Study of Megestrol Acetate in Grade 2 Endometrioid Endometrial Cancer

NCT05332483 | Terminated Phase 1 DMC

• 1 other identifier: 4858
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single centre, single arm, open label, preoperative window of opportunity study. Grade 2 endometrioid endometrial carcinoma patients awaiting surgery will be prospectively recruited to receive a pre-operative progestin therapy course. Therapy response will be histologically evaluated and correlated with clinical and molecular data by comparison of responders vs. non-responders pre- and post-treatment tumor samples.

Conditions

Endometrial Cancer

Keywords

Endometrial endometrioid carcinomas; Oral progestin therapy; Fertility sparing treatment; Predictive biomarkers

Outcome Measures

Primary Outcomes (1)

• Overall response rate of patients with biopsy grade 2 endometrioid endometrial cancer treated preoperatively with Megestrol acetate for a minimum of 21 days.

  Tumor response will be strictly histologically defined. Surgical specimens of each patient will be grossed in the pathology department as per standard of care. The degree of tumor response will be defined as follows: * Complete response: resolution of both cytologic atypia and architectural complexity to resemble non-tumorous endometrium. * Partial response: resolution of cytologic atypia and/or decrease in tumor grade (ie. From FIGO grade 2 to FIGO grade 1) * No response: persistence of the original lesion or progression to higher tumor grade.

  2 years

Secondary Outcomes (1)

• Correlations between response to progestin and clinical, histological and transcriptomic pre-operative biomarkers that may impact therapy planning.

  3 years

Study Arms (1)

Arm 1 - Megestrol

EXPERIMENTAL

All study participants will receive Megestrol acetate, 160 mg daily (two 40mg tablets twice a day), for a minimum of 18 days.

Drug: Megestrol Acetate

Interventions

Megestrol Acetate DRUG

Megestrol acetate, 160 mg daily (two 40mg tablets twice a day), for a minimum of 18 days.

Also known as: MEGESTROL, Megace

Arm 1 - Megestrol

Eligibility Criteria

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

You may qualify if:

• Adult female patient 18 years of age or older.
• Confirmed diagnosis of FIGO grade 2 endometrioid endometrial cancer on preoperative endometrial biopsy read by a pathologist with a subspecialty in gynecologic pathology.
• Stage 1 endometrioid endometrial cancer on preoperative endometrial biopsy.
• P53 wild type immunohistochemistry on preoperative endometrial biopsy.
• Patients eligible for primary staging surgery for definitive treatment for their cancer.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Required Initial Laboratory Values obtained within 3 days of enrolment following standard of care protocols: Absolute Neutrophil Count (ANC) ≥ 1,500/mm3; Platelet Count ≥ 100,000/mm3; eGFR ≥ 60 mL/min/1.73m2; Total Bilirubin ≤ 1.5 x upper limit of normal (ULN); AST / ALT ≤ 2.5 x upper limit of normal (ULN).
• Informed consent for this study is obtained and signed by the participant or have an acceptable Substitute Decision Maker (SDM) capable of signing the informed consent form on behalf of the participant.

You may not qualify if:

• Patients cannot be receiving systemic or hormonal therapy for treatment of the endometrial cancer.
• Prior radiation therapy for treatment of the endometrial cancer is not allowed.
• Stage 2 or 3 endometrioid endometrial cancer on preoperative endometrial biopsy.
• Abnormal p53 immunohistochemistry on preoperative endometrial biopsy.
• History of an allergic reaction to medroxyprogesterone acetate.
• History of venous thromboembolic event (including previous deep vein thrombosis or pulmonary embolism).
• Family history of venous thromboembolic event.
• Have a \>20 pack-year smoking history.
• Patients unwilling or unable to follow the study protocol schedule.

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• Ontario Institute for Cancer Research: collaborator

Study Sites (1)

Sunnybrook Health Sciences

Toronto, Ontario, M4N 3M5, Canada

Location

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

Megestrol Acetate; Megestrol

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Bojana Djordjevic, MD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

• Danielle Vicus, MD, MSc

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff gynecologic pathologist

Study Record Dates

• First Submitted: April 10, 2022
• First Posted: April 18, 2022
• Study Start: July 5, 2022
• Primary Completion: October 12, 2023
• Study Completion: October 12, 2023
• Last Updated: November 3, 2023

Record last verified: 2023-11

Locations

CA (1)