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

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ClinicalTrials.gov Identifier: NCT03891784
Recruitment Status : Not yet recruiting
First Posted : March 27, 2019
Last Update Posted : July 16, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Washington

Tracking Information
First Submitted Date  ICMJE March 25, 2019
First Posted Date  ICMJE March 27, 2019
Last Update Posted Date July 16, 2019
Estimated Study Start Date  ICMJE August 15, 2019
Estimated Primary Completion Date September 30, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History Complete list of historical versions of study NCT03891784 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Abemaciclib in Treating Patients With Advanced, Refractory, and Unresectable Digestive System Neuroendocrine Tumors
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE Drug: Abemaciclib
Given PO
Other Names:
  • Verzenio
  • 1231929-97-7
  • 2-Pyrimidinamine
Study Arms  ICMJE 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: March 25, 2019)
37
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 30, 2024
Estimated Primary Completion Date September 30, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kaylyn Kit Man Wong 206-606-2038 kkmwong@seattlecca.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03891784
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: No
Responsible Party University of Washington
Study Sponsor  ICMJE University of Washington
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Kaylyn Kit Man Wong Fred Hutch/University of Washington Cancer Consortium
PRS Account University of Washington
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP