Inhaled Sargramostim in Treating Patients With Melanoma Metastatic to the Lung

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Dose Finding Study of Aerosolized GM-CSF in the Treatment of Metastatic Melanoma to the Lung

Conditions
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Melanoma (Skin), Metastatic Cancer

Intervention / Treatment
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* Biological: sargramostim


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sargramostim<br>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). 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. | Biological: sargramostim<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | Up to 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | Up to 6 years | 
| Overall survival |  | Up to 6 years | 
| Objective response rate |  | Up to 6 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV melanoma, recurrent melanoma, lung metastases