Megestrol Acetate or Levonorgestrel-Releasing Intrauterine System in Treating Patients With Atypical Endometrial Hyperplasia or Endometrial Cancer

NCT ID: NCT01943058

Last Updated: 2014-09-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2014-03-31

Study Completion Date

2017-10-31

Brief Summary

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This randomized phase II trial studies how well megestrol acetate or levonorgestrel-releasing intrauterine system works in treating patients with atypical endometrial hyperplasia or endometrial cancer. Progesterone can cause the growth of endometrial cancer cells. Hormone therapy using megestrol acetate or levonorgestrel-releasing intrauterine system may fight endometrial cancer by lowering the amount of progesterone the body makes. It is not yet known whether megestrol acetate is more effective than levonorgestrel-releasing intrauterine system in treating atypical endometrial hyperplasia or endometrial cancer.

Detailed Description

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PRIMARY OBJECTIVES:

I. To determine if the levonorgestrel-releasing intrauterine system (IUS) results in histologic regression of the endometrial lesion (complex atypical hyperplasia \[CAH\] and grade 1 endometrial cancer \[EC\]) comparable to that achieved with oral megestrol (megestrol acetate).

SECONDARY OBJECTIVES:

I. To compare both the side effect profiles, such as weight gain and mood changes as well as compliance with assigned treatment between the 2 treatment arms.

TERTIARY OBJECTIVES:

I. To describe fertility-related outcomes, ovulation, menstrual pattern and fertility abnormalities determined during usual workup (e.g., semen analysis), pregnancy and delivery within 18-months of treatment.

II. To characterize the incidence of endocrine comorbidities (e.g., hypothyroidism, polycystic ovarian syndrome, and diabetes).

III. To characterize the association of levels of endoplasmic reticular (ER) stress and protein kinase B (Akt)-activation in endometrial samples with clinicopathologic-response to Progestin (therapeutic progesterone) therapy.

OUTLINE:

Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive megestrol acetate orally (PO) twice daily (BID) for up to 18 months in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive levonorgestrel-releasing IUS with continuous release for up to 18 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 3 and 6 months.

Conditions

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Atypical Endometrial Hyperplasia Endometrial Adenocarcinoma Recurrent Endometrial Carcinoma Stage IA Endometrial Carcinoma Stage IB Endometrial Carcinoma Stage II Endometrial Carcinoma Stage IIIA Endometrial Carcinoma Stage IIIB Endometrial Carcinoma Stage IIIC Endometrial Carcinoma Stage IVA Endometrial Carcinoma Stage IVB Endometrial Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A (megestrol acetate)

Patients receive megestrol acetate PO BID for up to 18 months in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

megestrol acetate

Intervention Type DRUG

Given PO

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

questionnaire administration

Intervention Type OTHER

Ancillary studies

Arm B (levonorgestrel-releasing IUS)

Patients receive levonorgestrel-releasing IUS with continuous release for up to 18 months in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

levonorgestrel-releasing intrauterine system

Intervention Type DEVICE

Given IUD

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

questionnaire administration

Intervention Type OTHER

Ancillary studies

Interventions

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megestrol acetate

Given PO

Intervention Type DRUG

levonorgestrel-releasing intrauterine system

Given IUD

Intervention Type DEVICE

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

questionnaire administration

Ancillary studies

Intervention Type OTHER

Other Intervention Names

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BDH 1298 Maygace Megace Megestil Niagestin Mirena

Eligibility Criteria

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Inclusion Criteria

* A histologic diagnosis of complex atypical hyperplasia or grade 1 endometrioid adenocarcinoma of the endometrium diagnoses within 3 months of study enrollment who strongly desire to maintain fertility
* A diagnosis of endometrioid adenocarcinoma will undergo a magnetic resonance imaging (MRI) scan of the pelvis to rule out deep (\> 50%) myometrial invasion and extrauterine metastases
* A negative urine or serum pregnancy test at the time of enrollment
* 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, for the duration of study participation, and for 90 days following completion of therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; a female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
* Willing and able to consent for treatment with office endometrial biopsies every 3 months
* Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria

* A diagnosis of grade 1 endometrioid adenocarcinoma of the endometrium who does not wish to maintain fertility
* MRI evidence of deep myometrial and/or extrauterine spread
* Congenital or other structural uterine or tubal abnormality
* An acute pelvic inflammatory disease or medical conditions, such as, but not limited to acquired immunodeficiency syndrome (AIDS) and chronic immunosuppression, that may be associated with an increased susceptibility to infections
* Current diagnosis of breast cancer or any other cancer
* Currently pregnant or breastfeeding
* Thromboembolic disease, deep vein thrombosis, hypercoagulable state
Minimum Eligible Age

18 Years

Maximum Eligible Age

44 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

University of Southern California

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Yvonne Lin-Liu

Role: PRINCIPAL_INVESTIGATOR

University of Southern California

Other Identifiers

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NCI-2013-01725

Identifier Type: REGISTRY

Identifier Source: secondary_id

5U-12-1

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA014089

Identifier Type: NIH

Identifier Source: secondary_id

View Link

5U-12-1

Identifier Type: -

Identifier Source: org_study_id

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