A Study of Bevacizumab in Combination With Chemotherapy for Treatment of Osteosarcoma

This is a comprehensive study that uses a novel agent that targets angiogenesis (bevacizumab)
in combination with conventional chemotherapy for the treatment of osteosarcoma. Bevacizumab,
a monoclonal antibody against the vascular endothelial growth factor (VEGF), has been shown
to stop the growth of new blood vessels of tumors, both in the laboratory and in patients
with other types of cancers. Bevacizumab has improved the effect of chemotherapy in adult
patients with different types of cancer by increasing tumor response and increasing the
chances of survival. This study has two main goals:

- To find out if bevacizumab can be combined safely with chemotherapy for osteosarcoma

- To find out if adding bevacizumab to chemotherapy will be beneficial in treating
osteosarcoma.

The chemotherapy drugs used in this study are commonly used to treat osteosarcoma. Patients
with non-metastatic and resectable tumors receive bevacizumab and chemotherapy comprised of
cisplatin, doxorubicin and high-dose methotrexate. Patients with metastatic tumors or tumors
that cannot be removed by surgery receive bevacizumab and chemotherapy comprised of
cisplatin, doxorubicin and high-dose methotrexate, ifosfamide and etoposide. If the tumor can
be removed by surgery, surgery will be performed after 10 weeks of chemotherapy and will be
followed by additional chemotherapy. After completion of active therapy, patient's response
to therapy will be followed for approximately 5 years.

Inclusion Criteria:

- Patient must have newly diagnosed high-grade, biopsy proven, osteosarcoma or malignant
fibrous histiocytoma (MFH) of bone with no history of prior chemotherapy or radiation;

- Participant is able to perform tasks and daily activities as defined in the study
guidelines

- Patient meets established guidelines for adequate function of the kidney, liver, heart
and bone marrow

- Participants meets other requirements defined in the eligibility portion of the study

Exclusion Criteria:

- recent major surgical procedure or injury

- Known bleeding diathesis, platelet disorder or coagulopathy

- Thrombosis

- Cardiac disease or hypertension

- Significant proteinuria

- Central nervous system disease

- Gastrointestinal perforation/abdominal fistula

- Osteosarcoma or MFH of bone as second malignancy