This phase II trial tests the safety, best dose, and effectiveness of inhaled aerosolized sargramostim in combination with standard immunotherapy (nivolumab) for the treatment of patients with melanoma that has spread from where it first started (primary site) to the lung (metastatic to the lung). Sargramostim works to stimulate the immune system by prompting the bone marrow to produce more white blood cells. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. In this study, an aerosolized form of sargramostim is inhaled using a device called a nebulizer, which can deliver the drug directly to the lungs. Inhalation of aerosolized sargramostim in combination with nivolumab may be more effective at treating patients melanoma metastatic to the lung.
PRIMARY OBJECTIVE: I. To determine feasibility, safety (maximum tolerated dose, MTD), and/or the maximally immunologically effective dose of aerosolized sargramostim (aSAR) administered as an inhalation in combination with nivolumab for the treatment of patients with metastatic malignant melanoma with evidence of pulmonary metastases. SECONDARY OBJECTIVES: I. To assess the pharmacodynamics of inhaled aSAR administered in combination with nivolumab for the treatment of metastatic malignant melanoma. II. To gather preliminary data on the clinical efficacy of aSAR + nivolumab therapy as 2nd line treatment for patients with metastatic melanoma. OUTLINE: This is a dose escalation study of aerosolized sargramostim. Patients receive aerosolized sargramostim via inhalation using the Aerogen Solo nebulization device and receive nivolumab intravenously (IV) on study. Patients also undergo collection of blood samples on study and undergo computed tomography (CT) or magnetic resonance imaging (MRI) at screening and on study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Given via inhalation with nebulizer
Undergo collection of blood samples
Undergo CT
Undergo MRI
Use Aerogen Solo nebulization device
Given IV
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Maximum tolerated dose (MTD)
The MRD is the dose level where at most 1 of the 6 patients treated at that dose level develops a dose-limiting event during the first cycle of treatment.
Time frame: During the first cycle of treatment (each Cycle = 28 ±3 days)
Incidence of adverse events
Adverse events will be identified using Common Terminology Criteria for Adverse Events version 5.0. The maximum grade of each type of adverse event will be recorded for each patient. For each adverse event reported by dose level, the percentage of patients developing any degree of that adverse event as well as the percentage of patients developing a severe degree (grade 3 or higher) will be determined.
Time frame: Up to 30 days after last treatment
Progression-free survival (PFS)
PFS distribution will be estimated using the Kaplan-Meier method.
Time frame: Time from study entry to the documentation of disease progression, assessed up to 2 years after registration
Overall survival (OS)
OS distribution will be estimated using the Kaplan-Meier method.
Time frame: Time from study entry to death, assessed up to 2 years after registration
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.