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.

Inclusion Criteria:

• Histologic or cytologic confirmation of lung cancer (squamous, ras-mutated adenocarcinoma or small cell lung cancer)

• Patients must have received at least one course of chemotherapy consisting of a platinum doublet and must have no acceptable standard treatment options

• Prior radiation therapy is permitted as long as:

  • Recovered from the toxic effects of radiation treatment before study entry, except for alopecia

• Absolute neutrophil count (ANC) >= 1500 uL

• Platelets (PLT) >= 100,000 uL

• Hemoglobin (Hgb) >= 9 g/dL

• Total bilirubin =< 1.5 x upper limit of normal (ULN) or direct bilirubin =< ULN

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x ULN or SGOT (AST) and SGPT (ALT) =< 5 x ULN is acceptable if liver has tumor involvement

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2

• Negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential only

• Ability to provide informed consent

• Life expectancy >= 12 weeks

• Willing to return to Mayo Clinic enrolling institution for follow-up

• Willing to provide tissue samples for correlative research purposes

Exclusion Criteria:

• Any of the following:

  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception

• Symptomatic, untreated, or uncontrolled central nervous system (CNS) metastases or seizure disorder; NOTE: patients with treated CNS metastases without evidence of progression and without uncontrolled symptoms or need for steroids may enroll

• Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded

• Unwilling or unable to, comply with the protocol

• Any of the following prior therapies:

  • Radiation to >= 25% of bone marrow
  • Major surgery (i.e., laparotomy), open biopsy, or significant traumatic injury =< 4 weeks prior to registration; minor surgery =< 2 weeks prior to registration; insertion of a vascular access device is not considered major or minor surgery in this regard

• Any of the following concurrent severe and/or uncontrolled medical conditions:

  • Hypertension, labile hypertension, or history of poor compliance with antihypertensive medication
  • Angina pectoris
  • History of congestive heart failure =< 3 months, unless ejection fraction > 40%
  • Myocardial infarction =< 6 months prior to registration
  • Cardiac arrhythmia
  • Poorly controlled diabetes
  • Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
  • Active or recent history of hemoptysis; if hemoptysis has resolved with measures such as palliative radiation therapy (e.g. 3000 cGy over 10 fractions), arteriographic embolization or endobronchial interventions (e.g. photodynamic therapy, brachytherapy), etc. for > 14 days, patients may be considered for participation in this study
  • >= Grade 2 hypertriglyceridemia
  • >= Grade 2 hypercholesterolemia
  • Any illness that in the opinion of the investigator would compromise the ability of the patient to participate safely in the clinical trial

• Use of St. John's Wort because of its effects on hepatic drug metabolism

• Other active malignancy: EXCEPTIONS: Non-melanoma skin cancer, localized prostate cancer, or carcinoma-in-situ of the cervix; NOTE: If there is a history or prior malignancy, patient must not be receiving other cytotoxic or molecularly targeted therapeutics treatment for their cancer; patients receiving certain hormonal manipulations as part of their treatment may be allowed to continue at the discretion of the Principal Investigator (PI) (e.g. luteinizing hormone-releasing hormone [LHRH] analogs for prostate cancer)

• Unable to discontinue use of potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors/inducers