Endometrial CancerPhase 1MA-EECNCT05332483
Study of Megestrol Acetate in Grade 2 Endometrioid Endometrial Cancer
A Phase 1 study testing Megestrol Acetate in people with Endometrial Cancer, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Endometrial Cancer
- What is being tested?
- Megestrol Acetate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteCanada
- Study dates
- 5 Jul 2022to 12 Oct 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- Family history of venous thromboembolic event.
- Have a >20 pack-year smoking history.
- Patients unwilling or unable to follow the study protocol schedule.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Endometrial Cancer
- Being tested
- Megestrol Acetate
- Keywords
- Endometrial endometrioid carcinomas, Oral progestin therapy, Fertility sparing treatment, Predictive biomarkers
- Medical subject headings
- Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Megestrol AcetateDrug
Also called MEGESTROL, Megace
Megestrol acetate, 160 mg daily (two 40mg tablets twice a day), for a minimum of 18 days.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Megestrol Acetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years
Secondary outcomes (1)
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.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2022
- Study start5 Jul 2022
- Primary completion12 Oct 2023
- Study completion12 Oct 2023
Why it stopped: Slow enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Endometrial CancerStudies of the same condition, open and under way.
- More trials run by Sunnybrook Health Sciences CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Collaborators
- Ontario Institute for Cancer Research
- Responsible party
- Principal investigator, Bojana Djordjevic, Sunnybrook Health Sciences Centre
- Investigators
- Bojana Djordjevic, MD, Principal investigator, Sunnybrook Health Sciences CentreDanielle Vicus, MD, MSc, Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05332483
- Sponsor's protocol ID
- 4858
- Acronym
- MA-EEC
- Status last verified
- Nov 2023
- First submitted
- 10 Apr 2022
- Last updated
- 3 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Megestrol Acetate on Grade 2 Endometrioid Endometrial Cancer in Patients Waiting for Definitive Surgery, a Prospective Trial
- ClinicalTrials.gov ID
- NCT05332483
- Acronym / sponsor ID
- MA-EEC / 4858
- Conditions
- Endometrial Cancer
- Keywords
- Endometrial endometrioid carcinomas, Oral progestin therapy, Fertility sparing treatment, Predictive biomarkers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow enrollment
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Collaborators
- Ontario Institute for Cancer Research
- Study start
- 5 Jul 2022 (actual)
- Primary completion
- 12 Oct 2023 (actual)
- Study completion
- 12 Oct 2023 (actual)
- First posted
- 18 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1 - Megestrol | Experimental | Drug: Megestrol AcetateAll study participants will receive Megestrol acetate, 160 mg daily (two 40mg tablets twice a day), for a minimum of 18 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Megestrol AcetateAlso: MEGESTROL, MegaceMegestrol acetate, 160 mg daily (two 40mg tablets twice a day), for a minimum of 18 days. | Drug | Arm 1 - Megestrol |
Primary outcome
Overall response rate of patients with biopsy grade 2 endometrioid endometrial cancer treated preoperatively with Megestrol acetate for a minimum of 21 days.
Time frame: 2 years
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.
1 secondary outcome
Correlations between response to progestin and clinical, histological and transcriptomic pre-operative biomarkers that may impact therapy planning.
Time frame: 3 years
Results and safety
The study was stopped early (reason given: Slow enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bojana Djordjevic, MD principal investigator
Sunnybrook Health Sciences Centre
Danielle Vicus, MD, MSc principal investigator
Sunnybrook Health Sciences Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Megestrol Acetate in people with Endometrial Cancer, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Slow enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate of patients with biopsy grade 2 endometrioid endometrial cancer treated preoperatively with Megestrol acetate for a minimum of 21 days. (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2023.