This phase I clinical trial studies the side effects and best dose of auranofin and sirolimus when given together in treating patients with non-small cell lung cancer. Immunosuppressive therapy, such as auranofin and sirolimus, may be an effective treatment for non-small cell lung cancer. Sirolimus may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving auranofin and sirolimus may be an effective treatment for non-small cell lung cancer.
PRIMARY OBJECTIVES: I. To determine the maximally tolerated dose (MTD) of auranofin plus sirolimus (Cohort I). II. To determine the confirmed response rate of auranofin plus sirolimus (Cohort II). SECONDARY OBJECTIVES: I. To describe the adverse event and toxicity profiles associated with this treatment combination. II. To evaluate response, time to progression, progression-free survival (PFS), overall survival (OS), and time to treatment failure in patients treated with this treatment combination. TERTIARY OBJECTIVES: I. To evaluate tumor biomarkers of protein kinase C (PKC) and mammalian target of rapamycin (mTOR) signaling activity as predictors of clinical outcome (i.e. response, PFS, OS) for patients receiving auranofin/sirolimus therapy. II. To evaluate the use of surrogate biomarkers of PKC and mTOR inhibition in peripheral blood lymphocytes (PBLs) as predictors of clinical outcome (i.e. response, PFS, OS) for patients receiving auranofin/sirolimus therapy. OUTLINE: This is a cohort I, dose-escalation study followed by a cohort II study. Patients receive auranofin orally (PO) once daily (QD) and sirolimus PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3-6 months for 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Mayo Clinic in Florida
Jacksonville, Florida, United States
MTD defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Cohort I)
Time frame: 28 days
Proportion of confirmed tumor responses assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Cohort II)
Will be estimated by the number of confirmed responses divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
Time frame: Up to 24 weeks
Incidence of adverse events assessed using NCI CTCAE version 4.0
The number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized. The grade 3+ adverse events will also be described and summarized in a similar fashion.
Time frame: Up to 2 years
Overall toxicity incidence evaluated using the Common Toxicity Criteria (CTC) standard toxicity grading
Overall toxicity incidence as well as toxicity profiles by dose level, patient, and tumor site will be explored and summarized. Frequency distributions, graphical techniques, and other descriptive measures will form the basis of these analyses.
Time frame: Up to 2 years
Confirmed and best responses
Will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall, by tumor group, and by cohort).
Time frame: Up to 2 years
Time to progression
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Correlative studies
Will be summarized descriptively using Kaplan Meier methodology, the log-rank test, and Cox Proportional Hazards models (where appropriate given the small sample size).
Time frame: Up to 2 years
PFS
Will be summarized descriptively using Kaplan Meier methodology, the log-rank test, and Cox Proportional Hazards models (where appropriate given the small sample size).
Time frame: Up to 2 years
OS
Will be summarized descriptively using Kaplan Meier methodology, the log-rank test, and Cox Proportional Hazards models (where appropriate given the small sample size).
Time frame: Up to 2 years
Time to treatment failure
Will be summarized descriptively using Kaplan Meier methodology, the log-rank test, and Cox Proportional Hazards models (where appropriate given the small sample size).
Time frame: From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 2 years