Management of Atypical Endometrial Hyperplasia and Endometrial Carcinoma Using Megestrol Acetate

• Sponsor: NYU Langone Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT00483327
• Collaborator: (none)
• Enrollment: 31
• Locations: 2
• Arm: 1
• Duration (Months): 76
• Patients Per Site: 15.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this trial is to study the efficacy, toxicity, and tolerability of a standard hormonal regimen of Megestrol Acetate (Megace) in the treatment of Atypical Endometrial Hyperplasia or well to moderately differentiated endometrial carcinoma.

Condition or Disease	Intervention/Treatment	Phase
Atypical Endometrial Hyperplasia; Endometrial Carcinoma	Drug: Megestrol Acetate	Phase 2

Detailed Description

The trial's objectives are to study the efficacy, defined as complete pathologic resolution of disease, of a standard hormonal regimen with the progestin Megace for the treatment of atypical endometrial hyperplasia or well or moderately differentiated endometrial carcinoma in women desiring conservative medical management of these conditions in the Women's Cancer Program at the NYU School of Medicine and at the Bellevue Gynecologic Oncology clinics.

The major endpoint is pathologic complete response (pCR). For the purposes of this study, patients will be reevaluated for response every 12 weeks until complete response. Response will be assessed within 4 weeks of completion of 12 weeks of Megace, by endometrial biopsy or dilation and curettage (D&C)/hysteroscopy. An endometrial biopsy is sufficient to document progressive, stable disease or partial response. A D&C is necessary to confirm complete response.

Patients whose disease has completely responded will discontinue treatment and be encouraged to pursue fertility. Those not desiring immediate fertility will be placed on low dose oral contraceptive pills for at least 6 months. Patients who have had either a partial response or stable disease will be recounseled and offered continued medical management or surgical therapy. Patients whose disease has progressed will be offered definitive surgical management. Those patients declining surgery will still be followed on study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prospective Trial of Conservative Management of Atypical Endometrial Hyperplasia and Well to Moderately Differentiated Endometrial Carcinoma Using Megestrol Acetate
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Megestrol Acetate 80 mg (2 tablets) orally at breakfast, 80 mg at dinner for at least 12 weeks and up to 2 years.	Drug: Megestrol Acetate; Other Names: Megace

Outcome Measures

Primary Outcome Measures

1. Best Pathologic Responses [up to 24 months]

   Patients are evaluated every 12 weeks while on treatment. The response is evaluated by endometrial biopsy or dilation and curettage (D&C)/hysteroscopy. Complete response (CR) is defined as endometrial sampling is read as normal or proliferative endometrium. Partial response (PR) is defined as the biopsy sample has changed on the endometrial evaluation scale by at least one level towards normal. Stable disease (SD) is defined as no change in pathology between the index and follow-up sample. Progressive disease (PD) is defined the follow-up sample has changed towards neoplasia on the endometrial evaluation scale by at least one level or imaging is concerning for myometrial invasion or extrauterine disease such that conservative management is no longer medically appropriate.

Secondary Outcome Measures

1. Toxicity and Tolerability [up to 36 months]

   Patients with adverse events (AEs) which were possibly, probably, or definitely related to the treatment. AEs were evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) 3.

2. Duration of Response [up to 4 years]

   For each patient, assessed every 12 weeks during treatment and every 6 months during follow-up.

3. Number of Women Who Became Pregnant [up to 3 years after the treatment for each patient]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Women with a diagnosis of atypical endometrial hyperplasia or G1 or G2 endometrial carcinoma confirmed by an New York University (NYU) pathologist desiring medical management will be eligible. The diagnosis may be obtained either by endometrial biopsy or D&C. If diagnosis has been made outside of NYU, slides must be available for review.

• Age > = 18 years.

• Life expectancy of greater than 12 months.

