Inhaled Sargramostim in Treating Patients With Melanoma Metastatic to the Lung

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 1

Conditions: Metastatic Cancer; Melanoma (Skin)

Treatments: Biological: sargramostim

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00017121

NCI-2012-02385 (Registry Identifier)

CDR0000068654 (Registry Identifier)

NCCTG-N0071

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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40 participants in 1 patient group

sargramostim

Experimental group

Description:

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.

Treatment:

Biological: sargramostim