Abemaciclib in Treating Patients With Advanced, Refractory, and Unresectable Digestive System Neuroendocrine Tumors

• ClinicalTrials.gov Identifier: NCT03891784
• Recruitment Status: Recruiting
• First Posted: March 27, 2019
• Last Update Posted: January 26, 2023
• Sponsor: University of Washington
• Collaborator: Eli Lilly and Company
• Information provided by (Responsible Party): University of Washington

Tracking Information

• First Submitted Date: March 25, 2019
• First Posted Date: March 27, 2019
• Last Update Posted Date: January 26, 2023
• Actual Study Start Date: October 31, 2019
• Estimated Primary Completion Date: September 30, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 25, 2019)

Objective response rate (ORR) [ Time Frame: Up to 1 year ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 25, 2019)

• Progression-free survival [ Time Frame: From study registration to radiographic progression per RECIST v1.1 (investigator assessment), clinical progression, or death of any cause, assessed up to 1 year ]
  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.
• Overall survival [ Time Frame: Time from study registration to death of any cause, assessed up to 1 year ]
  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.
• Incidence of adverse events [ Time Frame: Up to 30 days ]
  Safety will be evaluated by assessing the adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Abemaciclib in Treating Patients With Advanced, Refractory, and Unresectable Digestive System Neuroendocrine Tumors
• Official Title: A Phase 2 Trial of the CDK4/6 Inhibitor Abemaciclib in Patients With Advanced and Refractory Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors (GEP NETs)
• Brief Summary: 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.

Detailed Description

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

Intervention

Drug: Abemaciclib

Given PO

Other Names:

• Verzenio
• 1231929-97-7
• 2-Pyrimidinamine

Study Arms

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.

Intervention: Drug: Abemaciclib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 25, 2019): 37
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 30, 2024
• Estimated Primary Completion Date: September 30, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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]), intermediate grade (Ki67 index 3-20% or mitotic index 2-20 mitoses/10 HPF) NETs, or high grade (Ki67 index >20% but ≤55%, or mitotic index >20 but ≤ 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

Exclusion Criteria:

• 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
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: David B. Zhen; 206-606-1733; dbzhen@uw.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03891784
• Other Study ID Numbers: RG1004456; NCI-2019-01490 ( Registry Identifier: NCI / CTRP ); 9959 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University of Washington
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Washington
• Original Study Sponsor: Same as current
• Collaborators: Eli Lilly and Company

Investigators

• Principal Investigator: David B. Zhen; Fred Hutch/University of Washington Cancer Consortium

• PRS Account: University of Washington
• Verification Date: January 2023