Progestins for the Treatment of Endometrial Cancer or Precancers of the Uterus Before Surgery, The Pro-Window Trial

February 20, 2026 updated by: New Mexico Cancer Research Alliance

Evaluating Promising Progestins in Endometrial Cancer Through a Rotating Umbrella Surgical Window Trial - The PRO-WINDOW TRIAL for Endometrial Cancer

This phase II trial tests compares the effect of progestins, megestrol acetate to micronized progesterone, in treating patients with endometrial cancer and precancers of the uterus (atypical endometrial hyperplasia) before surgery. Progestins, similar to the natural hormone progesterone, are approved drugs used in birth control and hormone replacement pills, and some can treat uterine endometrial cancers. In the initial comparison of this rotating umbrella trial, megestrol acetate, a progestin, will be compared to micronized progesterone, a form of natural progesterone that is a hormone produced by body normally. Hormone therapy using megestrol acetate and micronized progesterone may be effective in treating patients with endometrial cancer or atypical endometrial hyperplasia before surgery, and understanding the tissue effects of each agent on the malignant endometrium will uncover novel mechanistic and biomarker data to understand how best to advanced hormone therapy for endometrial cancer.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. Perform an adaptive, master protocol, surgical window of opportunity rotating umbrella trial to assess the effectiveness of progestins in tissues from women with newly diagnosed endometrial cancer or atypical endometrial hyperplasia.

II. Establish biomarkers and molecular signatures of progestin efficacy in patients with endometrial cancer.

OUTLINE: Patients are randomized to 1 of 2 arms in the initial comparison.

ARM I: Patients undergo biopsy or curettage and then receive megestrol acetate orally (PO) twice daily (BID) 21-24 days prior to standard of care (SOC) hysterectomy on study.

ARM II: Patients undergo biopsy or curettage and then receive micronized progesterone PO once daily (QD) beginning 21-24 days prior to SOC hysterectomy on study.

After completion of study treatment, patients are followed up at 30-45 days after surgery.

Study Type

Interventional

Enrollment (Estimated)

140

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa/Holden Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Megan E. McDonald
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • University of New Mexico Cancer Center
        • Principal Investigator:
          • Carolyn Y. Muller
        • Contact:
    • Utah
      • Salt Lake City, Utah, United States, 84106
        • University of Utah Sugarhouse Health Center
        • Principal Investigator:
          • Kathryn Maurer
        • Contact:
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Cancer Center
        • Principal Investigator:
          • Linda R. Duska
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients must have a histologically proven diagnosis of endometrioid endometrial adenocarcinoma by endometrial curettage or biopsy within 8 weeks prior to registration. Pathology reports should document adequate tissue from the biopsy and slides should be reasonable determined to be obtainable by the study team for study use
  • History/physical examination within 42 +/- 5 days of planned surgical procedure (18-21 days from day 1)
  • Age ≥ 18
  • The trial is open only to women with primary endometrioid adenocarcinoma of the uterine corpus (all histologic grades and stages) who are planned and appropriate for primary surgical treatment to include removal of the uterine corpus via any surgical modality. The patient must be considered a suitable surgical candidate
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2, or 3 within 28 days prior to registration
  • Formalin-fixed, paraffin-embedded tumor tissue from the biopsy or curettage must be reasonably deemed available for submission along with the corresponding pathology report
  • Platelets ≥ 100,000/μl
  • Granulocytes (absolute neutrophil count [ANC]) ≥ 1,500/μl
  • Creatinine ≤ 1.6 mg/dl
  • Serum glutamic-pyruvic transaminase (SGPT) (alanine transaminase [ALT]) ≤ 3 x upper limits of normal
  • Bilirubin within institutional normal limits
  • The patient must provide study-specific informed consent and authorization permitting release of personal health information prior to study entry
  • Any patients of childbearing potential must have a negative pregnancy test

Exclusion Criteria:

