Selinexor in Treating Patients With Relapsed Small Cell Lung Cancer

Inclusion Criteria:

* Written informed consent in accordance with federal, local, and institutional guidelines
* Patients should have estimated life expectancy of \> 3 months at study entry
* Patients with relapsed small cell lung cancer - diagnosis must be histologically confirmed
* Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at the time of study entry
* Objective evidence of disease progression on study entry
* Prior systemic anticancer therapy: patients will have received no more than 2 prior chemotherapy regimens; the regimen(s) may have included biological, molecularly targeted or immune therapies; patients with primary refractory disease (i.e., those patients with progressive disease on first line chemotherapy) and patients with disease relapse within 90 days of completion of initial chemotherapy (chemotherapy resistant) are excluded; patients with limited stage small cell lung cancer (SCLC) and systemic relapse who are not felt to be candidates for repeat platinum-based chemotherapy at relapse are eligible for enrollment
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* Absolute neutrophil count (ANC) \> 1000/mm\^3
* Platelet count \> 75,000 mm\^3
* Total bilirubin \< 2 times the upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of \< 3 times ULN)
* Alanine aminotransferase (ALT) \< 2.5 times ULN; in the case of known (radiological and/or biopsy documented) liver metastasis, ALT \< 5.0 times ULN is acceptable
* Albumin \>= 3.0 mg/dl
* Estimated creatinine clearance of \>= 30 mL/min, calculated using the formula of Cockroft and Gault
* Amylase =\< 1.5 x ULN
* Lipase =\< 1.5 x ULN
* Alkaline phosphatase limit =\< 2.5 x ULN
* Female patients of childbearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening; male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential; acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal; for both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose
* Resolution to grade =\< 1 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v4.03) of all clinically significant toxic effects of prior anti-cancer therapy (with the exception neuropathy, which may be =\< grade 2 within 14 days prior to cycle 1 day 1)
* Available archival tumor tissue or willingness to undergo repeat biopsy is required at trial initiation

Exclusion Criteria:

* Primary refractory disease (progressive disease on initial platinum based chemotherapy) or chemotherapy-resistant disease (disease progression within 90 days of completion of initial chemotherapy)
* Patients who are pregnant or lactating
* Radiation, chemotherapy, or immunotherapy or any other anticancer therapy =\< 2 weeks prior to cycle 1 day 1; any clinical trial therapy (including investigational anti-cancer study) =\< 3 weeks prior to cycle 1 day 1
* Prior treatment with selinexor
* Major surgery within 3 weeks before day 1
* Unstable cardiovascular function:

  * Electrocardiogram (ECG) abnormalities requiring treatment, or
  * Congestive heart failure (CHF) of New York Heart Association (NYHA) class \>= 3
  * Myocardial infarction (MI) within 3 months
  * Symptomatic ischemia or angina
* Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; patients with controlled infection or on prophylactic antibiotics are permitted in the study
* Known to be human immunodeficiency virus (HIV) seropositive
* Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus (HCV) RNA or hepatitis B surface antigen (HBsAg) (hepatitis B virus \[HBV\] surface antigen)
* Serious psychiatric or medical conditions that could interfere with treatment
* History of seizures, movement disorders or cerebrovascular accident within the past 5 years prior to cycle 1 day 1
* Concurrent therapy with approved or investigational anticancer therapeutic other than steroids
* Patients with \> 3 liver metastases at time of enrollment
* Patients with coagulation problems and active bleeding in the last month (peptic ulcer, epistaxis, spontaneous bleeding)
* Patients with significantly diseased or obstructed gastrointestinal tract, malabsorption, uncontrolled vomiting or diarrhea or inability to swallow oral medications
* Patients who are severely underweight (body mass index \[BMI\] less than 17) or patients with a body surface area (BSA) \< 1.4 m\^2 as calculated per Dubois 1916 or Mosteller 1987
* Uncontrolled brain metastases or leptomeningeal involvement; patients with brain metastases are permitted if they have received appropriate therapy and demonstrated control of the brain metastases or leptomeningeal disease following therapy; patients with known brain metastases will require magnetic resonance imaging (MRI) brain to demonstrate disease control prior to enrollment (lack of symptom progression for two weeks off therapeutic doses of steroids, excluding chronic steroids used for control of chronic obstructive pulmonary disease \[COPD\])
* Prior cancer diagnosis is allowed if patient is disease-free for \>= 3 years, or disease free for \< 3 years for treated basal cell/ squamous cell skin cancer or in situ cervical cancer