• Gynecologic Oncology Group (GOG) performance status score of 0, 1 or 2

• Patients must have normal organ and marrow function as defined below:

• leukocytes > = 3,000/mcL

• platelets > = 100,000/mcL

• total bilirubin within normal institutional limits

• AST(SGOT)/ALT(SGPT) no greater than 2.5 X institutional upper limit of Normal

• glucose < 200 mg/dl

• creatinine within normal institutional limits OR

• creatinine clearance > = 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal

• Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of Megace will be determined following review of their case by the Principal Investigator.

• The effects of Megace on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because Megace is known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Patients with a histological diagnosis of clear cell, papillary serous or poorly differentiated (G3) endometrial carcinoma.

• Patients with cancer have an MRI showing evidence of extrauterine spread or myometrial invasion.

• Presence of US findings suspicious for ovarian malignancy, unclear endometrial primary or recurrent endometrial cancer.

• Patients receiving other investigational agents.

• Patients with a history of a previous thrombotic event, known thrombophilic condition or poorly controlled diabetes.

• Patients with a history of breast cancer or other hormonally responsive malignancy.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• Pregnant women are excluded from this study because Megace has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Megace, breastfeeding should be discontinued if the mother is treated with Megace.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bellevue Hospital	New York	New York	United States	10016
2	NYU Cancer Center	New York	New York	United States	10016

Sponsors and Collaborators

• NYU Langone Health

Investigators

• Principal Investigator: Stephanie V Blank, M.D., New York University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT00483327
• Other Study ID Numbers: 06-685
• First Posted: Jun 7, 2007
• Last Update Posted: Apr 4, 2018
• Last Verified: Mar 1, 2018

• Keywords provided by NYU Langone Health: Well; Moderately; Differentiated
• Additional relevant MeSH terms: Carcinoma; Endometrial Neoplasms; Endometrial Hyperplasia; Hyperplasia; Megestrol; Megestrol Acetate

Study Results

Participant Flow

Recruitment Details	From May 2007 to April 2012, total 31 patients were recruited to the study from New York University medical center and its affiliated hospitals.
Pre-assignment Detail	One patient withdrew before the start of the treatment; ony 30 patients started the treatment.

Arm/Group Title	Megestrol Acetate
Arm/Group Description	80 mg (2 tablets) orally at breakfast, 80 mg at dinner for at least 12 weeks and up to 2 years.
Period Title: Overall Study
STARTED	30
COMPLETED	20
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	Megestrol Acetate
Arm/Group Description	80 mg (2 tablets) orally at breakfast, 80 mg at dinner for at least 12 weeks and up to 2 years.
Overall Participants	31
Age, Customized (participants) [Number]
18-24 years	1 3.2%
25-34 years	12 38.7%
35-44 years	12 38.7%
45-54 years	4 12.9%
55-64 yeras	2 6.5%
Sex: Female, Male (Count of Participants)
Female	31 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	6 19.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 12.9%
White	18 58.1%
More than one race	0 0%
Unknown or Not Reported	3 9.7%
Region of Enrollment (participants) [Number]
United States	31 100%
Histological Diagnosis (participants) [Number]
Atypical endometrial hyperplasia	20 64.5%
FIGO Grade 1 endometrioid carcinoma	9 29%
FIGO Grade 2 endometrioid carcinoma	2 6.5%

Outcome Measures

1. Primary Outcome

Title	Best Pathologic Responses
Description	Patients are evaluated every 12 weeks while on treatment. The response is evaluated by endometrial biopsy or dilation and curettage (D&C)/hysteroscopy. Complete response (CR) is defined as endometrial sampling is read as normal or proliferative endometrium. Partial response (PR) is defined as the biopsy sample has changed on the endometrial evaluation scale by at least one level towards normal. Stable disease (SD) is defined as no change in pathology between the index and follow-up sample. Progressive disease (PD) is defined the follow-up sample has changed towards neoplasia on the endometrial evaluation scale by at least one level or imaging is concerning for myometrial invasion or extrauterine disease such that conservative management is no longer medically appropriate.
Time Frame	up to 24 months

