Sapanisertib in Treating Patients With Stage IV or Recurrent Lung Cancer
Condition: Recurrent Lung Squamous Cell Carcinoma; Stage IV Lung Squamous Cell Carcinoma AJCC v7
MeSH terms: Carcinoma; Carcinoma, Squamous Cell
Intervention: Laboratory Biomarker Analysis; Pharmacological Study; Sapanisertib
Intervention description: Correlative studies; Correlative studies; Given PO
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well sapanisertib works in treating patients with lung cancer
      that is stage IV or has come back (recurrent) and has a mutation in the NFE2L2, KEAP-1, or
      KRAS gene. Damage to these genes may cause the cancer to grow. Sapanisertib may stop this
      from happening by blocking enzymes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed stage IV or recurrent
             squamous cell lung cancer or KRAS mutant lung cancer that harbors any of the NFE2L2
             mutations or KEAP1 mutations; any KEAP1 mutation will be eligible

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded for
             non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) with
             conventional 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 who
             have declined first line therapy or for whom first-line therapy would be clinically
             inappropriate, 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 >= 50
             mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

          -  Patients with controlled diabetes are allowed on study; controlled diabetes is defined
             as 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 this
             reason women of child-bearing potential and men must agree to practice 1 highly
             effective method of contraception and 1 additional effective (barrier) method, at the
             same 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 suspect
             she is pregnant while she or her partner is participating in this study, she should
             inform her treating physician immediately; any woman who becomes pregnant while
             receiving MLN0128 (TAK-228) will be removed from the trial; men treated or enrolled on
             this protocol must also agree to use highly effective barrier contraception prior to
             the study, for the duration of study participation, and 120 days after completion of
             MLN0128 (TAK-228) administration; men must agree not to donate sperm during the course
             of 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 following
             criteria 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 planned
             start of study treatment or those who have not recovered to baseline or less than
             grade 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 treated
             CNS metastases who are off steroids are eligible

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to MLN0128 (TAK-228)

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements; no ischemic myocardial or cerebrovascular event, class III or IV
             heart failure, placement of pacemaker, or pulmonary embolism within six months of
             receiving first dose of MLN0128 (TAK-228)

          -  Baseline prolongation of the rate-corrected QT interval (QTc) > 480 milliseconds, or
             history of congenital long QT syndrome, or torsades de pointes

          -  Pregnant women are excluded from this study because MLN0128 (TAK-228) is an mTOR agent
             with the potential for teratogenic or abortifacient effects; because there is an
             unknown but potential risk for adverse events in nursing infants secondary to
             treatment of the mother with MLN0128 (TAK-228), breastfeeding should be discontinued
             if 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 during
             the study; patients receiving PPI therapy before enrollment must stop using the PPI
             for 7 days before their first dose of study drugs

          -  Uncontrolled diabetes mellitus (fasting plasma glucose > 130 mg/dL despite optimal
             medical management of hyperglycemia)

          -  Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C
             infection

          -  Patients receiving histamine H2 receptor antagonists before enrollment must stop using
             these medications for at least 24 hours before their first dose of study drug