Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Musculoskeletal Diseases

Rare Diseases

Breast Neoplasms

Neoplasm Metastasis

Prostatic Neoplasms

Carcinoma

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms, Second Primary

Bone Neoplasms

Bone Marrow Diseases

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Neoplastic Processes

Bone Diseases

Bone Density Conservation Agents

All Drugs and Chemicals

Zoledronic Acid

Denosumab

Diphosphonates

Pamidronate

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.

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.

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.

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.

AMG 162 180 mg (SC) q 12 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.

IV Bisphosphonate 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.

AMG 162- 180 mg q 4 weeks

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.

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

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

Urinary N-telopeptide (uNTx) corrected by creatinine (uNTx/Cr) \< 50 nmol/mmol at week 13.

Urinary N-telopeptide (uNTX) corrected by creatinine \< 50 nmol/mmol at week 25.

Percent change from baseline to week 25 urinary N-telopeptide (uNTX) calculated using ((week 25 value - baseline value) / baseline value ) x 100.

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.

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 from baseline to week 25 in Type I serum C-Telopeptide (CTX), calculated using ((week 25 value - baseline value) / baseline value ) x 100.

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 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).

Occurrence of hypercalcemia at grade 3 or 4 according to CTCAE v3 criteria

Amgen

Global Development Leader

The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.

Bisphosphonate IV Q4W

Denosumab 180 mg Q12W

Denosumab 180 mg Q4W

Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)

Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)

Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)

Total

Age Continuous

Sex: Female, Male

White or Caucasian

Black or African American

Hispanic or Latino

Asian

Native Hawaiian or Other Pacific Islander

Other

Race/Ethnicity, Customized

Breast cancer

Prostate cancer

Mutiple myeloma

Other solid tumor

Cancer Type Stratification Factor

Corrected for urine creatinine (uNTx/Creatinine)

Urinary N-telopeptide (uNTx) Level

Serum C-Telopeptide (CTx)

Study Director

All participants who are randomized to the treatment phase, receive at least one dose of treatment phase investigational product, and have treatment phase baseline measurements of uNTx and at least one treatment phase post-baseline measurement of uNTx.

uNTx (Corrected by Creatinine) < 50 Nmol/mmol at Week 13

uNTx (Corrected by Creatinine) < 50 Nmol/mmol at Week 25

Percent Change of uNTx (Corrected by Creatinne) From Baseline to Week 25

Time to Reduction of uNTX (Corrected by Creatinine) to <50nmol/mmol

Treatment Phase Primary Analysis Subset. Median was not reached in at least 1 treatment arm. In lieu of the median, the number of subject whose uNTX (corrected by creatinine) less than 50nmol/mmol is presented.

Duration of Maintaining uNTX (Corrected by Creatinine) < 50nmol/mmol

All participants who are randomized to the treatment phase, receive at least one dose of treatment phase investigational product, and have treatment phase baseline measurements of uNTx and at least one treatment phase post-baseline measurement of uNTx and had available data.

Percent Change of Serum CTX From Baseline to Week 25

All participants exposed to investigational product during the treatment phase. Median was not reached in at least 1 treatment arm. In lieu of the median, the number of subject who experienced a skeletal related event is presented.

Time to First Skeletal Related Event

All participants exposed to investigational product during the treatment phase.

Skeletal Related Events

Hypercalcemia

Treatment Period (25 Weeks)

Follow-up Period

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Hormones

120 mg SC injection of denosumab Q4W until the subject has access to commercially available product or for up to 2 years, which ever comes first.

amg 162

The purpose of this study is to describe the safety and tolerability of denosumab administration as measured by adverse events, immunogenicity, and safety laboratory parameters in subjects who previously received either zoledronic acid (Zometa®) or denosumab.

Open Label Extension to SRE Studies in United Kingdom and Czech Republic Only

An Open Label, Single Arm, Extension Study to Evaluate the Long Term Safety of Denosumab in the Treatment of Bone Metastases in Subjects With Advanced Cancer or Multiple Myeloma

This cohort received Zoledronic Acid 4 mg Q4W in the blinded treatment phase of the parent study 20050103 (NCT00321620) or 20050136 (NCT00321464), and received Denosumab 120 mg Q4W in this open-label extension study.

Zoledronic Acid 4 mg Q4W / Denosumab 120 mg Q4W

This cohort received Denosumab 120 mg Q4W in the blinded treatment phase of the parent study 20050103 (NCT00321620) or 20050136 (NCT00321464), and received Denosumab 120 mg Q4W in this open-label extension study.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of AMG 162 in Subjects With Advanced Cancer Currently Being Treated With Intravenous (IV) Bisphosphonates	NCT00104650	Bone Metastases... Bone Metastases... Bone Metastases...	AMG 162 180 mg ... IV Bisphosphona... AMG 162- 180 mg...	18 Years -	Amgen
Open Label Extension to SRE Studies in United Kingdom and Czech Republic Only	NCT00950911	Bone Metastases... Bone Metastases... Bone Metastases...	amg 162	18 Years -	Amgen
Study of AMG 162 in Subjects With Advanced Cancer Currently Being Treated With Intravenous (IV) Bisphosphonates	NCT00104650	Bone Metastases... Bone Metastases... Bone Metastases...	AMG 162 180 mg ... IV Bisphosphona... AMG 162- 180 mg...	18 Years -	Amgen
Open Label Extension to SRE Studies in United Kingdom and Czech Republic Only	NCT00950911	Bone Metastases... Bone Metastases... Bone Metastases...	amg 162	18 Years -	Amgen

Spots Global Cancer Trial Database for bone metastases in subjects with advanced cancer or multiple myeloma