Megestrol Acetate With or Without Pterostilbene in Treating Patients With Endometrial Cancer Undergoing Hysterectomy

This phase II trial studies how well megestrol acetate with or without pterostilbene works in treating patients with endometrial cancer undergoing hysterectomy. Drugs used in chemotherapy, such as megestrol acetate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Pterostilbene is an antioxidant found in blueberries or grapes, and it has been shown to be effective in killing tumor cells and reducing cancer burden. It is not yet known whether giving megestrol acetate with or without pterostilbene may work better in treating patients with endometrial cancer.

PRIMARY OBJECTIVE:

I. Determine the effect of megestrol acetate (MA) plus pterostilbene (PTE) versus MA alone on tumor proliferation (Ki-67) during the preoperative window in patients with endometrial cancer (EC) who are scheduled for hysterectomy.

EXPLORATORY OBJECTIVES:

I. Determine the effect of MA plus PTE versus MA alone on histologic response during the preoperative window in patients with EC or endometrial complex atypical hyperplasia who are scheduled for hysterectomy.

II. Explore biological characteristics of tumors to determine potential biomarkers which could select for treatment eligibility in future studies.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive pterostilbene orally (PO) twice daily (BID) and megestrol acetate PO BID for 3 weeks in the absence of disease progression or unaccepted toxicity.

ARM II: Patients receive megestrol acetate PO BID for 3 weeks in the absence of disease progression or unaccepted toxicity.

After completion of study treatment, patients are followed up at 6 weeks.

Eligibility Criteria:
Inclusion Criteria:

* Documented informed consent of the participant and/or legally authorized representative
* Willing to undergo an intraoperative biopsy/or standard of care tissue collection during surgery, following completion of treatment with MA +/- PTE
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Histologically confirmed EC or complex atypical hyperplasia of the endometrium
* Candidate for a total hysterectomy with or without bilateral salpingo-oophorectomy
* About to initiate preoperative window period, with planned hysterectomy scheduled
* Platelets \>= 100,000/mm\^3

  * NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement
* Total bilirubin =\< 1.5 X upper limit of normal (ULN)
* Aspartate aminotransferase (AST) =\< 1.5 x ULN
* Alanine aminotransferase (ALT) =\< 1.5 x ULN
* Creatinine clearance of \>= 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula
* Women of childbearing potential: negative urine or serum pregnancy test in premenopausal women. Postmenopausal women do not need to undergo a pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

Exclusion Criteria:

* Pterostilbene supplements within 30 days prior to day 1 of protocol therapy
* Any of the following phytochemical-based supplements within 30 days prior to day 1 of protocol therapy: resveratrol, genistein, and quercetin
* Chemotherapy for EC
* Allergic reaction/hypersensitivity to similar agents, excipients
* Unstable cardiac disease as defined by one of the following:

  * Cardiac events such as myocardial infarction (MI) within the past 6 months
  * NYHA (New York Heart Association) heart failure class III-IV
  * Uncontrolled atrial fibrillation or hypertensive emergency/urgency (defined as systolic blood pressure \>= 180 mmHg and/or diastolic blood pressure \>= 120 mmHg)
* Active or history of recent thromboembolism or stroke, within the past 6 months
* Cushing's syndrome
* Acute infection requiring systemic (intravenous) treatment
* Known history of human immunodeficiency virus (HIV) infection
* Known active hepatitis B or C infection
* Inability to swallow tablets/capsules
* Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc
* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)