Study of Megestrol Acetate in Grade 2 Endometrioid Endometrial Cancer (MA-EEC)

The Effect of Megestrol Acetate on Grade 2 Endometrioid Endometrial Cancer in Patients Waiting for Definitive Surgery, a Prospective Trial

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.

Study Overview

• Status: Terminated
• Conditions: Endometrial Cancer
• Intervention / Treatment: Drug: Megestrol Acetate

Detailed Description

The incidence of endometrial cancer is increasing due to the rising rates of obesity. Further, the average age at onset is decreasing. As a result, there is a growing interest in fertility-sparing treatments, such as progesterone-based therapy. While the role of progestins for the conservative management of atypical hyperplasia and with Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) grade 1 endometrial endometrioid carcinomas (EEC), assigned on preoperative endometrial biopsy, is well established, there is limited clinical experience in patients FIGO grade 2 EECs (EEC2) for whom the current standard therapy is hysterectomy. However, there are case reports of successful progestin treatment of patients with preoperative biopsy EEC2, suggesting that progestin response mechanisms are functional in select EEC2s and that hormonal treatment may be a viable option if the responsive patients could be safely identified.

In this study, the investigators will prospectively recruit EEC2 patients for pre-operative progestin treatment. Participants will be given high-dose progestin from day of consent for a minimum of 21 days. This will allow investigators to generate a unique cohort of matched pre-progestin treatment biopsies and post-treatment surgical specimens for each participant. The investigators intend to analyze clinical, pathological and transcriptomic data of EEC2 that histologically respond to progestin therapy versus their counterparts that do not, with the goal of identifying candidate predictive biomarkers and clinical parameters that would supplement pathological screening of these lesions to better stratify patient classification to good and poor responders. Once good responders are successfully characterize, this will enable the investigators to identify patients with biopsy EEC2 that could be safely managed conservatively with oral progestin therapy. For young patients, who have not completed their family planning, this could mean the difference between undergoing a hysterectomy versus retaining their fertility.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Bojana Djordjevic, MD; Phone Number: (416) 480-6100 x5709; Email: bojana.djordjevic@sunnybrook.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 - Megestrol; 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; Megestrol acetate, 160 mg daily (two 40mg tablets twice a day), for a minimum of 18 days.; Other Names: Megace; MEGESTROL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlations between response to progestin and clinical, histological and transcriptomic pre-operative biomarkers that may impact therapy planning.	The secondary outcome answers whether there is a pre-treatment biomarker signature at baseline biopsy that can predict therapeutic response to progestin among grade 2 endometrioid endometrial cancer patients. To identify molecular correlates of treatment response transcriptional profiling of pre-treatment and post-treatment tissue specimens will be performed.	3 years

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: Ontario Institute for Cancer Research
• Investigators: Principal Investigator: Bojana Djordjevic, MD, SunnyBrook Health Sciences Centre; Principal Investigator: Danielle Vicus, MD, MSc, SunnyBrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2022
• Primary Completion (Actual): October 12, 2023
• Study Completion (Actual): October 12, 2023

Study Registration Dates

• First Submitted: April 10, 2022
• First Submitted That Met QC Criteria: April 10, 2022
• First Posted (Actual): April 18, 2022

Study Record Updates

• Last Update Posted (Estimated): November 3, 2023
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Predictive biomarkers; Endometrial endometrioid carcinomas; Oral progestin therapy; Fertility sparing treatment
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Endometrial Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Central Nervous System Stimulants; Appetite Stimulants; Megestrol; Megestrol Acetate
• Other Study ID Numbers: 4858

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No