Denosumab in Treating Patients With Recurrent or Refractory Osteosarcoma

Inclusion Criteria:

   - Female patients must have a bone age of equal to or greater than 12 years of age as
   determined by local read of appropriate radiographic imaging

   - Male patients must have a bone age of equal to or greater than 14 years of age as
   determined by local read of appropriate radiographic imaging

   - Patients must have relapsed or become refractory to conventional therapy, with a
   regimen including some combination of high dose methotrexate, doxorubicin, cisplatin,
   ifosfamide and etoposide; and have had histologic verification of osteosarcoma at
   original diagnosis or at the time of recurrence

   - Cohort 1 patients must have measurable disease according to Response Evaluation
   Criteria in Solid Tumors (RECIST) 1.1

   - Cohort 2 patients must have had a complete resection of all sites of metastatic
   disease within 30 days prior to enrollment

      - Patients will only be eligible after they have undergone complete surgical
      resection of suspected metastatic disease that is histopathologically confirmed
      to be osteosarcoma prior to enrollment

         - Note: the definition of complete resections is: gross resection of all
         disease as per the operating surgeon; post-operative imaging is not required
         for confirmation of complete resection

      - Patients must undergo resection of any lung lesion meeting criteria for likely
      metastatic disease, defined as:

         - 3 or more lesions > 5 mm in diameter OR a single lesion > 1 cm

      - Patients with lung as the only site of resected metastatic disease must have
      refused participation in protocol AOST1421

         - Note: This applies if AOST1421 is open to enrollment at the enrolling
         institution on the day the patient consents

   - Patient must have adequate tumor specimen available for submission

   - Patients must have a performance status corresponding to Eastern Cooperative Oncology
   Group (ECOG) scores of 0, 1 or 2; use Karnofsky for patients > 16 years of age and
   Lansky for patients =< 16 years of age

   - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
   mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

      - Age: 11 to < 13 years old; 1.2 (male, female) maximum serum creatinine (mg/dL)

      - Age: 13 to < 16 years old; 1.5 (male), 1.4 (female) maximum serum creatinine
      (mg/dL)

      - Age: >= 16 years old; 1.7 (male), 1.4 (female) maximum serum creatinine (mg/dL)

   - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age

   - Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
   serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x
   ULN for age

   - Serum calcium or albumin-adjusted serum calcium >= 2.0 mmol/L (8.0 mg/dL) and =< 2.9
   mmol/L (11.5 mg/dL)

Exclusion Criteria:

   - Patients with known sensitivity to any of the products to be administered during the
   study (eg, mammalian derived products, calcium or vitamin D)

   - Patients who are receiving other cancer directed therapy at the time of enrollment

   - Patients who have previously received denosumab

   - Patients who have previously received mithramycin, strontium-89, samarium-153 or
   rhenium

   - Patients receiving bisphosphonates

   - Pre-existing conditions

      - Disorders associated with abnormal bone metabolism

      - Hypocalcemia that is not corrected with oral calcium supplementation

      - Vitamin D < 20 mg/mL

      - Paget's disease

      - Prior history or current evidence of osteonecrosis of the jaw

      - Any dental or oral condition likely to result in disruption of mucosal integrity
      during denosumab therapy including: active dental or jaw condition requiring oral
      surgery or tooth extraction; non-healed dental or oral surgery or planned
      invasive dental procedures during the anticipated course of study therapy

      - Unstable systemic disease, excluding osteosarcoma, such as unstable proximal
      renal tubule dysfunction (Fanconi syndrome) or congestive heart failure

   - Pregnancy and breast feeding

      - Female patients who are pregnant; a pregnancy test is required for female
      patients of childbearing potential

      - Lactating females who plan to breastfeed their infants while on study therapy and
      through 5 months after completion of study therapy

      - Sexually active patients of reproductive potential who have not agreed to use an
      effective contraceptive method for the duration of their study participation and
      for 5 months after the end of study treatment

   - All patients and/or their parents or legal guardians must sign a written informed
   consent

   - All institutional, Food and Drug Administration (FDA), and National Cancer Institute
   (NCI) requirements for human studies must be met