Atypical Endometrial Hyperplasia, Endometrial Carcinoma
Conditions
Keywords
Well, Moderately, Differentiated
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.
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.
Interventions
DRUGMegestrol Acetate
Sponsors
NYU Langone Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Duration of Response | up to 4 years | For each patient, assessed every 12 weeks during treatment and every 6 months during follow-up. |
| Number of Women Who Became Pregnant | up to 3 years after the treatment for each patient | — |
Countries
United States
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 details
One patient withdrew before the start of the treatment; ony 30 patients started the treatment.
Participants by arm
| Arm | Count |
|---|---|
| Megestrol Acetate 80 mg (2 tablets) orally at breakfast, 80 mg at dinner for at least 12 weeks and up to 2 years. | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Patient Non Compliance | 2 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Megestrol Acetate |
|---|---|
| Age, Customized 18-24 years | 1 participants |
| Age, Customized 25-34 years | 12 participants |
| Age, Customized 35-44 years | 12 participants |
| Age, Customized 45-54 years | 4 participants |
| Age, Customized 55-64 yeras | 2 participants |
| Histological Diagnosis Atypical endometrial hyperplasia | 20 participants |
| Histological Diagnosis FIGO Grade 1 endometrioid carcinoma | 9 participants |
| Histological Diagnosis FIGO Grade 2 endometrioid carcinoma | 2 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Region of Enrollment United States | 31 participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 29 / 30 |
| serious Total, serious adverse events | 1 / 30 |
Outcome results
Primary
Best Pathologic Responses
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
Population: Patient who were able to complete at least one full course (12 weeks) of treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Megestrol Acetate | Best Pathologic Responses | Pathologic CR | 17 participants |
| Megestrol Acetate | Best Pathologic Responses | Unconfirmed CR | 4 participants |
| Megestrol Acetate | Best Pathologic Responses | PR | 6 participants |
| Megestrol Acetate | Best Pathologic Responses | SD | 1 participants |
| Megestrol Acetate | Best Pathologic Responses | PD | 2 participants |
Secondary
Duration of Response
For each patient, assessed every 12 weeks during treatment and every 6 months during follow-up.
Time frame: up to 4 years
Population: 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.
Secondary
Number of Women Who Became Pregnant
Time frame: up to 3 years after the treatment for each patient
Population: Only 7 participants in the trial pursued pregnancy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Megestrol Acetate | Number of Women Who Became Pregnant | 3 participants |
Secondary
Toxicity and Tolerability
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
Population: Any patient with at least one dose of treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Megestrol Acetate | Toxicity and Tolerability | Bloating | 4 participants |
| Megestrol Acetate | Toxicity and Tolerability | Insomnia | 4 participants |
| Megestrol Acetate | Toxicity and Tolerability | Fatigue | 6 participants |
| Megestrol Acetate | Toxicity and Tolerability | Weight gain | 9 participants |
| Megestrol Acetate | Toxicity and Tolerability | Mood alterations | 4 participants |
| Megestrol Acetate | Toxicity and Tolerability | Headache | 5 participants |
| Megestrol Acetate | Toxicity and Tolerability | Thromboembolic event | 0 participants |
| Megestrol Acetate | Toxicity and Tolerability | Carpal tunnel syndrome | 1 participants |
| Megestrol Acetate | Toxicity and Tolerability | Weakness | 1 participants |
| Megestrol Acetate | Toxicity and Tolerability | Vaginal Spotting | 6 participants |
| Megestrol Acetate | Toxicity and Tolerability | Vaginal Pain | 1 participants |
| Megestrol Acetate | Toxicity and Tolerability | Nausea | 6 participants |
| Megestrol Acetate | Toxicity and Tolerability | Abdominal Pain | 2 participants |
| Megestrol Acetate | Toxicity and Tolerability | Constipation | 3 participants |
| Megestrol Acetate | Toxicity and Tolerability | Increased Appetite | 4 participants |
| Megestrol Acetate | Toxicity and Tolerability | Depression | 3 participants |
| Grade 3 | Toxicity and Tolerability | Abdominal Pain | 0 participants |
| Grade 3 | Toxicity and Tolerability | Nausea | 0 participants |
| Grade 3 | Toxicity and Tolerability | Weakness | 0 participants |
| Grade 3 | Toxicity and Tolerability | Insomnia | 0 participants |
| Grade 3 | Toxicity and Tolerability | Bloating | 0 participants |
| Grade 3 | Toxicity and Tolerability | Fatigue | 0 participants |
| Grade 3 | Toxicity and Tolerability | Vaginal Spotting | 0 participants |
| Grade 3 | Toxicity and Tolerability | Weight gain | 0 participants |
| Grade 3 | Toxicity and Tolerability | Constipation | 0 participants |
| Grade 3 | Toxicity and Tolerability | Mood alterations | 0 participants |
| Grade 3 | Toxicity and Tolerability | Vaginal Pain | 0 participants |
| Grade 3 | Toxicity and Tolerability | Headache | 2 participants |
| Grade 3 | Toxicity and Tolerability | Depression | 0 participants |
| Grade 3 | Toxicity and Tolerability | Thromboembolic event | 1 participants |
| Grade 3 | Toxicity and Tolerability | Increased Appetite | 0 participants |
| Grade 3 | Toxicity and Tolerability | Carpal tunnel syndrome | 0 participants |