inhaled sargramostim in treating patients with melanoma metastatic to the lung

Conditions: Melanoma (Skin); Metastatic Cancer

Summary: 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

Keywords: stage iv melanoma recurrent melanoma lung metastases