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

Study Overview
=================
Brief Summary
-----------------
The purpose of this trial is to determine the effectiveness of AMG 162 in reducing urinary N-telopeptide in advanced cancer subjects with bone metastases.

Official Title
-----------------
A Randomized, Open Label, Active Controlled Study of AMG 162 in Subjects With Advanced Cancer Currently Being Treated With Intravenous Bisphosphonates

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

Intervention / Treatment
-----------------
* Genetic: AMG 162 180 mg (SC) q 12 weeks
* Drug: IV Bisphosphonate q 4 weeks
* Genetic: AMG 162- 180 mg q 4 weeks


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients at least 18 years of age with histologically confirmed solid tumor carcinomas (except lung) or multiple myeloma Radiographic evidence of 1 or more bone lesions or lytic lesion in myeloma Currently receiving IV bisphosphonates Urinary N-Telopeptide (uNTx) greater than 50 nM BCE/mM creatinine Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2 Exclusion Criteria: More than 2 prior skeletal related events (SRE) Known brain metastases Prior history or current evidence of osteonecrosis/osteomyelitis of the jaw Active dental or jaw conditions which requires oral surgery Non-healed dental/oral surgery Prior administration of AMG 162 Evidence of impending fracture in weight bearing bones Pregnancy or breastfeeding. Subjects must be surgically sterile, postmenopausal, or must agree to use effective contraception during the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: IV Bisphosphonates q 4 weeks<br>This is an open-label randomization to receive IV bisphosphonate (administered per package insert) every 4 weeks during the treatment phase. If subjects are enrolled into the extension phase, they will receive AMG 162 180mg (SC) every 4 weeks. | Drug: IV Bisphosphonate q 4 weeks<br>* IV Bisphosphonate (eg pamidronate or zoledronic acid) every 4 weeks for 6 doses as described by package insert during the treatment phase. If enrolled to the extension phase, subject will be assigned to the AMG 162 180mg (SC) every 4 weeks for 26 doses.<br>|
| Experimental: 180 mg AMG 162 (SC) q 12 weeks<br>This is an open-label randomization to receive 180 mg AMG 162 (SC) every 12 weeks during the treatment phase. If subjects are enrolled into the extension phase, they will continue to receive 180 mg AMG 162 (SC) every 12 weeks. | Genetic: AMG 162 180 mg (SC) q 12 weeks<br>* A 180 mg AMG 162 (SC) administered every 12 weeks for 2 doses (Day 1 and wk 13) in the treatment phase. If subjected are enrolled in the extension phase, they will continue to receive a 180 mg AMG 162 (SC) administered every 12 weeks for 9 doses.<br>|
| Experimental: 180 mg AMG 162 (SC) q 4 weeks<br>This is an open-label randomization to receive 180 mg AMG 162 (SC) every 4 weeks during the treatment phase. If subject is enrolled into the extension phase, they will continue to receive 180 mg AMG 162 (SC) every 4 weeks. | Genetic: AMG 162- 180 mg q 4 weeks<br>* A 180 mg AMG 162 (SC) administered every 4 weeks for 6 doses in the treatment phase. If subjected are enrolled in the extension phase, they will continue to receive a 180 mg AMG 162 (SC) administered every 4 weeks for 26 doses.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| uNTx (Corrected by Creatinine) < 50 Nmol/mmol at Week 13 | Urinary N-telopeptide (uNTx) corrected by creatinine (uNTx/Cr) < 50 nmol/mmol at week 13. | 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| uNTx (Corrected by Creatinine) < 50 Nmol/mmol at Week 25 | Urinary N-telopeptide (uNTX) corrected by creatinine < 50 nmol/mmol at week 25. | 25 weeks | 
| Percent Change of uNTx (Corrected by Creatinne) From Baseline to Week 25 | Percent change from baseline to week 25 urinary N-telopeptide (uNTX) calculated using ((week 25 value - baseline value) / baseline value ) x 100. | Baseline, week 25 | 
| Time to Reduction of uNTX (Corrected by Creatinine) to <50nmol/mmol | Kaplan-Meier estimate of the median time from enrollment to the 1st occurrence of uNTx below 50 nmol BCE/mmol (corrected by creatinine) up to week 25. For participants whose uNTx does not go below 50 nM BCE/mM creatinine, the time is censored at time of last evaluation of uNTx by week 25. | Day 1, week 25 | 
| Duration of Maintaining uNTX (Corrected by Creatinine) < 50nmol/mmol | Time from the 1st occurrence of uNTx below 50 nmol BCE/mmol (corrected by creatinine) to the 1st occurrence of uNTx above 50 nmol BCE/mmol up to week 25. For participants who remained below 50 nmol BCE/mmol, the time is censored at the time of last evaluation of uNTx up to week 25. | Day 1, week 25 | 
| Percent Change of Serum CTX From Baseline to Week 25 | Percent change from baseline to week 25 in Type I serum C-Telopeptide (CTX), calculated using ((week 25 value - baseline value) / baseline value ) x 100. | Baseline, week 25 | 
| Time to First Skeletal Related Event | Time from study day 1 to first Skeletal Related Event (SRE), defined as >1 of the following: pathological bone fracture, spinal cord compression, surgery or radiation therapy to bone (including the use of radioisotopes). | Day 1, week 25 | 
| Skeletal Related Events | Skeletal Related Event (SRE), defined as >1 of the following: pathological bone fracture, spinal cord compression, surgery or radiation therapy to bone (including the use of radioisotopes). | Day 1, week 25 | 
| Hypercalcemia | Occurrence of hypercalcemia at grade 3 or 4 according to CTCAE v3 criteria | Day 1, week 25 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bone Metastases, AMG 162, Bisphosphonates, Solid Tumor Carcinomas, Advanced