Telotristat Ethyl for the Treatment of Carcinoid Heart Disease in Patients With Metastatic Neuroendocrine Tumor

Inclusion Criteria:

* Patients who are \>= 18 years old will be eligible for the study
* Histopathologically-confirmed,metastatic neuroendocrine tumor and/or locally/regionally advanced neuroendocrine tumor
* Documented history of carcinoid syndrome based on clinical parameters
* Currently receiving stable-dose somatostatin analog (SSA) therapy defined as \>= 2 months

  * Dose of long-acting release (LAR) or depot SSA therapy and on at least:

    * Octreotide LAR at 30 mg every 4 weeks
    * Lanreotide depot at 120 mg every 4 weeks
    * Patients who cannot tolerate SSA therapy at a level indicated above will be allowed to enter at their highest tolerated dose
* Ability and willingness to provide written informed consent
* Patients of childbearing potential must agree to use an adequate method of contraception during the study and for 30 days after the last dose of telotristat ethyl

  * Childbearing potential is defined as those who have not undergone surgical sterilization (eg. documented hysterectomy, tubal ligation, or bilateral salpingo-oophorectomy) or those who are not considered postmenopausal (defined as 12 months of spontaneous amenorrhea).
  * Adequate methods of contraception, defined as having a failure rate of \< 1% per year, for patients or their partner include the following: condom with spermicidal gel, diaphragm with spermicidal gel, intrauterine device, surgical sterilization, vasectomy, oral contraceptive pill, depo-progesterone injections, progesterone implant (ie, Implanon), patch (Ortho Evra), NuvaRing, and abstinence. If a patient is not sexually active but becomes active, he or his partner should use medically accepted forms of contraception
* Eastern Cooperative Oncology Group (ECOG) 0-2

Exclusion Criteria:

* Previous exposure to telotristat ethyl (XERMELO) in the last 3 months
* History of active treatment for malignancy, other than neuroendocrine tumor (malignancies that in the opinion of the Investigator are considered cured, may participate)
* Treatment with any tumor directed therapy, including interferon, chemotherapy, mechanistic target of rapamycin (mTOR) inhibitors \< 4 weeks prior to screening, or hepatic embolization, radiotherapy, peptide receptor radionuclide therapy, and/or tumor debulking \< 12 weeks prior to screening
* History of short bowel syndrome or other known causes of diarrhea unrelated to carcinoid syndrome
* Clinically significant (as per primary investigators judgement) cardiac arrhythmia, bradycardia, tachycardia that would compromise patient safety or the outcome of the study
* Estimated glomerular filtration rate estimated glomerular filtration rate (eGFR) \< 30 ml/min
* Hepatic laboratory values of aspartate transaminase (AST) or alanine aminotransferase (ALT):

  * \> 5 x upper limit of normal (ULN) if patient has documented history of hepatic metastases; or
  * \> 2.5 x ULN if no liver metastases are present
* Pregnant or lactating patients
* Patients receiving everolimus due to poor response to SSA
* Life expectancy \< 6 months
* Any other clinically significant laboratory abnormality that would compromise patient safety or the outcome of the study as per primary investigators judgement
* Any clinically significant and/or uncontrolled cardiac-related abnormality that would compromise patient safety or the outcome of the study including as per primary investigators judgement, but not limited to:

  * Arrhythmia causing hemodynamic compromise
  * Symptomatic severe valvular disease
  * Symptomatic congestive heart failure classified by New York Heart Association (NYHA) class IV
  * Evidence of ischemia on electrocardiography (ECG) with chest pain
  * Unstable angina pectoris
* Current complaints of persistent constipation or history of chronic constipation, bowel obstruction or fecaloma within the past 6 months
* Investigator assessment of known history and/or uncontrolled hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or human immunodeficiency virus (HIV)-1 or HIV-2
* History of substance or alcohol abuse (Diagnostic and Statistical Manual of Mental Disorders 5th edition \[DSM-V\] Criteria for Substance-Related Disorders) within the past 2 years
* History of galactose intolerance, deficiency of Lapp lactase, or glucose-galactose malabsorption
* Receipt of any investigational agent or study treatment (other treatment nor approved by Food and Drug Administration \[FDA\] for carcinoid syndrome or carcinoid heart disease) within the past 30 days
* Existence of any surgical or medical condition that, in the judgment of the Investigator, might compromise patient safety or the outcome of the study
* Presence of any clinically significant findings (relative to the patient population) during review of medical history or upon PE that, in the investigator's opinion, would compromise patient safety or the outcome of the study (e.g., psychiatric illness/social situations that would limit compliance with study requirements)
* Unable or unwilling to communicate or cooperate with the Investigator for any reason