Megestrol Acetate Compared With Megestrol Acetate and Metformin to Prevent Endometrial Cancer

• Status: Recruiting
• Trial end date: 2023-10-31
• Target enrollment: 0
• Participant gender: All

Summary

This phase II trial studies the effect of megestrol acetate alone or in combination with metformin in preventing the progression of uterine pre-cancer (endometrial intraepithelial neoplasia) to endometrial cancer. Megestrol acetate is a drug used to block estrogen and suppress the effects of estrogen and androgens. It is the current non-surgical treatment of endometrial intraepithelial neoplasia. Metformin is a drug that has been found to have anti-cancer properties. Giving metformin and megestrol acetate together may decrease the growth of endometrial intraepithelial neoplasia in the uterus better than megestrol alone.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Megestrol; Megestrol Acetate; Metformin

Criteria

Inclusion Criteria:

• Participants with endometrial intraepithelial neoplasia (EIN) on an endometrial biopsy or dilation and curettage specimen will be eligible. Participants can be diagnosed with EIN at any time in the three months prior to surgery. Other commonly used pathologic terms for EIN, such as complex atypical hyperplasia and atypical hyperplasia will also be eligible

• No prior therapy for EIN is permitted

• Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)

• Total bilirubin =< 1.5 x institutional upper limit of normal

• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x institutional upper limit of normal

• Creatinine =< 1.5 x institutional upper limit of normal

• If the participant is diabetic, blood glucose must be appropriately controlled as evidenced by a hemoglobin A1c of < 8.0 in the last three months prior to enrollment. If no A1c is available, it will be drawn with baseline laboratory parameters as is standard of care prior to hysterectomy. For women who are diabetics who are on insulin, metformin can cause relative hypoglycemia. Women who are diabetic and receiving insulin will be allowed to participate, but will be asked to monitor their blood glucoses closely and alert the study team if persistent hypoglycemia is noted

• Must be a candidate and accepting of surgical management of EIN with planned hysterectomy

• The effects of megestrol acetate on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential must agree to use adequate contraception (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 study physician immediately. For metformin, published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk. Metformin can increase the potential for unintended pregnancy in premenopausal women as therapy with metformin may result in ovulation in some anovulatory women

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

• Participants who are cancer survivors, provided they are without evidence of active disease are eligible

• Participants who are human immunodeficiency virus (HIV)-positive will be eligible for participation

Exclusion Criteria:

• No current hormonal therapy or hormone replacement therapy (prior use of oral contraceptives or hormonal replacement therapy is allowed, provided that it was discontinued > 3 months from trial enrollment). Vaginal estrogen use is permitted

• No current use of metformin therapy (prior use of metformin therapy is allowed, provided that it was discontinued > 1 year from trial enrollment)

• Not currently breastfeeding or pregnant

• Participants may not be receiving any other investigational agents within 30 days of enrollment or during this study

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to metformin or megestrol acetate

• 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 it requires hysterectomy which is contraindicated in women who are pregnant and wish to continue the pregnancy, additionally, megestrol acetate is a category D agent. Megestrol acetate may cause fetal harm when administered to a pregnant woman. Fertility and reproduction studies with high doses of megestrol acetate have shown a reversible feminizing effect on some male rat fetuses. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with megestrol acetate, breastfeeding should be discontinued if the mother is treated with megestrol acetate

• Personal history of pulmonary embolism or deep vein thrombosis

• Women who are diabetics on insulin will be eligible to participate but they will be required to check their blood sugar regularly. Patients who are unable to check their blood sugar will be excluded from participation

• Women who are diabetics taking sulfonylureas and meglitinides will be excluded

• Women with an alcohol use or abuse disorder due to increased risk of lactic acidosis with metformin

• Current use of dofetilide, ulipristal, or carbonic anhydrase inhibitors as well as drugs that reduce metformin clearance such as ranolazine, vandetanib, dolutegravir, or cimetidine