)     0/38 (0.00%)  
Hypercalcaemia † 1      
# participants affected / at risk     0/35 (0.00%)     1/35 (2.86%)     0/38 (0.00%)  
Hypocalcaemia † 1      
# participants affected / at risk     0/35 (0.00%)     0/35 (0.00%)     1/38 (2.63%)  
Hypophosphataemia † 1      
# participants affected / at risk     0/35 (0.00%)     0/35 (0.00%)     1/38 (2.63%)  
Musculoskeletal and connective tissue disorders        
Back pain † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Bone pain † 1      
# participants affected / at risk     3/35 (8.57%)     2/35 (5.71%)     1/38 (2.63%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)        
Breast cancer † 1      
# participants affected / at risk     0/35 (0.00%)     1/35 (2.86%)     1/38 (2.63%)  
Malignant neoplasm progression † 1      
# participants affected / at risk     0/35 (0.00%)     0/35 (0.00%)     1/38 (2.63%)  
Metastases to bone † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Metastases to central nervous system † 1      
# participants affected / at risk     3/35 (8.57%)     0/35 (0.00%)     2/38 (5.26%)  
Metastases to liver † 1      
# participants affected / at risk     0/35 (0.00%)     1/35 (2.86%)     0/38 (0.00%)  
Metastases to lung † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Metastases to meninges † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     1/38 (2.63%)  
Metastasis † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Multiple myeloma † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Prostate cancer † 1      
# participants affected / at risk     2/35 (5.71%)     2/35 (5.71%)     3/38 (7.89%)  
Prostate cancer metastatic † 1      
# participants affected / at risk     0/35 (0.00%)     0/35 (0.00%)     1/38 (2.63%)  
Thyroid cancer † 1      
# participants affected / at risk     0/35 (0.00%)     1/35 (2.86%)     0/38 (0.00%)  
Vaginal cancer metastatic † 1      
# participants affected / at risk     0/35 (0.00%)     1/35 (2.86%)     0/38 (0.00%)  
Nervous system disorders        
Areflexia † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Cerebral haemorrhage † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     1/38 (2.63%)  
Cerebrovascular accident † 1      
# participants affected / at risk     0/35 (0.00%)     1/35 (2.86%)     0/38 (0.00%)  
Epiduritis † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Facial paresis † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Loss of consciousness † 1      
# participants affected / at risk     0/35 (0.00%)     0/35 (0.00%)     1/38 (2.63%)  
Spinal cord compression † 1      
# participants affected / at risk     2/35 (5.71%)     0/35 (0.00%)     0/38 (0.00%)  
Psychiatric disorders        
Anxiety † 1      
# participants affected / at risk     0/35 (0.00%)     0/35 (0.00%)     1/38 (2.63%)  
Confusional state † 1      
# participants affected / at risk     2/35 (5.71%)     1/35 (2.86%)     0/38 (0.00%)  
Hallucination † 1      
# participants affected / at risk     0/35 (0.00%)     1/35 (2.86%)     0/38 (0.00%)  
Renal and urinary disorders        
Dysuria † 1      
# participants affected / at risk     0/35 (0.00%)     0/35 (0.00%)     1/38 (2.63%)  
Haematuria † 1      
# participants affected / at risk     0/35 (0.00%)     0/35 (0.00%)     1/38 (2.63%)  
Kidney enlargement † 1      
# participants affected / at risk     0/35 (0.00%)     0/35 (0.00%)     1/38 (2.63%)  
Renal failure † 1      
# participants affected / at risk     1/35 (2.86%)     1/35 (2.86%)     1/38 (2.63%)  
Renal failure acute † 1      
# participants affected / at risk     0/35 (0.00%)     1/35 (2.86%)     0/38 (0.00%)  
Renal tubular necrosis † 1      
# participants affected / at risk     0/35 (0.00%)     0/35 (0.00%)     1/38 (2.63%)  
Urinary retention † 1      
# participants affected / at risk     0/35 (0.00%)     0/35 (0.00%)     1/38 (2.63%)  
Respiratory, thoracic and mediastinal disorders        
Acute pulmonary oedema † 1      
# participants affected / at risk     0/35 (0.00%)     1/35 (2.86%)     0/38 (0.00%)  
Acute respiratory distress syndrome † 1      
# participants affected / at risk     0/35 (0.00%)     0/35 (0.00%)     1/38 (2.63%)  
Asthma † 1      
# participants affected / at risk     0/35 (0.00%)     1/35 (2.86%)     0/38 (0.00%)  
Dyspnoea † 1      
# participants affected / at risk     0/35 (0.00%)     1/35 (2.86%)     1/38 (2.63%)  
Pleurisy † 1      
# participants affected / at risk     0/35 (0.00%)     1/35 (2.86%)     0/38 (0.00%)  
Pulmonary embolism † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Respiratory distress † 1      
# participants affected / at risk     2/35 (5.71%)     0/35 (0.00%)     0/38 (0.00%)  
Skin and subcutaneous tissue disorders        
Scar † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Surgical and medical procedures        
Radiotherapy to bone † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Vascular disorders        
Hypertension † 1      
# participants affected / at risk     0/35 (0.00%)     1/35 (2.86%)     0/38 (0.00%)  
Neurogenic shock † 1      
# participants affected / at risk     1/35 (2.86%)     0/35 (0.00%)     0/38 (0.00%)  
Thrombosis † 1      
# participants affected / at risk     0/35 (0.00%)     0/35 (0.00%)     1/38 (2.63%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 10.0




  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information