Clinical Trials /

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

NCT03891784

Description:

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.

Related Conditions:
  • Appendix Neuroendocrine Tumor
  • Colorectal Neuroendocrine Tumor
  • Duodenal Neuroendocrine Tumor
  • Esophageal Neuroendocrine Tumor
  • Gastric Neuroendocrine Tumor
  • Pancreatic Neuroendocrine Tumor
  • Small Intestinal Neuroendocrine Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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)

Clinical Trial IDs

  • ORG STUDY ID: RG1004456
  • SECONDARY ID: NCI-2019-01490
  • SECONDARY ID: 9959
  • NCT ID: NCT03891784

Conditions

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

Interventions

DrugSynonymsArms
AbemaciclibVerzenio, 1231929-97-7, 2-PyrimidinamineTreatment (abemaciclib)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (abemaciclib)ExperimentalPatients receive abemaciclib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Abemaciclib

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]), 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

        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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Up to 1 year
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure: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
Safety Issue:
Description: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.
Measure:Overall survival
Time Frame:Time from study registration to death of any cause, assessed up to 1 year
Safety Issue:
Description: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.
Measure:Incidence of adverse events
Time Frame:Up to 30 days
Safety Issue:
Description:Safety will be evaluated by assessing the adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Washington

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