Gemcitabine, Nab-paclitaxel and KPT-330 in Advanced Pancreatic Cancer

Inclusion Criteria:

* Written informed consent in accordance with federal, local, and institutional guidelines
* Patients with metastatic pancreatic adenocarcinoma not treated with chemotherapy for metastatic disease
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* Absolute neutrophil count (ANC) \>= 1500/mm\^3
* Platelet count \>= 100,000/mm\^3
* 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
* Serum creatinine =\< 1.5 mg/dL
* Serum albumin \>= 3.0 g/dL
* Female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and 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
* Patients with history of previously treated malignancies who have no evidence of disease for last five years are allowed to participate

Exclusion Criteria:

* Patients who are pregnant or lactating
* Radiation, chemotherapy, or immunotherapy or any other anticancer therapy =\< 3 weeks prior to cycle 1 day 1; mitomycin C or radio-immunotherapy 6 weeks prior to cycle 1 day 1
* Major surgery within four weeks before cycle 1 day 1
* Unstable cardiovascular function:

  * Symptomatic ischemia, or
  * Uncontrolled clinically significant conduction abnormalities (e.g.: ventricular tachycardia on antiarrhythmics are excluded and 1st degree atrioventricular \[AV\] block or asymptomatic left anterior fascicular block \[LAFB\]/right bundle branch block \[RBBB\] will not be excluded), or
  * Congestive heart failure (CHF) of New York Heart Association (NYHA) class \>= 3, or
  * Myocardial infarction (MI) within 3 months of cycle 1 day 1 dose
* Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose
* Known to be HIV seropositive who are on anti-HIV drugs because of the unknown interactions between these drugs and the study agents
* Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus (HCV) ribonucleic acid (RNA) or HBsAg (hepatitis B virus \[HBV\] surface antigen)
* Patients with active central nervous system (CNS) malignancy; asymptomatic small lesions are not considered active; treated lesions may be considered inactive if they are stable for at least 3 months
* Patients with significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea
* Grade \>= 2 peripheral neuropathy within 14 days prior to cycle 1 day 1
* History of seizures, movement disorders or cerebrovascular accident within the past 5 years prior to cycle 1 day 1
* Patients with muscular degeneration, uncontrolled glaucoma, or markedly decreased visual acuity based on physician's assessment
* Serious psychiatric or medical conditions that could interfere with treatment
* Participation in an investigational anti-cancer study within 3 weeks prior to cycle 1 day 1
* Concurrent therapy with approved or investigational anticancer therapeutic
* Presence of clinically significant ascites