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

• uNTx (Corrected by Creatinine) < 50 Nmol/mmol at Week 25 [ Time Frame: 25 weeks ] [ Designated as safety issue: No ]
  Urinary N-telopeptide (uNTX) corrected by creatinine < 50 nmol/mmol at week 25.
• Percent Change of uNTx (Corrected by Creatinne) From Baseline to Week 25 [ Time Frame: Baseline, week 25 ] [ Designated as safety issue: No ]
  Percent change from baseline to week 25 urinary N-telopeptide (uNTX) calculated using ((week 25 value - baseline value) / baseline value ) x 100.
• Time to Reduction of uNTX (Corrected by Creatinine) to <50nmol/mmol [ Time Frame: Day 1, week 25 ] [ Designated as safety issue: No ]
  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.
• Duration of Maintaining uNTX (Corrected by Creatinine) < 50nmol/mmol [ Time Frame: Day 1, week 25 ] [ Designated as safety issue: No ]
  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.
• Percent Change of Serum CTX From Baseline to Week 25 [ Time Frame: Baseline, week 25 ] [ Designated as safety issue: No ]
  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.
• Time to First Skeletal Related Event [ Time Frame: Day 1, week 25 ] [ Designated as safety issue: No ]
  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).
• Skeletal Related Events [ Time Frame: Day 1, week 25 ] [ Designated as safety issue: No ]
  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).
• Hypercalcemia [ Time Frame: Day 1, week 25 ] [ Designated as safety issue: Yes ]
  Occurrence of hypercalcemia at grade 3 or 4 according to CTCAE v3 criteria

• Proportion of subjects achieving urinary N-Telopeptide levels less than 50 nM BCE / mM creatinine during the course of the study
• Time to reduction of urinary N-Telopeptide to less than 50 nM BCE/ mM creatinine
• Duration of urinary N-Telopeptide (uNTx) level less than 50 nM BCE / mM creatinine
• Percent change of C-Telopeptide (sCTx) from baseline to week 25
• Percent change of urinary N-Telopeptide (uNTx) from baseline to week 25
• Proportion of study subjects experiencing skeletal related events (SRE) and the time to first on study SRE. SRE will be defined as bone fracture, including vertebral fracture; surgery or radiation therapy to bone; spinal cord compression
• Incidence of hypercalcemia

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.

• 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

• Genetic: AMG 162 180 mg (SC) q 12 weeks
  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.
• Drug: IV Bisphosphonate q 4 weeks
  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.
• Genetic: AMG 162- 180 mg q 4 weeks
  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.

• Active Comparator: IV Bisphosphonates q 4 weeks
  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.
  Intervention: Drug: IV Bisphosphonate q 4 weeks
• Experimental: 180 mg AMG 162 (SC) q 12 weeks
  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.
  Intervention: Genetic: AMG 162 180 mg (SC) q 12 weeks
• Experimental: 180 mg AMG 162 (SC) q 4 weeks
  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.
  Intervention: Genetic: AMG 162- 180 mg q 4 weeks

• Fizazi K, Lipton A, Mariette X, Body JJ, Rahim Y, Gralow JR, Gao G, Wu L, Sohn W, Jun S. Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. J Clin Oncol. 2009 Apr 1;27(10):1564-71. Epub 2009 Feb 23.
• Fizazi K, Bosserman L, Gao G, Skacel T, Markus R. Denosumab treatment of prostate cancer with bone metastases and increased urine N-telopeptide levels after therapy with intravenous bisphosphonates: results of a randomized phase II trial. J Urol. 2009 Aug;182(2):509-15; discussion 515-6. Epub 2009 Jun 13.

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.