RATIONALE: Inhaling sargramostim may interfere with the growth of tumor cells and may be an effective treatment for melanoma that has spread to the lung.

PURPOSE: This phase I trial is studying the side effects and best dose of inhaled sargramostim in treating patients with melanoma that is metastatic to the lung.

Condition	Treatment or Intervention	Phase
Stage IV Melanoma Recurrent Melanoma lung metastases	Drug: sargramostim  Procedure: biological response modifier therapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: non-specific immune-modulator therapy	Phase I

Further Study Details: 

OBJECTIVES:

• Determine immunomodulatory effects of aerosolized sargramostim (GM-CSF) in patients with metastatic melanoma to the lung.
• Determine toxicity profile of this therapy, in terms of pulmonary and hematologic toxicity, in these patients.
• Determine, preliminarily, the therapeutic effects of this therapy, in terms of progression-free survival, overall survival, and objective response rate, in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive aerosolized sargramostim (GM-CSF) twice a day on days 1-7 and 15-21. Treatment repeats every 28 days for 2 courses. Patients with no disease progression after completion of course 2 may continue on treatment for up to 2 years.

Cohorts of 5-10 patients receive escalating doses of GM-CSF until the optimal immunostimulatory dose (ISD) is determined. The optimal ISD is defined as the dose at which at least 7 of 10 patients experience immunostimulation. Once the optimal ISD is determined, 10 patients receive aerosolized GM-CSF at a dose halfway between the optimal ISD and the preceding dose. Dose escalation is discontinued if at least 2 of 5 or at least 4 of 10 patients on a particular dose level experience dose-limiting toxicity.

Patients are followed at 3 months, every 2 months for 1 year, and then every 4 months for 5 years.

PROJECTED ACCRUAL: A total of 20-55 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic melanoma to the lung for which no known standard therapy exists
• At least 1 unidimensionally measurable lesion
• HLA-A2 positive
• Previously treated CNS metastases allowed provided there is no evidence of disease progression within the past 3 months

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 75,000/mm^3
• Hemoglobin at least 8.0 g/dL

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• AST no greater than 3 times ULN

Renal:

• Creatinine no greater than 2.5 times ULN

Cardiovascular:

• No New York Heart Association class III or IV heart disease

Pulmonary:

• No pulmonary disease requiring concurrent active therapy (e.g., supplemental oxygen or bronchodilator)
• FEV_1 at least 65% of predicted and at least 1.5 L

Immunologic:

• No known immunodeficiency state
• No known autoimmune disease
• No uncontrolled infection

Other:

• No active psychotic disorder requiring pharmacotherapy
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• More than 2 weeks since prior biologic therapy
• More than 2 weeks since prior immunotherapy
• More than 4 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
• No other concurrent biologic therapy or immunotherapy
• No concurrent G-CSF
• No concurrent GM-CSF other than study drug

Chemotherapy:

• More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• No concurrent chemotherapy

Endocrine therapy:

• More than 2 weeks since prior corticosteroids
• No concurrent glucocorticosteroids

Radiotherapy:

• More than 2 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• More than 7 days since prior parenteral antibiotics
• No concurrent parenteral antibiotics
• No concurrent immunosuppressive agents

Study chairs or principal investigators

Svetomir Markovic, MD, PhD,  Study Chair,  Mayo Clinic Cancer Center   

Study ID Numbers:  CDR0000068654; NCCTG-N0071; NCT00017121
Record last reviewed:  March 2005
Last Updated:  March 21, 2005
Record first received:  June 6, 2001
ClinicalTrials.gov Identifier:  NCT00017121
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08