Inhaled Sargramostim in Treating Patients With First Pulmonary (Lung) Recurrence of Osteosarcoma

• Expression of Fas/Fas ligand, presence of dendritic cells, and macrophage infiltration by immunohistochemical analysis before and after the inhalation therapy that follows thoracotomy [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  
• Event free survival at 1, 2, 5, and 10 years after study completion [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  
• Maximum dose utilized in the adult trial is tolerable in pediatric patients after maximum of 40 evaluable patients have been treated at various does levels (e.g., 1000 mcg and 1750 mcg) [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  
• Exploratory/descriptive analysis of histologic findings in resected pulmonary metastases following two courses of therapy and thoracotomy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  

• Patient outcome related to the specific thoracic surgical management based on event free and overall survival at 1, 2, 5, and 10 years after study completion [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Assess the histological findings from patients with first pulmonary recurrence of osteosarcoma who undergo resection of pulmonary metastases after treatment with 2 courses of aerosolized sargramostim (GM-CSF).
• Determine the event-free survival of patients treated with this drug.
• Determine whether the maximum tolerated dose in the trial of inhaled GM-CSF in adult patients with melanoma is tolerable in pediatric patients.

Secondary

• Determine the effect of specific thoracic surgical management on outcome in patients treated with this drug.

OUTLINE: This is a multicenter, dose escalation study. Patients are assigned to 1 of 2 groups according to the extent of pulmonary recurrence (unilateral or bilateral).

• Group I (unilateral recurrence):

  • Initial inhalation therapy: Patients receive inhaled sargramostim (GM-CSF) twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses.
  • Thoracotomy: Patients undergo thoracotomy on day 22.
  • Post-thoracotomy inhalation therapy: Beginning on day 29, or as soon as possible thereafter, patients resume inhalation therapy as above for up to 12 additional courses.

• Group II (bilateral recurrence): Patients may be enrolled on study either before or after the first thoracotomy.

  • First thoracotomy: Patients undergo unilateral thoracotomy.
  • Initial inhalation therapy: Patients receive inhaled GM-CSF, as soon as possible after recovery from first thoracotomy, twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses.
  • Contralateral thoracotomy: Patients undergo contralateral thoracotomy on day 22.
  • Post-thoracotomy inhalation therapy: Beginning on day 29, or as soon as possible, patients resume inhalation therapy as above for up to 12 additional courses.

Treatment in both groups continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 1.6-2 years.