Abemaciclib In Treating Patients With Advanced, Refractory, And Unresectable Digestive System Neuroendocrine Tumors

Study Overview

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.

Advanced Digestive System Neuroendocrine Neoplasm
Digestive System Neuroendocrine Tumor
Foregut Neuroendocrine Tumor
Hindgut Neuroendocrine Tumor
Locally Advanced Unresectable Digestive System Neuroendocrine Neoplasm
Metastatic Digestive System Neuroendocrine Neoplasm
Midgut Neuroendocrine Tumor
Pancreatic Neuroendocrine Tumor
Refractory Digestive System Neuroendocrine Neoplasm

DRUG: Abemaciclib

RG1004456
NCI-2019-01490 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
9959 (OTHER Identifier) (OTHER: Fred Hutch/University of Washington Cancer Consortium)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2019-03-25	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-04-01
First Submitted that Met QC Criteria 2019-03-25	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-04-04
First Posted (ACTUAL) 2019-03-27	Results First Posted N/A	Last Verified 2025-04

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Treatment (abemaciclib) Patients receive abemaciclib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	DRUG: Abemaciclib Given PO

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment (abemaciclib)

Patients receive abemaciclib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

DRUG: Abemaciclib

Given PO

Primary Outcome Measures	Measure Description	Time Frame
Objective response rate (ORR)	ORR defined as complete or partial response as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1, will be represented by a waterfall plot.	Up to 1 year after completion of study treatment

Secondary Outcome Measures	Measure Description	Time Frame
Progression-free survival	The distribution for survival times will be estimated using the method of Kaplan-Meier; associated landmark time percentages and the median value will be based on this. Confidence intervals for median values will use the Brookmeyer-Crowley method. Survival outcomes between carcinoid tumors and pancreatic neuroendocrine tumor (PNET)s will be compared using a log-rank test.	From study registration to radiographic progression per RECIST v1.1 (investigator assessment), clinical progression, or death of any cause, assessed up to 1 year
Overall survival	The distribution for survival times will be estimated using the method of Kaplan-Meier; associated landmark time percentages and the median value will be based on this. Confidence intervals for median values will use the Brookmeyer-Crowley method. Survival outcomes between carcinoid tumors and PNETs will be compared using a log-rank test.	Time from study registration to death of any cause, assessed up to 1 year
Incidence of adverse events	Safety will be evaluated by assessing the adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.	Up to 30 days

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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 NET with low grade (Ki67 index < 3% or mitotic index < 2 mitoses/10 high power field [HPF]), intermediate grade (Ki67 index 3-20% or mitotic index 2-20 mitoses/10 HPF), or high grade (Ki67 21% to ≤ 55% of mitotic index 21-55% mitoses/10 HPF). In cases where pathology reports call out only a "high grade neuroendocrine carcinoma", such patients are eligible only if well differentiated status is confirmed by a board-certified pathologist AND Ki-67 is ≤ 55%
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
Age >= 18 years
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

Presence of poorly differentiated neuroendocrine carcinoma (NEC) or mixed adenoneuroendocrine carcinomas (MANECs)
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
Severe renal impairment (e.g. estimated creatinine clearance < 30ml/min)
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Eli Lilly and Company

Investigators

PRINCIPAL_INVESTIGATOR: David B. Zhen, Fred Hutch/University of Washington Cancer Consortium

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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Clinical Trial Record