Abemaciclib in Treating Patients With Advanced, Refractory, and Unresectable Digestive System Neuroendocrine Tumors
Abemaciclib in Treating Patients With Advanced, Refractory, and Unresectable Digestive System Neuroendocrine Tumors
This phase II trial studies how well abemaciclib works in treating patients with digestive
 system neuroendocrine tumors that have spread to other places in the body, do not respond to
 treatment, and cannot be removed by surgery. Abemaciclib may stop the growth of tumor cells
 by blocking some of the enzymes needed for cell growth.
Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every
 28 days in the absence of disease progression or unacceptable toxicity.

 After completion of study treatment, patients are followed up at 30 days and then every 4
 months for up to 1 year.
Inclusion Criteria:

 -  Histologically confirmed GEP NET, radiographically progressed on at least one line of
 standard therapy within the past 12 months

 -  Primary tumors may be in: pancreas, foregut (esophagus, stomach, duodenum),
 midgut (small intestine, appendix), hindgut (large intestine, rectum), or unknown
 origin

 -  Tumors may be functional (associated with clinical symptoms of hormone secretion)
 or non-functional

 -  Well-differentiated low grade (Ki67 index < 3% or mitotic index < 2 mitoses/10 high
 power fields [HPF]), or intermediate grade (Ki67 index 3-20% or mitotic index 2-20
 mitoses/10 HPF) NETs

 -  Metastatic or locally advanced unresectable disease

 -  Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) as
 per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1

 -  Prior or concurrent therapy with somatostatin analogs (SSAs) is allowed. If concurrent
 therapy, dose must be stable for at least 2 months

 -  Patients with carcinoid syndrome must have symptoms controlled with stable doses of
 SSAs for at least 2 months

 * Telotristat is not allowed

 -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

 -  Able to swallow oral medications

 -  Absolute neutrophil count >= 1500/uL

 -  Platelet count >= 100,000/uL (without platelet transfusion for at least two weeks)

 -  Hemoglobin >= 8 g/dL (blood transfusion is not allowed the day before or on the day of
 study treatment)

 -  Total bilirubin =< 1.5 times upper limit of normal (ULN)

 -  Transaminases (aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT])
 =< 3 x upper limit of normal (ULN) (=< 5 x ULN if liver metastases)

 -  Patients with Gilbert's syndrome with a total bilirubin =< 2.0 times ULN and direct
 bilirubin within normal limits are permitted

 -  International normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.5 x
 ULN

 -  Creatinine > 30 mL/min

 -  Ability to understand and sign the consent form

 -  Women of child-bearing potential must:

 -  Have a negative serum pregnancy test within 7 days prior to initiation of
 treatment, and

 -  Agree to use a highly effective method of contraception during the study and for
 at least 3 weeks following the last dose of study drug

 -  Men must be sterile or agree to use a highly effective method of contraception during
 the study and for at least 3 weeks following the last dose of study drug

 Exclusion Criteria:

 -  Poorly differentiated or high-grade GEP NETs (Ki67 index > 20% or mitotic index > 20
 mitoses/10 HPF)

 -  Prior treatment with abemaciclib or other CDK4/6 inhibitors

 -  Known hypersensitivity to abemaciclib or its components

 -  Receipt of any therapy or investigational agent within 4 weeks prior to study
 registration, except SSAs

 -  Any surgery, radiation, or embolization within 4 weeks

 -  Peptide receptor radionuclide therapy (PRRT) within 6 weeks

 -  Patients receiving other investigational agents

 -  Patients who have not recovered from adverse events of prior therapy to =< grade 1
 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events
 [CTCAE] version [v] 5), except for alopecia or grade =< 2 peripheral neuropathy prior
 to study treatment initiation. Subjects must have fully recovered from the acute
 effects of any prior radiotherapy

 -  Patients with untreated or symptomatic brain metastases (must be off corticosteroids
 for >= 4 weeks)

 -  Uncontrolled or untreated intercurrent illness including, but not limited to, active
 bacterial or fungal infection, congestive heart failure, severe/unstable angina,
 syncope of cardiac etiology, ventricular arrythmia (including but not limited to
 ventricular tachycardia, ventricular fibrillation), history of cardiac arrest,
 interstitial lung disease, severe dyspnea at rest or requiring oxygen supplementation,
 arterial or venous thrombotic event, pre-existing chronic condition resulting in
 baseline grade >= 2 diarrhea, or psychiatric illness/social situations that would
 limit compliance with study requirements

 -  Gastrointestinal tract disease resulting in an inability to take oral medication or a
 requirement for intravenous (IV) alimentation, prior surgical procedures involving
 stomach or small bowel in the last 28 days, active peptic ulcer disease, Crohn's
 disease or ulcerative colitis

 -  Known history of infection with human immunodeficiency virus (HIV)

 -  Active untreated infection with hepatitis B virus (i.e. hepatitis B surface antigen
 positive) or hepatitis C virus (i.e. hepatitis C antibody and ribonucleic acid [RNA]
 positive)

 -  Other malignancy diagnosed or recurrent in the past 3 years (except non-melanoma skin
 cancer and in-situ cervical cancer)

 -  Pregnancy or breast-feeding