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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
27
Given PO
Given PO
Undergo standard of care hysterectomy
Northwestern University
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Changes in Ki-67 expression
Time frame: Baseline up to 6 weeks
Proportion of tumors with complete cell cycle arrest (CCCA) response
Will be measured by Ki-67 between the pre-treatment tumor and the post-treatment tumor. CCCA response is defined as less than 3% of tumor cells staining positive for Ki-67 from specimens obtained at time of hysterectomy. Baseline biomarker levels will be compared between patients who do vs. do not achieve complete CCCA using a two-sample t-test.
Time frame: At day 15
Biological characteristics of tumors: MMR status
Will be measured to correlate with decreased Ki-67 expression induced by the letrozole and abemaciclib combination.
Time frame: Up to 6 weeks
Biological characteristics of tumors: PTEN mutational status
Will be measured to correlate with decreased Ki-67 expression induced by the letrozole and abemaciclib combination.
Time frame: Up to 6 weeks
Biological characteristics of tumors: expression of cyclin D1
Will be measured to correlate with decreased Ki-67 expression induced by the letrozole and abemaciclib combination.
Time frame: Up to 6 weeks
Biological characteristics of tumors: p16
Will be measured to correlate with decreased Ki-67 expression induced by the letrozole and abemaciclib combination.
Time frame: Up to 6 weeks
Biological characteristics of tumors: pRB
Will be measured to correlate with decreased Ki-67 expression induced by the letrozole and abemaciclib combination.
Time frame: Up to 6 weeks
Incidence of adverse events associated with abemaciclib and letrozole
Categorized and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.
Time frame: Up to 6 weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.