Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	39 and under	NCI	COG-AOST0221 AOST0221, NCT00066365

Objectives

Primary

1. 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).
2. Determine the event-free survival of patients treated with this drug.
3. Determine whether the maximum tolerated dose in the trial of inhaled GM-CSF in adult patients with melanoma is tolerable in pediatric patients.

Secondary

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

Entry Criteria

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

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

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 FEV₁ 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

Expected Enrollment

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

Outcomes

Expression of Fas/Fas ligand, presence of dendritic cells, and macrophage infiltration by immunohistochemical analysis before and after the inhalation therapy that follows thoracotomy
Event free survival at 1, 2, 5, and 10 years after study completion
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)
Exploratory/descriptive analysis of histologic findings in resected pulmonary metastases following two courses of therapy and thoracotomy

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

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.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Carola Arndt, MD, Protocol chair		Ph: 507-284-2511 Email: carndt@mayo.edu

Registry Information
Official Title		A Phase II Study of Aerosolized GM-CSF (NSC# 613795, IND# 11042) in Patients with First Pulmonary Recurrence of Osteosarcoma
Trial Start Date		2004-07-09
Trial Completion Date		2009-04-01 (estimated)
Registered in ClinicalTrials.gov		NCT00066365
Date Submitted to PDQ		2003-06-05
Information Last Verified		2008-10-23
NCI Grant/Contract Number		CA98543

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