Abemaciclib and Letrozole in Treating Patients With Endometrial Cancer

  • STATUS
    Recruiting
  • End date
    Jul 1, 2023
  • participants needed
    27
  • sponsor
    Northwestern University
Updated on 15 May 2021

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.

Description

PRIMARY OBJECTIVES:

I. To determine whether there are changes in Ki-67 expression from the pretreatment specimen (e.g. biopsy or dilation and curettage [D&C]) to the post-treatment hysterectomy specimen following treatment with letrozole and abemaciclib.

SECONDARY OBJECTIVES:

I. To determine the proportion of tumors with complete cell cycle arrest (CCCA) response as measured by Ki-67 expression between the pre-treatment tumor and the posttreatment tumor.

II. To identify biological characteristics of tumors (e.g. mismatch repair [MMR] status, PTEN mutational status, etc.) correlating with decreased Ki-67 expression induced by the letrozole and abemaciclib combination.

III. To determine the frequency of adverse events associated with use of abemaciclib and letrozole.

EXPLORATORY OBJECTIVES:

I. To evaluate the correlation of the expression of Ki-67 with that of cyclin D1, p16, pRB, and PTEN as well as with MMR deficiency.

OUTLINE

Patients receive letrozole orally (PO) once daily (QD) and abemaciclib PO twice daily (BID) on days 1-14. Patients then undergo standard of care hysterectomy on day 15.

After completion of study treatment, patients are followed up at 30 days and at 2 and 6 weeks after surgery.

Details
Condition Endometrial Endometrioid Adenocarcinoma, endometrioid adenocarcinoma of the endometrium
Treatment Letrozole, therapeutic conventional surgery, Abemaciclib
Clinical Study IdentifierNCT04049227
SponsorNorthwestern University
Last Modified on15 May 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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)
Serum creatinine =< 1.5 x ULN (within 28 days of registration)
Patients with a history of surgical sterilization are eligible for this study. OR
Patients must have post-menopausal status due to menopause (surgical or natural). Patients must meet at least one of the following criteria
Bilateral oophorectomy
Age >= 55 years
Age =< 55 years and amenorrhea (absence of menstruation) for > 12 months OR
Patients who are not post-menopausal or previously sterilized
i.e. a female of childbearing potential (patients who are not post-menopausal), must have a negative serum pregnancy test within 7 days of the first dose of study treatment (abemaciclib and/or letrozole). Patient must agree to use adequate birth control (condoms with spermicidal agent or abstinence) while on the study and for 3 weeks after completion of treatment
Patients should be able to swallow oral medications
Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study
Patients must be willing and able to have a window of >= 15 days prior to their scheduled hysterectomy surgery after registration

Exclusion Criteria

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
Serious preexisting medical condition(s) that would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn?s disease or ulcerative colitis or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea)
Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient?s safety or study endpoints
Female patients who are pregnant or nursing are not eligible
Patients who are unable to retain oral medication, and patients who have gastrointestinal disorders or abnormalities that would interfere with absorption of the study drugs are not eligible
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

0/250
Preferred Language
Other Language
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note