A Pre-Op Window Study Evaluating Anti-Proliferative Effects of Atorvastatin on the Endometrium

This is a preoperative window, phase 0 study of short-term atorvastatin treatment in obese
women who are to undergo surgical staging for endometrial cancer. After recruitment is
completed, 24 paired endometrial biopsies and hysterectomy specimens from endometrial cancer
patients treated at UNC will be retrospectively obtained from the Department of Pathology to
serve as controls. These cases will be matched for stage and grade to the endometrial cancers
of those women enrolled on this phase 0 clinical trial and will undergo the same
immunohistochemical analysis. Two previous phase 0 window studies of metformin in endometrial
cancer have found no difference in Ki-67 expression between preoperative endometrial biopsy
and hysterectomy specimen in control patients, although a difference was seen in metformin
treated patients. However, the investigators plan to include a control group to ensure that
changes found between pre- and post-atrovastatin treated patients are due to the effects of
this drug versus differences in the type of specimen examined (i.e. endometrial biopsy
specimen obtained in clinic versus hysterectomy specimen obtained at the time of surgery). In
addition, enrolled patients will undergo repeat endometrial biopsy post- atorvastatin
treatment at the time of their surgical staging. Thus, study investigators plan to compare
pre-treatment endometrial biopsies to both post-treatment endometrial biopsies and
hysterectomy specimens as well as have a historical control group.

Inclusion Criteria:

- Be between the ages of 18-75 years old

- Have a confirmed diagnosis of type I endometrial cancer (endometrioid) based on
pre-operative endometrial biopsy or dilation and curettage (D&C)

- Have a BMI >30

- Have no contraindication to short-term atorvastatin therapy

- Have a serum creatinine ≤ 1.0 mg/dL

- Have normal serum transaminase values (AST and ALT)

- Need to be able to undergo atorvastatin treatment for a minimum of 2 weeks but no more
than a maximum of 4 weeks prior to surgical staging

Exclusion Criteria:

- Are currently taking a statin or have taken a statin in the past 6 months or have a
history of an allergic reaction or intolerance at any time to a statin

- Have a history of liver or renal dysfunction

- Have a history of alcoholism

- Are pregnant

- Are currently taking any hormonal therapy or have been on hormonal therapy in the past
4 weeks

- Are taking a drug that may significantly interact or influence the metabolism of
atorvastatin

- Concomitant cyclosporine, gemfibrizol, telaprevir, or tipranavir/ritonavir use

- History of stroke or transient ischemic attack in the preceding 6 months