Phase I Dose Escalation of Monthly Intravenous Ra-223 Dichloride in Osteosarcoma

Inclusion Criteria:

1. Patients with progressive, locally recurrent, or metastatic osteosarcoma (i.e. high-risk only) with no standard curative options available with at least one indicator lesion avid on 99mTc-MDP scan or a Sodium Fluoride (Na F) Bone PET scan will be eligible. In addition, subjects with extremely rare bone forming osteosarcoma-like tumors that behave like osteosarcoma phenotypically and are clinically treated like osteosarcoma (eg. Malignant Fibrous Histiocytoma of Bone or malignant transformation of giant cell tumor of bone) may be included if they satisfy all of the inclusion criteria.
2. Anatomic imaging (CT or MRI) of all sites of disease along with chest CT at baseline and restaging for all patients will be done to allow for assessment of RECIST progression. RECIST progression will determine progressive disease regardless of other imaging.
3. Indicator lesion that has uptake of 99mTc-MDP on bone scan or a Sodium Fluoride ( Na F) Bone PET scan and can be subjected to quantitative assessment by this scans and possibly other means.
4. Age 15 and above and \>40 kg.
5. ECOG=2 or better
6. Subjects or their guardians must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.
7. All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v4.0 Grade 1 or less at the time of signing the Informed Consent Form (ICF).
8. Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to the start of study drug. Post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test.
9. Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF until at least 30 days after the last dose of study drug. The definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate.
10. Acceptable hematology and serum biochemistry screening values: White Blood Cell Count (WBC) \>= 1500/mm3; Absolute Neutrophil Count (ANC) \>= 1,000/mm3; Platelet (PLT) count \>= 75,000/mm3; Hemoglobin (HGB) \>= 8 g/dl; Total bilirubin level \<= 1.5 x institutional upper limit of normal (ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<= 2.5 x ULN; Creatinine \<= 1.5 x ULN; Albumin \> 25 g/L
11. Willing and able to comply with the protocol, including follow-up visits and examinations.
12. Patients with progressive, locally recurrent, or metastatic osteosarcoma (i.e. high-risk only) with at least one indicator lesion avid on 99mTc-MDP scan will be eligible.

Exclusion Criteria:

1. Diagnosis other than osteosarcoma.
2. 99mTc-MDP bone scan with no significant uptake (i.e. "nothing" for a bone-seeking isotope to target/ i.e. indicator lesion that would be expected to have the bone-seeking targeted uptake of 223-radium dichloride).
3. Other malignancy treated within the last 3 years (except non-melanoma skin cancer or low-grade superficial bladder cancer).
4. Any other serious illness or medical condition, such as but not limited to: Any active infection \>= National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 Grade 2; Cardiac failure New York Heart Association (NYHA) III or IV; Fecal incontinence (this is because of Ra-223 elimination in feces).
5. Women who are pregnant or breast-feeding.
6. Inability to comply with the protocol and/or not willing or not available for follow-up assessments.
7. Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.
8. Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization)
9. Patients on oxygen