Abemaciclib and Letrozole in Treating Patients With Endometrial Cancer

NCT04049227 | Completed Early Phase 1 DMC FDA Drug

• 4 other identifiers: NU 18G07STU00209370P30CA060553NCI-2019-04599
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 2

Brief Summary

This early phase I trial studies how well abemaciclib and letrozole work in treating patients with endometrial cancer and determines whether there are changes in patients' cancer cell biomarkers (a genetic feature or specific protein) for cell growth before and after treatment. Antihormone therapy with aromatase inhibitors, such as letrozole, may lessen the amount of estrogen made by the body. Abemaciclib blocks the activities of a class of proteins called cyclin-dependent kinase, which are involved in cell duplication. Giving letrozole and abemaciclib together may slow down cancer cell growth in patients with endometrial cancer.

Conditions

Endometrial Endometrioid Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Changes in Ki-67 expression

  Baseline up to 6 weeks

Secondary Outcomes (7)

• Proportion of tumors with complete cell cycle arrest (CCCA) response

  At day 15

• Biological characteristics of tumors: MMR status

  Up to 6 weeks

• Biological characteristics of tumors: PTEN mutational status

  Up to 6 weeks

• Biological characteristics of tumors: expression of cyclin D1

  Up to 6 weeks

• Biological characteristics of tumors: p16

  Up to 6 weeks

Study Arms (1)

Treatment (letrozole, abemaciclib)

EXPERIMENTAL

Patients receive letrozole PO QD and abemaciclib PO BID on days 1-14. Patients then undergo standard of care hysterectomy on day 15.

Drug: Abemaciclib; Drug: Letrozole; Procedure: Therapeutic Conventional Surgery

Interventions

Abemaciclib DRUG

Given PO

Also known as: LY-2835219, LY2835219, Verzenio

Treatment (letrozole, abemaciclib)

Letrozole DRUG

Given PO

Also known as: CGS 20267, Femara

Treatment (letrozole, abemaciclib)

Therapeutic Conventional Surgery PROCEDURE

Undergo standard of care hysterectomy

Treatment (letrozole, abemaciclib)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a new histologically confirmed diagnosis of endometrioid adenocarcinoma of the endometrium who are candidates for hysterectomy.
• Note: Patients with recurrent disease are not eligible.
• Patients must be willing to provide archival tumor biopsy slides from the specimen (e.g. endometrial biopsy or dilation and curettage) which diagnosed them with endometrial cancer.
• (Please note: Given the amount of tissue obtained from these specimens is often much more than a core needle biopsy, we do not anticipate difficulties with insufficient tissue.)
• Patients should be treatment naive. They should not have received any endometrial cancer directed therapy including medroxyprogesterone acetate, aromatase inhibitors, other hormonal treatments or radiation therapy for treatment of endometrial cancer.
• Note: Patients can have used oral contraceptives or hormonal replacement therapy provided these were discontinued 28 days prior to trial enrollment.
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 within 28 days prior to registration for protocol therapy.
• Patients must have adequate organ function for all of the following criteria within 28 days of registration.
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9 /L (within 28 days of registration).
• Platelets \>= 100 x 10\^9 /L (within 28 days of registration).
• Hemoglobin \>= 8 g/dL (within 28 days of registration).
• Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (within 28 days of registration).
• Patients with Gilbert?s syndrome with a total bilirubin =\< 2.0 times ULN and direct bilirubin within normal limits are permitted.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN (within 28 days of registration).

You may not qualify if:

• Patients who have had chemotherapy, hormonal therapy or radiotherapy directed at the treatment of endometrial cancer prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks prior to registration are not eligible.
• Patients may not be receiving any other investigational agents. A wash out period of 4 weeks before registration is required for eligibility.
• Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to abemaciclib or letrozole or any of its excipients are not eligible.
• Patients receiving CYP3A inducers or strong CYP3A inhibitors will not be eligible for this study. A wash-out period of minimum 5 half-lives or 7 days, whichever is shorter, before registration is required for the patient to become eligible.
• Patients who have a known personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest are not eligible.
• Patients who have known active bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus \[HIV\] positivity or with known active hepatitis B or C (for example, hepatitis B surface antigen positive). Screening is not required for enrollment.
• Note: patients with uncomplicated urinary tract infection or uncomplicated cystitis are eligible.
• Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:
• Hypertension that is not controlled on medication
• Baseline grade 2 or higher diarrhea.
• Ongoing or active infection requiring systemic treatment.
• Symptomatic congestive heart failure.
• Unstable angina pectoris.
• Psychiatric illness that would limit compliance with study requirements.
• Social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Interventions

abemaciclib; Letrozole

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Emma Barber, MD, MS

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2019
• First Posted: August 8, 2019
• Study Start: August 12, 2019
• Primary Completion: April 1, 2023
• Study Completion: May 15, 2023
• Last Updated: October 20, 2025

Record last verified: 2025-10

Locations

US (2)