50 Participants Needed

Megestrol + Metformin for Endometrial Cancer Prevention

Recruiting at 8 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 3 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires participants to stop using certain medications, such as current hormonal contraceptives, post-menopausal hormone replacement therapy, selective estrogen receptor modulators, aromatase inhibitors, and metformin. If you are taking any of these, you will need to discontinue them before enrolling in the study. Other medications may also need to be reviewed by the study team.

What data supports the effectiveness of the drug Megestrol + Metformin for Endometrial Cancer Prevention?

Research shows that combining metformin with megestrol acetate can be more effective than using megestrol acetate alone for treating conditions like atypical endometrial hyperplasia and well-differentiated endometrial cancer, which are related to endometrial cancer.12345

Is the combination of Megestrol and Metformin safe for humans?

Megestrol acetate has been used in postmenopausal women for endometrial conditions with no major side effects reported, but it can cause severe high blood sugar in some cases. Metformin is generally used for diabetes and has been suggested to have anticancer properties, but specific safety data for the combination with Megestrol is limited.25678

How is the drug Megestrol + Metformin unique for endometrial cancer prevention?

The combination of Megestrol Acetate and Metformin is unique because it combines a hormone therapy with a drug that has anticancer properties, potentially enhancing the treatment's effectiveness in preventing endometrial cancer. This approach is different from using Megestrol Acetate alone, as Metformin may help inhibit cell growth and tumor development.267910

Research Team

EB

Emma Barber

Principal Investigator

Northwestern University

Eligibility Criteria

This trial is for adults with a pre-cancerous condition of the uterus called endometrial intraepithelial neoplasia (EIN), who are planning to have a hysterectomy. They must be in good health, not pregnant, and willing to use birth control if they can have children. People with certain viral infections must be on treatment with an undetectable viral load.

Inclusion Criteria

I am on long-term antiviral treatment for herpes.
I am willing to undergo a hysterectomy for my endometrial condition.
I am HIV positive, on treatment, and my viral load has been undetectable for the last 6 months.
See 11 more

Exclusion Criteria

I am not a diabetic woman taking sulfonylureas or meglitinides.
I am not pregnant as the study requires surgery and medication that could harm a fetus.
I am not breastfeeding as it may harm my nursing infant due to my treatment.
See 10 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive megestrol acetate alone or in combination with metformin for 21-35 days prior to a planned procedure

3-5 weeks
Daily oral administration

Procedure and Biopsy

Participants undergo a planned procedure (hysterectomy or IUD placement) and biopsy on the day of the procedure

1 day
1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks
Follow-up visits as needed

Treatment Details

Interventions

  • Extended Release Metformin Hydrochloride
  • Megestrol Acetate
Trial OverviewThe study is testing whether taking megestrol acetate alone or combined with metformin prevents EIN from turning into uterine cancer better than just megestrol acetate. Participants will receive these medications before their planned surgery to remove the uterus.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm II (megestrol acetate, metformin hydrochloride)Experimental Treatment4 Interventions
Prior to standard of care planned procedure, patients receive megestrol acetate PO BID and metformin hydrochloride extended-release PO BID for 21-35 days (up to and including the night before planned procedure) in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy on the day of planned procedure.
Group II: Arm I (megestrol acetate)Active Control3 Interventions
Prior to standard of care planned procedure, patients receive megestrol acetate PO BID for 21-35 days (up to and including the night before planned procedure) in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy on the day of planned procedure.

Megestrol Acetate is already approved in United States, European Union, Canada for the following indications:

🇺🇸
Approved in United States as Megace for:
  • Breast cancer
  • Endometrial cancer
  • Prostate cancer
  • Appetite stimulation
🇪🇺
Approved in European Union as Megestrol for:
  • Breast cancer
  • Endometrial cancer
  • Prostate cancer
  • Appetite stimulation
🇨🇦
Approved in Canada as Megace for:
  • Breast cancer
  • Endometrial cancer
  • Prostate cancer
  • Appetite stimulation

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Findings from Research

In a study of 150 patients with atypical endometrial hyperplasia (AEH) or endometrioid endometrial cancer (EEC), the combination of metformin and megestrol acetate (MA) showed a higher complete response rate at 16 weeks compared to MA alone, particularly in AEH patients (39.6% vs. 20.4%).
The combination treatment was especially effective in non-obese and insulin-sensitive AEH patients, suggesting that metformin may enhance the efficacy of MA in fertility-sparing treatments.
Metformin plus megestrol acetate compared with megestrol acetate alone as fertility-sparing treatment in patients with atypical endometrial hyperplasia and well-differentiated endometrial cancer: a randomised controlled trial.Yang, BY., Gulinazi, Y., Du, Y., et al.[2020]
In a pilot study of 16 patients with endometrial atypical hyperplasia, the combination of metformin and megestrol acetate (MA) showed a higher complete response rate of 75% compared to 25% for MA alone, suggesting that metformin may enhance treatment efficacy.
The presence of metabolic syndrome did not significantly impact the treatment response, indicating that metformin plus MA could be a viable option for patients regardless of their metabolic status, with no irreversible toxicities reported.
Conservative therapy with metformin plus megestrol acetate for endometrial atypical hyperplasia.Shan, W., Wang, C., Zhang, Z., et al.[2021]
In a study of 4 young women with stage IA grade 2 endometrial carcinoma seeking to preserve fertility, 75% achieved a complete response to treatment with megestrol acetate, and some received metformin for metabolic syndrome.
The results suggest that megestrol acetate, with or without metformin, combined with regular hysteroscopic examinations, may be an effective fertility-sparing treatment option for this type of cancer.
Conservative management of grade 2 stage IA endometrial carcinoma and literature review.Shan, W., Wu, P., Yang, B., et al.[2021]

References

Metformin plus megestrol acetate compared with megestrol acetate alone as fertility-sparing treatment in patients with atypical endometrial hyperplasia and well-differentiated endometrial cancer: a randomised controlled trial. [2020]
Conservative therapy with metformin plus megestrol acetate for endometrial atypical hyperplasia. [2021]
Conservative management of grade 2 stage IA endometrial carcinoma and literature review. [2021]
Surgical safety and personal costs in morbidly obese, multimorbid patients diagnosed with early-stage endometrial cancer having a hysterectomy. [2020]
Metabolic effects associated with high-dose continuous megestrol acetate administration in the treatment of endometrial pathology. [2019]
Hormonal therapy for lesions of the endometrium. [2018]
The impact of adjunctive metformin to progesterone for the treatment of non-atypical endometrial hyperplasia in a randomized fashion, a placebo-controlled, double blind clinical trial. [2021]
Hyperglycemia secondary to megestrol acetate for endometrial neoplasia. [2013]
Progestin therapy in lesions of the endometrium. [2013]
10.United Statespubmed.ncbi.nlm.nih.gov
Hysteroscopic Curettage Followed by Megestrol Acetate Plus Metformin as a Fertility-Sparing Treatment for Women with Atypical Endometrial Hyperplasia or Well-Differentiated Endometrioid Endometrial Carcinoma. [2022]