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

Primary Purpose

Atypical Endometrial Hyperplasia, Endometrial Adenocarcinoma, Recurrent Endometrial Carcinoma

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
megestrol acetate
levonorgestrel-releasing intrauterine system
laboratory biomarker analysis
questionnaire administration
Sponsored by
University of Southern California
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atypical Endometrial Hyperplasia

Eligibility Criteria

18 Years - 44 Years (Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Arm A (megestrol acetate)

    Arm B (levonorgestrel-releasing IUS)

    Arm Description

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

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

    Outcomes

    Primary Outcome Measures

    Histologic regression from endometrioid adenocarcinoma or complex atypical hyperplasia to benign endometrium
    Histologic regression will be dichotomized as a binary outcome variable, yes if patients have a confirmed histologic regression at the time of the scheduled biopsy, and no if the histologic regression is not observed regardless of compliance, lost-to-follow-up, or other issues. A contingency table and a bar plot will be used to show the histologic regression rate between the 2 arms. Two-group test of equivalence in proportions will be used to detect whether the histologic regression rate in Arm B is not significantly lower than that in Arm A.

    Secondary Outcome Measures

    Change in weight
    Weight gain will be recorded longitudinally at each 3-month clinic visit and body mass index (BMI) will be calculated and analyzed over time. Can be evaluated using chi squared tests, logistic regression, or repeated measures analysis of variance (ANOVA) whenever appropriate.
    Change in mood ascertained using the self-reported Beck Depression Inventory-Primary Care (BDI-PC)
    Can be evaluated using chi squared tests, logistic regression, or repeated measures ANOVA whenever appropriate.
    Compliance
    Can be evaluated using chi squared tests, logistic regression, or repeated measures ANOVA whenever appropriate.

    Full Information

    First Posted
    September 11, 2013
    Last Updated
    September 9, 2014
    Sponsor
    University of Southern California
    Collaborators
    National Cancer Institute (NCI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01943058
    Brief Title
    Megestrol Acetate or Levonorgestrel-Releasing Intrauterine System in Treating Patients With Atypical Endometrial Hyperplasia or Endometrial Cancer
    Official Title
    A Phase II Head-to-Head Comparison of Fertility-Sparing Approaches to Treat Complex Atypical Hyperplasia of the Edometrium: Megestrol Versus Levonorgestrel-Releasing Intrauterine System (LNG-IUS)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2014
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Lack of funding
    Study Start Date
    March 2014 (undefined)
    Primary Completion Date
    October 2016 (Anticipated)
    Study Completion Date
    October 2017 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University of Southern California
    Collaborators
    National Cancer Institute (NCI)

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    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
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    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

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Arm A (megestrol acetate)
    Arm Type
    Experimental
    Arm Description
    Patients receive megestrol acetate PO BID for up to 18 months in the absence of disease progression or unacceptable toxicity.
    Arm Title
    Arm B (levonorgestrel-releasing IUS)
    Arm Type
    Experimental
    Arm Description
    Patients receive levonorgestrel-releasing IUS with continuous release for up to 18 months in the absence of disease progression or unacceptable toxicity.
    Intervention Type
    Drug
    Intervention Name(s)
    megestrol acetate
    Other Intervention Name(s)
    BDH 1298, Maygace, Megace, Megestil, Niagestin
    Intervention Description
    Given PO
    Intervention Type
    Device
    Intervention Name(s)
    levonorgestrel-releasing intrauterine system
    Other Intervention Name(s)
    Mirena
    Intervention Description
    Given IUD
    Intervention Type
    Other
    Intervention Name(s)
    laboratory biomarker analysis
    Intervention Description
    Correlative studies
    Intervention Type
    Other
    Intervention Name(s)
    questionnaire administration
    Intervention Description
    Ancillary studies
    Primary Outcome Measure Information:
    Title
    Histologic regression from endometrioid adenocarcinoma or complex atypical hyperplasia to benign endometrium
    Description
    Histologic regression will be dichotomized as a binary outcome variable, yes if patients have a confirmed histologic regression at the time of the scheduled biopsy, and no if the histologic regression is not observed regardless of compliance, lost-to-follow-up, or other issues. A contingency table and a bar plot will be used to show the histologic regression rate between the 2 arms. Two-group test of equivalence in proportions will be used to detect whether the histologic regression rate in Arm B is not significantly lower than that in Arm A.
    Time Frame
    Up to 6 months after completion of study treatment
    Secondary Outcome Measure Information:
    Title
    Change in weight
    Description
    Weight gain will be recorded longitudinally at each 3-month clinic visit and body mass index (BMI) will be calculated and analyzed over time. Can be evaluated using chi squared tests, logistic regression, or repeated measures analysis of variance (ANOVA) whenever appropriate.
    Time Frame
    Baseline to up to 6 months after completion of study treatment
    Title
    Change in mood ascertained using the self-reported Beck Depression Inventory-Primary Care (BDI-PC)
    Description
    Can be evaluated using chi squared tests, logistic regression, or repeated measures ANOVA whenever appropriate.
    Time Frame
    Baseline to up to 6 months after completion of study treatment
    Title
    Compliance
    Description
    Can be evaluated using chi squared tests, logistic regression, or repeated measures ANOVA whenever appropriate.
    Time Frame
    Up to 6 months after completion of study treatment
    Other Pre-specified Outcome Measures:
    Title
    Change in levels of ER stress
    Description
    The changes in the biomarker levels will be examined using scatter plots or tables and paired tests such McNemar test, paired t-test or repeated measures ANOVA whenever appropriate.
    Time Frame
    Baseline up to 6 months after completion of study treatment
    Title
    Changes in levels of tumorigenic biomarkers
    Description
    The changes in the biomarker levels will be examined using scatter plots or tables and paired tests such McNemar test, paired t-test or repeated measures ANOVA whenever appropriate.
    Time Frame
    Baseline up to 6 months after completion of study treatment

    10. Eligibility

    Sex
    Female
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    44 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Yvonne Lin-Liu
    Organizational Affiliation
    University of Southern California
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

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

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