Ignite Creation Date:
2025-12-24 @ 9:08 PM
Ignite Modification Date:
2026-01-01 @ 3:34 PM
Study NCT ID:
NCT04576104
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-12-02
First Post:
2020-10-03
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Megestrol Acetate Compared With Megestrol Acetate and Metformin to Prevent Endometrial Cancer
Sponsor:
Northwestern University
Organization:
Study Overview
Official Title:
Surgical Window of Opportunity Study of Megestrol Acetate Compared With Megestrol Acetate and Metformin for Endometrial Intraepithelial Neoplasia
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
Detailed Description:
PRIMARY OBJECTIVE:
I. To compare the change in endometrial cell proliferation, as measured by the percentage (%) of Ki-67 positive cells, in participants with endometrial intraepithelial neoplasia who undergo 4 weeks of treatment with megestrol acetate + metformin or megestrol acetate alone prior to planned procedure (hysterectomy) or progestin intrauterine device \[IUD\] placement).
SECONDARY OBJECTIVE:
I. To measure the changes in protein expression in the endometrial intraepithelial neoplasia lesion, using immunohistochemistry (i-vi) in subjects treated with megestrol acetate + metformin compared to those treated with megestrol acetate alone.
i. Estrogen receptor (ER) and progesterone receptor (PR) ii. PTEN/PAX2 expression iii. Markers of the PI3K-Akt-mTOR pathway (phosphor-acetyl-CoA carboxylase (ACC), p(Ser473)-Akt, phosphor-S6K, p4EBP1) iv. Markers of cell death (TUNEL, cleaved caspase-3) v. Markers of intratumoral insulin signaling (Phosphorylated insulin receptor (pIR) and insulin-like growth factor-1 receptor (total and phosphorylated IGF1R), vi. Mismatch repair (MMR) deficiency (baseline only).
EXPLORATORY OBJECTIVE:
I. To explore whether baseline Ki-67 expression and other clinical characteristics are associated with treatment response.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Prior to standard of care planned procedure, patients receive megestrol acetate orally (PO) twice daily (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.
ARM II: 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.
After completion of study treatment, patients are followed for up to 42 days.
I. To compare the change in endometrial cell proliferation, as measured by the percentage (%) of Ki-67 positive cells, in participants with endometrial intraepithelial neoplasia who undergo 4 weeks of treatment with megestrol acetate + metformin or megestrol acetate alone prior to planned procedure (hysterectomy) or progestin intrauterine device \[IUD\] placement).
SECONDARY OBJECTIVE:
I. To measure the changes in protein expression in the endometrial intraepithelial neoplasia lesion, using immunohistochemistry (i-vi) in subjects treated with megestrol acetate + metformin compared to those treated with megestrol acetate alone.
i. Estrogen receptor (ER) and progesterone receptor (PR) ii. PTEN/PAX2 expression iii. Markers of the PI3K-Akt-mTOR pathway (phosphor-acetyl-CoA carboxylase (ACC), p(Ser473)-Akt, phosphor-S6K, p4EBP1) iv. Markers of cell death (TUNEL, cleaved caspase-3) v. Markers of intratumoral insulin signaling (Phosphorylated insulin receptor (pIR) and insulin-like growth factor-1 receptor (total and phosphorylated IGF1R), vi. Mismatch repair (MMR) deficiency (baseline only).
EXPLORATORY OBJECTIVE:
I. To explore whether baseline Ki-67 expression and other clinical characteristics are associated with treatment response.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Prior to standard of care planned procedure, patients receive megestrol acetate orally (PO) twice daily (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.
ARM II: 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.
After completion of study treatment, patients are followed for up to 42 days.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2020-07529 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| NCI20-02-01 | OTHER | Northwestern University | View | |
| NWU20-02-01 | OTHER | DCP | View | |
| P30CA060553 | NIH | None | https://reporter.nih.gov/quic… | View |
| UG1CA242643 | NIH | None | https://reporter.nih.gov/quic… | View |