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

NCT07436793 | Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: INST UNM 2502 PRO-WINDOWNCI-2025-06611P01CA278735P30CA118100
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Endometrial Endometrioid Adenocarcinoma; Endometrial Hyperplasia

Outcome Measures

Primary Outcomes (1)

• Tissue response to progestin therapy

  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

Study Arms (2)

Arm I (biopsy, curettage, MPA, hysterectomy)

ACTIVE COMPARATOR

Patients undergo biopsy or curettage and then receive megestrol acetate PO BID 21-24 days prior to SOC hysterectomy on study.

Procedure: Biopsy Procedure; Procedure: Curettage Procedure; Procedure: Hysterectomy; Drug: Megestrol Acetate

Arm II (biopsy, curettage, progesterone, hysterectomy)

EXPERIMENTAL

Patients undergo biopsy or curettage and then receive micronized progesterone PO QD beginning 21-24 days prior to SOC hysterectomy on study.

Procedure: Biopsy Procedure; Procedure: Curettage Procedure; Procedure: Hysterectomy; Drug: Progesterone Only Hormone Replacement Therapy

Interventions

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Arm I (biopsy, curettage, MPA, hysterectomy); Arm II (biopsy, curettage, progesterone, hysterectomy)

Hysterectomy PROCEDURE

Undergo hysterectomy

Also known as: Hysterectomy NOS, hysterectomy type, hysterectomy_type

Arm I (biopsy, curettage, MPA, hysterectomy); Arm II (biopsy, curettage, progesterone, hysterectomy)

Megestrol Acetate DRUG

Given PO

Also known as: 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, Megace, Megestat, Megestil, Niagestin, Ovaban, Pallace, SC 10363, SC-10363

Arm I (biopsy, curettage, MPA, hysterectomy)

Progesterone Only Hormone Replacement Therapy DRUG

Given PO

Also known as: Progesterone only

Arm II (biopsy, curettage, progesterone, hysterectomy)

Curettage Procedure PROCEDURE

Undergo curettage

Also known as: Curettage

Arm I (biopsy, curettage, MPA, hysterectomy); Arm II (biopsy, curettage, progesterone, hysterectomy)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• New Mexico Cancer Research Alliance: lead
• University of New Mexico Cancer Center: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (4)

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

RECRUITING

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87106, United States

RECRUITING

University of Utah Sugarhouse Health Center

Salt Lake City, Utah, 84106, United States

NOT YET RECRUITING

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Endometrial Hyperplasia

Interventions

Biopsy; Curettage; Hysterectomy; Megestrol Acetate

Condition Hierarchy (Ancestors)

Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Gynecologic Surgical Procedures; Urogenital Surgical Procedures; Megestrol; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Carolyn Y Muller

  University of New Mexico Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2026
• First Posted: February 27, 2026
• Study Start: June 15, 2026
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): June 30, 2031
• Last Updated: July 2, 2026

Record last verified: 2026-06

Locations

US (4)