A Study to Compare Denosumab With Zoledronic Acid in Subjects With Bone Metastases From Solid Tumors

Inclusion Criteria:

• Subject understands the nature and purpose of this study and the study procedures,which have been explained by the Investigator or delegate, and subject has signed thewritten informed consent for the overall study. The subject must sign a separatewritten informed consent to be eligible for enrolment in the pharmacokinetic substudy.

• Adult (aged >=18 years) of Asian ancestry with a histologically or cytologicallyconfirmed solid tumor. In addition, subjects who are enrolled at a center in mainlandChina or at an SFDA-certified center in Hong Kong including the approximately 33subjects in the pharmacokinetic substudy must be of Chinese race, ancestry, orheritage. Subjects enrolled in other regions or countries, such as Taiwan andSingapore, or at a non-SFDA-certified center in Hong Kong, are not required to be ofChinese race or ancestry.

• Current or prior documented radiographic evidence (i.e., x-ray, computer tomography [CT], or magnetic resonance imaging [MRI]) of at least 1 bone metastasis.

• Female subjects of childbearing potential must have a negative serum or urinepregnancy test within 7 days of first dose of study treatment and agree to useeffective contraception, as defined below, during the study and for 6 months after endof study treatment. Women who report having a pregnancy during this study will befollowed for birth outcomes. GSK acceptable contraceptive methods, when usedconsistently and in accordance with both the product label and the instructions of thephysician, are as follows: An intrauterine device or intrauterine system with adocumented failure rate of less than 1% per year; Male partner sterilization prior tothe female subject's enrollment and the male is the sole sexual partner for thatsubject; the information on the male sterility can come from the site personnel'sreview of subject's medical records; medical examination of the subject and/or semenanalysis; or interview with the subject on his medical history; complete abstinencefrom sexual intercourse for 14 days prior to first dose of study treatment, throughthe dosing period, and for at least 7 months after the last dose of study treatment;double-barrier contraception: male condom combined with a female diaphragm, eitherwith or without a vaginal spermicide (foam, gel, film, cream, or suppository);implants of levonorgestrel or etonogestrel where not contraindicated for this patientpopulation or per local practice; injectable progesterone where not contraindicatedfor this patient population or per local practice; percutaneous contraceptive patcheswhere not contraindicated for this patient population or per local practice; Oralcontraceptives (either combined or progesterone only) where not contraindicated forthis patient population or per local practice. Females of child bearing potential whodo not have male partners as part of their preferred and usual lifestyle are notrequired to use contraception.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (referprotocol for details).

• Adequate baseline organ function as defined by the following criteria: Serum aspartateaminotransferase (AST) <=2.0 x upper limit of normal (ULN); Serum alanineaminotransferase (ALT) <=2.0 x ULN; Serum total bilirubin <=1.0 x ULN; creatinineclearance (calculated using the Cockcroft-Gault formula) >=30 milliliter per minute (mL/min); serum calcium or albumin-adjusted serum calcium >=2.0 millimole per liter (mmol/L) (8.0 mg/dL) and <=2.9 mmol/L (11.5 miligram per deciliter [mg/dL]). Subjectsmust not have taken supplemental calcium for at least 8 hours prior to collection ofthe blood sample for screening serum calcium determination.

• Life expectancy of at least 6 months, in the opinion of the Investigator.

Exclusion Criteria:

• Any serious and/or unstable pre-existing medical, psychiatric disorder, or otherconditions that, in the opinion of the Investigator, could interfere with subject'ssafety, obtaining informed consent or compliance to the study procedures; TheInvestigator should consult the GSK Medical Monitor prior to enrolling a subject ifs/he is unsure if a condition might interfere with the subject's safety orparticipation in this study.

• Any prior treatment with intravenous (IV) or oral bisphosphonates.

• Prior treatment with denosumab.

• Planned radiation therapy or surgery to bone.

• Known brain metastases.

• Prior history or current evidence of osteomyelitis or osteonecrosis of the jaws (ONJ),an active dental or jaw condition that requires oral surgery, non-healed dental ororal surgery, or planned invasive dental procedure over the course of the study.

• Evidence of any of the following conditions per subject self report or medical chartreview: any prior or current malignancy (other than the cancer under study in thisprotocol) with active disease within 3 years before randomization; unstable liverdisease (as defined by the presence of ascites, encephalopathy, coagulopathy,hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), known biliaryabnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones);known infection with human immunodeficiency virus (HIV); active infection withhepatitis B or hepatitis C virus.

• Pregnant women, women planning to become pregnant within 7 months after end of studytreatment, and women who are breastfeeding. Women who are breast feeding shoulddiscontinue nursing prior to the first dose of study treatment and should refrain fromnursing throughout the treatment period and for 7 months following their last dose ofstudy treatment.

• Male subjects unable or unwilling to use adequate contraception methods during thestudy and for 6 months after end of study treatment should be excluded.

• Subject is currently enrolled in another investigational device or investigationalproduct study, or has not completed at least 30 days, 5 half lives, or the duration ofbiological effect, whichever is longer, since ending such a study.

• Known sensitivity to any of the investigational products or supplements to beadministered during the study (i.e., zoledronic acid, mammalian derived products,calcium, or vitamin D).