Inhaled Sargramostim in Treating Patients With Melanoma Metastatic to the Lung

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.

OBJECTIVES:

* Determine immunomodulatory effects of aerosolized sargramostim (GM-CSF) in patients with metastatic melanoma to the lung (part A).
* 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.
* Determine the maximum tolerated dose of GM-CSF in these patients (part B).

OUTLINE: This is a dose-escalation, multicenter 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 until disease progression. Patients are grouped to 1 of 2 dose-escalation regimens (part A vs B).

* Part A: 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.
* Part B: Cohorts of 3-6 patients receive escalating doses of GM-CSF until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

After completion of study therapy, patients are followed at 3 months, every 2 months for 1 year, and then every 3-4 months for 5 years.

PROJECTED ACCRUAL: A total of 85 patients will be accrued for this study.

Eligibility 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 (part A patients only)
* 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