Melanoma (Skin), Metastatic Cancer
Conditions
Keywords
stage IV melanoma, recurrent melanoma, lung metastases
Brief 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.
Detailed description
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.
Interventions
BIOLOGICALsargramostim
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival | Up to 6 years |
Secondary
| Measure | Time frame |
|---|---|
| Progression-free survival | Up to 6 years |
| Overall survival | Up to 6 years |
| Objective response rate | Up to 6 years |
Countries
United States
Outcome results
None listed