Patient case: 11-year-old male with Peutz-Jeghers syndrome; genetic feature: STK11

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

Summary: RATIONALE: Inhaling aerosolized sargramostim before and after surgery may interfere with the growth of tumor cells and shrink the tumor so that it can be removed during surgery. Sargramostim may then kill any tumor cells remaining after surgery. This may be an effective treatment for osteosarcoma that has spread to the lung.
  PURPOSE: This phase II trial is studying how well inhaled sargramostim works in treating patients who are undergoing surgery for the first recurrence of osteosarcoma that has spread to the lung.

Detailed description: 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.

Eligibility: DISEASE CHARACTERISTICS:
  -  Histologically confirmed osteosarcoma at primary diagnosis
  -  Lesions detected in at least 1 lung that are consistent with metastatic disease and approachable with thoracotomy
  -  No prior recurrence of osteosarcoma
  -  No other sites of metastases
  -  Resectable pulmonary nodule(s), defined as nodule(s) that are removable without performing a pneumonectomy (e.g., nodules immediately adjacent to the main stem bronchus or main pulmonary vessels)
  -  Prior thoracotomy allowed in patients with imaging consistent with metastatic involvement in both lungs provided the lung on which the thoracotomy was performed is disease-free
  -  No pleural effusion or pleural based nodules
  PATIENT CHARACTERISTICS:
  Age
  -  39 and under
  Performance status
  -  Karnofsky 50-100% (patients over 16 years of age)
  -  Lansky 50-100% (patients 16 years of age and under)
  Life expectancy
  -  At least 8 weeks
  Hematopoietic
  -  Not specified
  Hepatic
  -  Not specified
  Renal
  -  Not specified
  Pulmonary
  -  No evidence of dyspnea at rest
  -  No exercise intolerance
  -  Pulse oximetry at least 94%
  -  Baseline Forced expiratory volume in 1 second (FEV_1) at least 80% of predicted
  -  No history of asthma
  -  No history of reactive airway disease
  -  No history of bronchospasm
  Other
  -  Willing and able to perform inhalation therapy
  -  No medical contraindication to surgical excision
  -  Not pregnant or nursing
  -  Negative pregnancy test
  -  Fertile patients must use effective contraception
  PRIOR CONCURRENT THERAPY:
  Biologic therapy
  -  No other concurrent immunotherapy
  -  No other concurrent immunomodulating agents
  Chemotherapy
  -  No concurrent anticancer chemotherapy
  Endocrine therapy
  -  No concurrent steroids by any route
  Radiotherapy
  -  Not specified
  Surgery
  -  See Disease Characteristics
  -  No concurrent thoracoscopy or video-assisted thoracic surgery
  Other
  -  No more than 1 prior treatment regimen for osteosarcoma
  -  No concurrent participation in another COG therapeutic study

Relevance to patient case: not relevant