  • Patients with any non-endometrioid histology (such as serous, clear cell, or carcinosarcoma or mixed)
  • Patients who have received prior progestin or anti-estrogen therapy during the 3 months before the diagnosis of endometrioid adenocarcinoma of the uterine corpus is established. Estrogen therapy alone is allowed
  • Patients with ECOG performance status of 4
  • Patients with history of deep venous thrombosis or pulmonary embolism within the past 2 years or ongoing thromboembolic disorders
  • Patients who have previously received systemic, radiation or other treatment for uterine cancer
  • Patients for whom formalin-fixed, paraffin-embedded tumor tissue from the biopsy or curettage is scant or unavailable
  • Patients with a suspected or known peanut allergy
  • Patients with serious comorbidities or gastrointestinal obstruction that precludes taking oral medications or have malabsorptive disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm I (biopsy, curettage, MPA, hysterectomy)
Patients undergo biopsy or curettage and then receive megestrol acetate PO BID 21-24 days prior to SOC hysterectomy on study.
Drug: Megestrol Acetate
Given PO
Other Names:
  • Megace
  • 17-Hydroxy-6-methylpregna-4,6-diene-3,20-dione acetate
  • 17.alpha.-Acetoxy-6-methylpregna-4,6-diene-3,20-dione
  • 6-Dehydro-6-methyl-17.alpha.-acetoxyprogesterone
  • 6-Methyl-6-dehydro-17.alpha.-acetoxyprogesterone
  • BDH 1298
  • BDH-1298
  • Maygace
  • Megestat
  • Megestil
  • Niagestin
  • Ovaban
  • Pallace
  • SC-10363
  • SC 10363
Procedure: Hysterectomy
Undergo hysterectomy
Other Names:
  • Hysterectomy NOS
  • hysterectomy type
  • hysterectomy_type
Procedure: Biopsy Procedure
Undergo biopsy
Other Names:
  • Bx
  • BIOPSY_TYPE
  • Biopsy
Procedure: Curettage Procedure
Undergo curettage
Other Names:
  • Curettage
Experimental: Arm II (biopsy, curettage, progesterone, hysterectomy)
Patients undergo biopsy or curettage and then receive micronized progesterone PO QD beginning 21-24 days prior to SOC hysterectomy on study.
Procedure: Hysterectomy
Undergo hysterectomy
Other Names:
  • Hysterectomy NOS
  • hysterectomy type
  • hysterectomy_type
Procedure: Biopsy Procedure
Undergo biopsy
Other Names:
  • Bx
  • BIOPSY_TYPE
  • Biopsy
Procedure: Curettage Procedure
Undergo curettage
Other Names:
  • Curettage
Drug: Progesterone Only Hormone Replacement Therapy
Given PO
Other Names:
  • Progesterone only

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tissue response to progestin therapy
Time Frame: From the time of pre treatment diagnostic biopsy to the time of post treatment hysterectomy specimen
Will be determined by a change in the percentage in the expression of the proliferative marker Ki-67 comparing the pretreatment diagnostic biopsy to the posttreatment hysterectomy specimen. Immunohistochemical evaluation of Ki-67 protein expression will be determined as a continuous variable using the percent of cells staining positive in the nucleus
From the time of pre treatment diagnostic biopsy to the time of post treatment hysterectomy specimen

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

New Mexico Cancer Research Alliance

Collaborators

National Cancer Institute (NCI)
University of New Mexico Cancer Center

Investigators

  • Principal Investigator: Carolyn Y Muller, University of New Mexico Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2026

Primary Completion (Estimated)

June 30, 2030

Study Completion (Estimated)

June 30, 2031

Study Registration Dates

First Submitted

February 20, 2026

First Submitted That Met QC Criteria

February 20, 2026

First Posted (Actual)

February 27, 2026

Study Record Updates

Last Update Posted (Actual)

February 27, 2026

Last Update Submitted That Met QC Criteria

February 20, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INST UNM 2502 PRO-WINDOW (Other Identifier: University of New Mexico Cancer Center)
  • P30CA118100 (U.S. NIH Grant/Contract)
  • NCI-2025-06611 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • P01CA278735 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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