This phase I/II trial studies the side effects and best dose of aerosolized aldesleukin and to see how well it works in treating patients with cancer that has spread from the original tumor to the lungs. Biological therapies, such as aerosolized aldesleukin, may stimulate or suppress the immune system in different ways and stop tumor cells from growing.
PRIMARY OBJECTIVES: I. To evaluate toxicity in patients with lung metastases during aerosol interleukin (IL)-2 (aldesleukin) therapy using self-report, remote spirometry and pulse oximetry. SECONDARY OBJECTIVES: I. To determine dose and schedule of an acceptable aerosol IL-2 regimen and correlate with absolute lymphocyte count (ALC). II. To determine serum IL-2 levels on day 1 of therapy for evidence of spillover into circulation and correlate with absence or presence of toxicity. III. To evaluate the efficacy of aerosol IL-2 treatment using Response Evaluation Criteria in Solid Tumors (RECIST). TERTIARY OBJECTIVES: I. To evaluate the histology in post-surgical specimens in patients who undergo surgery for lung metastases following aerosol IL-2 treatment as an optional procedure. II. To evaluate immune correlates from optional pre-treatment biopsy and post-surgical specimen. OUTLINE: This is a phase I, dose-escalation study followed by a phase II study. Patients receive aerosolized aldesleukin once daily (QD) on days 1-21. Courses repeat every 28 days in the absence of disease progression of unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
70
Breathe aerosolized aldesleukin
Optional correlative studies
M D Anderson Cancer Center
Houston, Texas, United States
Maximum tolerated dose, defined as the highest dose level with six patients with at most one dose limiting toxicity, using the CTCAE v4.0 (Phase I)
The dose escalation will be conducted via the accelerated titration method for the first 2 dose levels.
Time frame: 28 days
Incidence of adverse events (AE)s, using the CTCAE v4.0 (Phase II)
AEs will be summarized by severity according to the worst grade experienced over the number of patients at risk.
Time frame: Up to 4 years
Response of measurable lesions to aerosol aldesleukin using modified RECIST (Phase II)
Response analysis will be performed on intent-to-treat, that is, any patient who enrolled into the expansion cohort. Patients who withdraw before the end of 2 months without responding will be considered non-responders. The two-sided 95% Clopper-Pearson confidence intervals will be calculated for the proportion of patients with responses.
Time frame: Up to 4 years
IL-2 levels in serum
Serum IL-2 levels will be compared with maximum grade of toxicity to determine whether our hypothesis of "spillover" of IL-2 in the circulation - i.e. some escaping the receptor gauntlet of IL-2 receptor bearing cells in pulmonary lymphatics.
Time frame: Day 1 of therapy
Changes in biomarker levels
Changes in biomarker levels between pre- and post-treatment tissue samples will be assessed using paired t-tests (if the data are normally distributed) or Wilcoxon signed-rank tests (otherwise). Will graph the data using histograms, box plots and dot plots. With 20 patients, using a 2-sided 5% alpha, there would be 80% power to detect an effect size of 0.66 (where the effect size is the mean difference divided by the standard deviation of the differences).
Time frame: Baseline to 8 weeks
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