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.
- 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
- Available archival tumor tissue (formalin-fixed paraffin-embedded [FFPE]) or willing to provide a fresh tumor biopsy
- 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 (without blood transfusion for at least two weeks)
- 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
- Serum creatinine =< 1.5 x ULN
- 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 months 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 months following the last dose of study drug
- 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 within 6 weeks
- Patients receiving other investigational agents
- Patients who have not recovered from adverse events (AEs) of prior therapy to =< grade 1 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5), except for alopecia
- 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 infection, congestive heart failure, severe/unstable angina, interstitial lung disease, severe dyspnea at rest or requiring oxygen supplementation, arterial or venous thrombotic event, 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
- Other malignancy diagnosed or recurrent in the past 3 years (except non-melanoma skin cancer and in-situ cervical cancer)
- Pregnancy or breast-feeding
Locations & Contacts
Status: In review
Contact: Stephen Leong
Status: Temporarily closed to accrual
Contact: Kaylyn Kit Man Wong
Trial Objectives and Outline
I. Evaluate the objective response rate (ORR) with abemaciclib in patients with advanced and refractory well-differentiated gastroenteropancreatic (GEP) neuroendocrine tumors (NETs).
I. Assess the progression-free survival (PFS) and overall survival (OS) rates at one year in GEP NETs overall.
II. Assess the antitumor activity of abemaciclib (ORR, 1-year PFS and OS rates) separately in carcinoid tumors and PNETs.
III. Assess the safety of abemaciclib in patients with advanced and refractory GEP NETs.
I. Evaluate the genomic and molecular biomarkers related to the CDK4/6 pathway that may predict abemaciclib efficacy in well-differentiated GEP NETs.
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.
Trial Phase & Type
Fred Hutch / University of Washington Cancer Consortium
Kaylyn Kit Man Wong
Secondary IDs NCI-2019-01490, I3Y-US-I007
Clinicaltrials.gov ID NCT03891784