Outcome Measure Data

Analysis Population Description

Patient who were able to complete at least one full course (12 weeks) of treatment

Arm/Group Title	Megestrol Acetate
Arm/Group Description	80 mg (2 tablets) orally at breakfast, 80 mg at dinner for at least 12 weeks and up to 2 years.
Measure Participants	30
Pathologic CR	17 54.8%
Unconfirmed CR	4 12.9%
PR	6 19.4%
SD	1 3.2%
PD	2 6.5%

2. Secondary Outcome

Title	Toxicity and Tolerability
Description	Patients with adverse events (AEs) which were possibly, probably, or definitely related to the treatment. AEs were evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) 3.
Time Frame	up to 36 months

Outcome Measure Data

Analysis Population Description

Any patient with at least one dose of treatment.

Arm/Group Title	Grade 1 or 2	Grade 3
Arm/Group Description	80 mg (2 tablets) orally at breakfast, 80 mg at dinner for at least 12 weeks and up to 2 years.	80 mg (2 tablets) orally at breakfast, 80 mg at dinner for at least 12 weeks and up to 2 years.
Measure Participants	30	30
Weight gain	9 29%	0 NaN
Mood alterations	4 12.9%	0 NaN
Headache	5 16.1%	2 NaN
Thromboembolic event	0 0%	1 NaN
Carpal tunnel syndrome	1 3.2%	0 NaN
Weakness	1 3.2%	0 NaN
Vaginal Spotting	6 19.4%	0 NaN
Vaginal Pain	1 3.2%	0 NaN
Nausea	6 19.4%	0 NaN
Insomnia	4 12.9%	0 NaN
Fatigue	6 19.4%	0 NaN
Abdominal Pain	2 6.5%	0 NaN
Constipation	3 9.7%	0 NaN
Increased Appetite	4 12.9%	0 NaN
Depression	3 9.7%	0 NaN
Bloating	4 12.9%	0 NaN

3. Secondary Outcome

Title	Duration of Response
Description	For each patient, assessed every 12 weeks during treatment and every 6 months during follow-up.
Time Frame	up to 4 years

Outcome Measure Data

Analysis Population Description

The original PI for this study is no longer at our institution. Additionally, co-investigator has stated that this data was not collected and therefore not analyzed. This information is not available for reporting as it does not exist.

Arm/Group Title	Grade 1 or 2	Grade 3
Arm/Group Description	80 mg (2 tablets) orally at breakfast, 80 mg at dinner for at least 12 weeks and up to 2 years.	80 mg (2 tablets) orally at breakfast, 80 mg at dinner for at least 12 weeks and up to 2 years.
Measure Participants	0	0

4. Secondary Outcome

Title	Number of Women Who Became Pregnant
Time Frame	up to 3 years after the treatment for each patient

Outcome Measure Data

Analysis Population Description

Only 7 participants in the trial pursued pregnancy.

Arm/Group Title	Megestrol Acetate
Arm/Group Description	80 mg (2 tablets) orally at breakfast, 80 mg at dinner for at least 12 weeks and up to 2 years.
Measure Participants	7
Number [participants]	3 9.7%

