Sapanisertib in Treating Patients With Stage IV or Recurrent Lung Cancer

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed stage IV or recurrentsquamous cell lung cancer or KRAS mutant lung cancer that harbors any of the NFE2L2mutations or KEAP1 mutations; any KEAP1 mutation will be eligible
• Patients must have measurable disease, defined as at least one lesion that can beaccurately measured in at least one dimension (longest diameter to be recorded fornon-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) withconventional techniques or as >= 10 mm (>= 1 cm) with spiral computed tomography (CT)scan, magnetic resonance imaging (MRI), or calipers by clinical exam
• Patients must have completed at least 1 prior line of systemic therapy; patients whohave declined first line therapy or for whom first-line therapy would be clinicallyinappropriate, will be considered eligible for the trial
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Life expectancy of greater than 3 months
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin within normal institutional limits
• Fasting serum glucose =< 130 mg/dL or hemoglobin A1C (HBA1C) < 7.0%
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
• Creatinine within normal institutional limits OR creatinine clearance >= 50mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Patients with controlled diabetes are allowed on study; controlled diabetes is definedas fetal bovine serum (FBS) =< 130 mg/dL in the context of this study
• The effects of MLN0128 (TAK-228) on the developing human fetus are unknown; for thisreason women of child-bearing potential and men must agree to practice 1 highlyeffective method of contraception and 1 additional effective (barrier) method, at thesame time, prior to study through 90 days (or longer, as mandated by local labeling [e.g., United States Package Insert (USPI), Summary of Product Characteristics (SmPC),etc;]) after the last dose of study drug; should a woman become pregnant or suspectshe is pregnant while she or her partner is participating in this study, she shouldinform her treating physician immediately; any woman who becomes pregnant whilereceiving MLN0128 (TAK-228) will be removed from the trial; men treated or enrolled onthis protocol must also agree to use highly effective barrier contraception prior tothe study, for the duration of study participation, and 120 days after completion ofMLN0128 (TAK-228) administration; men must agree not to donate sperm during the courseof this study or within 120 days after receiving their last dose of study drug
• Ability to understand and the willingness to sign a written informed consent document
• Ability to swallow oral medications
• Known human immunodeficiency virus (HIV) positive patients who meet the followingcriteria will be considered eligible:
• CD4 count > 350 cells/mm^3
• Undetectable viral load
• Maintained on modern therapeutic regimens utilizing non-CYP-interactive agents

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 2 weeks prior to the plannedstart of study treatment or those who have not recovered to baseline or less thangrade 2 from adverse events from prior treatments
• Patients who are receiving any other investigational agents
• Patients with untreated central nervous system (CNS) metastases; patients with treatedCNS metastases who are off steroids are eligible
• History of allergic reactions attributed to compounds of similar chemical or biologiccomposition to MLN0128 (TAK-228)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliance withstudy requirements; no ischemic myocardial or cerebrovascular event, class III or IVheart failure, placement of pacemaker, or pulmonary embolism within six months ofreceiving first dose of MLN0128 (TAK-228)
• Baseline prolongation of the rate-corrected QT interval (QTc) > 480 milliseconds, orhistory of congenital long QT syndrome, or torsades de pointes
• Pregnant women are excluded from this study because MLN0128 (TAK-228) is an mTOR agentwith the potential for teratogenic or abortifacient effects; because there is anunknown but potential risk for adverse events in nursing infants secondary totreatment of the mother with MLN0128 (TAK-228), breastfeeding should be discontinuedif the mother is treated with MLN0128 (TAK-228)
• Patients previously treated with an mammalian TOR (mTOR) or PI3K inhibitor
• Concomitant administration of any proton pump inhibitor (PPI) is not permitted duringthe study; patients receiving PPI therapy before enrollment must stop using the PPIfor 7 days before their first dose of study drugs
• Uncontrolled diabetes mellitus (fasting plasma glucose > 130 mg/dL despite optimalmedical management of hyperglycemia)
• Known hepatitis B surface antigen-positive, or known or suspected active hepatitis Cinfection
• Patients receiving histamine H2 receptor antagonists before enrollment must stop usingthese medications for at least 24 hours before their first dose of study drug