Management of Atypical Endometrial Hyperplasia and Endometrial Carcinoma Using Megestrol Acetate

The trial's objectives are to study the efficacy, defined as complete pathologic resolution
of disease, of a standard hormonal regimen with the progestin Megace for the treatment of
atypical endometrial hyperplasia or well or moderately differentiated endometrial carcinoma
in women desiring conservative medical management of these conditions in the Women's Cancer
Program at the NYU School of Medicine and at the Bellevue Gynecologic Oncology clinics.

The major endpoint is pathologic complete response (pCR). For the purposes of this study,
patients will be reevaluated for response every 12 weeks until complete response. Response
will be assessed within 4 weeks of completion of 12 weeks of Megace, by endometrial biopsy or
dilation and curettage (D&C)/hysteroscopy. An endometrial biopsy is sufficient to document
progressive, stable disease or partial response. A D&C is necessary to confirm complete
response.

Patients whose disease has completely responded will discontinue treatment and be encouraged
to pursue fertility. Those not desiring immediate fertility will be placed on low dose oral
contraceptive pills for at least 6 months. Patients who have had either a partial response or
stable disease will be recounseled and offered continued medical management or surgical
therapy. Patients whose disease has progressed will be offered definitive surgical
management. Those patients declining surgery will still be followed on study.

Inclusion Criteria:

- Women with a diagnosis of atypical endometrial hyperplasia or G1 or G2 endometrial
carcinoma confirmed by an New York University (NYU) pathologist desiring medical
management will be eligible. The diagnosis may be obtained either by endometrial
biopsy or D&C. If diagnosis has been made outside of NYU, slides must be available for
review.

- Age > = 18 years.

- Life expectancy of greater than 12 months.

- Gynecologic Oncology Group (GOG) performance status score of 0, 1 or 2

- Patients must have normal organ and marrow function as defined below:

- leukocytes > = 3,000/mcL

- platelets > = 100,000/mcL

- total bilirubin within normal institutional limits

- AST(SGOT)/ALT(SGPT) no greater than 2.5 X institutional upper limit of Normal

- glucose < 200 mg/dl

- creatinine within normal institutional limits OR

- creatinine clearance > = 60 mL/min/1.73 m2 for patients with creatinine levels
above institutional normal

- Eligibility of patients receiving any medications or substances known to affect or
with the potential to affect the activity or pharmacokinetics of Megace will be
determined following review of their case by the Principal Investigator.

- The effects of Megace on the developing human fetus at the recommended therapeutic
dose are unknown. For this reason and because Megace is known to be teratogenic, women
of child-bearing potential and men must agree to use adequate contraception (hormonal
or barrier method of birth control; abstinence) prior to study entry and for the
duration of study participation. Should a woman become pregnant or suspect she is
pregnant while participating in this study, she should inform her treating physician
immediately.

- Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

- Patients with a histological diagnosis of clear cell, papillary serous or poorly
differentiated (G3) endometrial carcinoma.

- Patients with cancer have an MRI showing evidence of extrauterine spread or myometrial
invasion.

- Presence of US findings suspicious for ovarian malignancy, unclear endometrial primary
or recurrent endometrial cancer.

- Patients receiving other investigational agents.

- Patients with a history of a previous thrombotic event, known thrombophilic condition
or poorly controlled diabetes.

- Patients with a history of breast cancer or other hormonally responsive malignancy.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Pregnant women are excluded from this study because Megace has the potential for
teratogenic or abortifacient effects. Because there is an unknown but potential risk
for adverse events in nursing infants secondary to treatment of the mother with
Megace, breastfeeding should be discontinued if the mother is treated with Megace.