Adverse Events

Adverse Event Reporting Description	All the adverse events are reported here regardless of attribution.
Arm/Group Title	Megestrol Acetate
Arm/Group Description	80 mg (2 tablets) orally at breakfast, 80 mg at dinner for at least 12 weeks and up to 2 years.
All Cause Mortality
	Megestrol Acetate
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Megestrol Acetate
	Affected / at Risk (%)	# Events
Total	1/30 (3.3%)
Vascular disorders
Thrombosis/thrombus/embolism	1/30 (3.3%)
Other (Not Including Serious) Adverse Events
	Megestrol Acetate
	Affected / at Risk (%)	# Events
Total	29/30 (96.7%)
Blood and lymphatic system disorders
Edema: head and neck:	1/30 (3.3%)
Cardiac disorders
Hypertension	2/30 (6.7%)
Hypotension	1/30 (3.3%)
Endocrine disorders
Hot flashes/flushes	3/30 (10%)
Gastrointestinal disorders
Anorexia	1/30 (3.3%)
Constipation	3/30 (10%)
Diarrhea	1/30 (3.3%)
Distension/bloating, abdominal	5/30 (16.7%)
Dysphagia (difficulty swallowing)	1/30 (3.3%)
Flatulence	1/30 (3.3%)
Gastrointestinal - Other: Increased Appetite	4/30 (13.3%)
Nausea	7/30 (23.3%)
Pain: Abdomen NOS	7/30 (23.3%)
Vomiting	1/30 (3.3%)
pain: stomach	1/30 (3.3%)
General disorders
Constitutional Symptoms - Other: thirst	3/30 (10%)
Fatigue (asthenia, lethargy, malaise)	7/30 (23.3%)
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	1/30 (3.3%)
Flu-like syndrome	1/30 (3.3%)
Insomnia	4/30 (13.3%)
Odor (patient odor)	1/30 (3.3%)
Pain - Other: side of body	2/30 (6.7%)
Rigors/chills	1/30 (3.3%)
Sweating (diaphoresis)	2/30 (6.7%)
Weight gain	9/30 (30%)
Pain: Pain NOS	1/30 (3.3%)
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	1/30 (3.3%)
Urticaria (hives, welts, wheals)	1/30 (3.3%)
Injury, poisoning and procedural complications
Hemorrhage/bleeding associated with surgery, intra-operative or postoperative	1/30 (3.3%)
Metabolism and nutrition disorders
Glucose, serum-low (hypoglycemia)	1/30 (3.3%)
Proteinuria	1/30 (3.3%)
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy): Whole body/generalized	1/30 (3.3%)
Musculoskeletal/Soft Tissue - Other: Spasm	1/30 (3.3%)
Pain: Back	3/30 (10%)
Pain: Extremity-limb	1/30 (3.3%)
Pain: Muscle	1/30 (3.3%)
Nervous system disorders
Confusion	1/30 (3.3%)
Dizziness	1/30 (3.3%)
Memory impairment	1/30 (3.3%)
Mood alteration: Agitation	1/30 (3.3%)
Mood alteration: Anxiety	3/30 (10%)
Mood alteration: Depression	5/30 (16.7%)
Neuropathy: cranial: CN V Motor-jaw muscles; Sensory-facial	1/30 (3.3%)
Neuropathy: sensory	3/30 (10%)
Pain: Head/headache	7/30 (23.3%)
Pain: Neuralgia/peripheral nerve	1/30 (3.3%)
Renal and urinary disorders
Cystitis	1/30 (3.3%)
Renal/Genitourinary - Other: Burning With Urination	1/30 (3.3%)
Urinary frequency/urgency	4/30 (13.3%)
Reproductive system and breast disorders
Hemorrhage, GU: Vagina	17/30 (56.7%)
Irregular menses (change from baseline)	1/30 (3.3%)
Libido	1/30 (3.3%)
Pain: Pelvis	1/30 (3.3%)
Pain: Vagina	1/30 (3.3%)
Vaginal discharge (non-infectious)	2/30 (6.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	4/30 (13.3%)
Pain: Chest/thorax NOS	2/30 (6.7%)
Pain: Pleura	1/30 (3.3%)
Pain: Throat/pharynx/larynx	2/30 (6.7%)
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other: skin peeling	1/30 (3.3%)
Dry skin	2/30 (6.7%)
Flushing	1/30 (3.3%)
Pruritus/itching	1/30 (3.3%)
Rash/desquamation	1/30 (3.3%)
Rash: acne/acneiform	1/30 (3.3%)
Dermatology/Skin - Other: blister	1/30 (3.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.