This phase I/II trial studies the side effects and best dose of auranofin when given together with sirolimus and to see how well it works in treating patients with lung cancer that has spread or other places in the body and cannot be cured or controlled by treatment or has come back after a period of time during which the cancer could not be detected. Auranofin and sirolimus may stop or slow the growth of lung cancer.
PRIMARY OBJECTIVES: I. To establish the maximum tolerated dose of auranofin plus sirolimus after at least one line of platinum based chemotherapy for lung cancer (squamous, ras-mutated adenocarcinoma, or small cell lung cancer) patients with no acceptable standard treatment options. (Phase I) II. To assess the progression-free survival at four months of patients treated with auranofin after at least one line of platinum based chemotherapy for lung cancer (squamous, ras-mutated adenocarcinoma, or small cell lung cancer) patients with no acceptable standard treatment options. (Phase II) SECONDARY OBJECTIVES: I. To assess the overall survival in this population in comparison to recent historical controls. II. To determine the adverse events (AE) profile and safety of the regimen. III. To determine the overall response rate, per Response Evaluation Criteria In Solid Tumors (RECIST) criteria, and duration of tumor response in those patients with measurable disease. TERTIARY OBJECTIVES: I. To assess the relationship between molecular correlates and progression-free survival (PFS), overall survival (OS), response and adverse events. OUTLINE: This is a phase I, dose-escalation study of auranofin followed by a phase II study. Patients receive auranofin orally (PO) on days 1-28 and sirolimus PO on days 1-28 (days 8-28 of course 1). 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 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
29
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
Mayo Clinic
Jacksonville, Florida, United States
Number of Phase 1 Patients Experiencing a DLT
The number and severity of all adverse events (overall and by dose level) will be tabulated and summarized. A DLT is defined as an adverse event during the first cycle of, at least possibly related to study treatment, and one of the following: Grade 4 Neutropenia, Grade 4 Thrombocytopenia, ≥Grade 3 Anaphylaxis, ≥Grade 3 Proteinuria, ≥Grade 3 Hematuria, ≥Grade 3 Rash acneiform, ≥Grade 3 Diarrhea, ≥Grade 3 Mucositis oral
Time frame: 28 days
Number Phase 1 Patients Experiencing a Grade 3+ AE
Number and severity of all adverse events (overall and by dose level) will be tabulated and summarized.
Time frame: Up to 5 years
Progression-free Survival Rate
A patient is considered to be a 4-month progression-free survivor, or success, if the patient is 4 months from registration without a documentation of disease progression. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated using the properties of the binomial distribution. Additionally, an estimate and confidence interval for the 4-month progression-free survival rate incorporating censoring may be computed using the method of Kaplan-Meier.
Time frame: 4 months
Overall Survival Time
Overall Survival (OS) is defined as the length of time from study enrollment until death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.
Time frame: up to 5 years
Progression-free Survival Time
Progression-free survival is defined as the time from study enrollment until disease progression or death from any cause. The distribution of progression-free survival time will be estimated using the method of Kaplan-Meier.
Time frame: up to 5 years
Number of Patients Achieving a Complete Response (CR) or Partial Response (PR) Noted as the Objective Status
The overall response rate will be estimated in the subset of patients with measurable disease by the number of responses in evaluable patients with measurable disease divided by the total number of evaluable patients with measurable disease.
Time frame: Up to 5 years
Duration of Response
Defined for all evaluable patients with measurable disease who have achieved a response as the date at which the patient's earliest best objective status is first noted to be a CR or PR to the earliest date progression is documented. The distribution of duration of response will be estimated using the method of Kaplan-Meier.
Time frame: Up to 5 years
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