Trial Information

A Phase II Study of Chemotherapy and Pamidronate for the Treatment of Newly Diagnosed Osteosarcoma

OBJECTIVES:

- Determine the safety and feasibility of pamidronate with standard induction and
maintenance chemotherapy in patients with newly diagnosed high-grade osteosarcoma.

- Determine the frequency of favorable tumor necrosis produced in patients treated with
this regimen.

- Determine the event-free survival of patients without metastatic disease at
presentation treated with this regimen.

- Determine the prosthesis failure-free survival of patients treated with this regimen
and who ultimately undergo limb preservation surgery with insertion of an
endoprosthesis.

OUTLINE: Patients are stratified according to extent of disease (localized vs metastatic).

- Induction therapy: Patients receive standard chemotherapy comprising cisplatin IV over
4 hours and doxorubicin IV over 15-30 minutes on weeks 0 and 5 and high-dose
methotrexate IV over 4 hours on weeks 3, 4, 8, and 9. Patients also receive pamidronate
IV over 2-4 hours beginning approximately 3 days after initiation of chemotherapy on
week 0 and repeating once every 4 weeks. Treatment continues in the absence of disease
progression or unacceptable toxicity.

- Surgery*: Patients undergo surgical resection of primary tumor on week 10 and then
proceed to maintenance therapy. Patients with metastatic disease undergo further
surgery of metastatic sites after recovery from definitive resection of the primary
tumor before proceeding to maintenance therapy.

NOTE: *Patients who have undergone definitive surgical resection before study entry may
proceed to maintenance therapy or, if appropriate, surgical resection of metastatic disease

- Maintenance therapy: Patients receive standard chemotherapy comprising cisplatin IV
over 4 hours on weeks 0 and 5; doxorubicin IV over 15-30 minutes on weeks 0, 5, 10, and
15; and high-dose methotrexate IV over 4 hours on weeks 3, 4, 8, 9, 13, 14, 18, and 19.
Patients also receive pamidronate as in induction therapy for up to 1 year. Treatment
continues in the absence of disease progression or unacceptable toxicity.

Patients are followed monthly for 1 year.

PROJECTED ACCRUAL: A total of 75 patients (50 with localized disease; 25 with metastatic
disease) will be accrued for this study within 3-4 years.