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

This study has been withdrawn prior to enrollment.
(Lack of funding)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01943058
First Posted: September 16, 2013
Last Update Posted: September 10, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Southern California
  Purpose
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.

Condition Intervention Phase
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 Drug: megestrol acetate Device: levonorgestrel-releasing intrauterine system Other: laboratory biomarker analysis Other: questionnaire administration Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by University of Southern California:

Primary Outcome Measures:
  • Histologic regression from endometrioid adenocarcinoma or complex atypical hyperplasia to benign endometrium [ Time Frame: Up to 6 months after completion of study treatment ]
    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 [ Time Frame: Baseline to up to 6 months after completion of study treatment ]
    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) [ Time Frame: Baseline to up to 6 months after completion of study treatment ]
    Can be evaluated using chi squared tests, logistic regression, or repeated measures ANOVA whenever appropriate.

  • Compliance [ Time Frame: Up to 6 months after completion of study treatment ]
    Can be evaluated using chi squared tests, logistic regression, or repeated measures ANOVA whenever appropriate.


Other Outcome Measures:
  • Change in levels of ER stress [ Time Frame: Baseline up to 6 months after completion of study treatment ]
    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.

  • Changes in levels of tumorigenic biomarkers [ Time Frame: Baseline up to 6 months after completion of study treatment ]
    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.


Enrollment: 0
Study Start Date: March 2014
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (megestrol acetate)
Patients receive megestrol acetate PO BID for up to 18 months in the absence of disease progression or unacceptable toxicity.
Drug: megestrol acetate
Given PO
Other Names:
  • BDH 1298
  • Maygace
  • Megace
  • Megestil
  • Niagestin
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Experimental: 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.
Device: levonorgestrel-releasing intrauterine system
Given IUD
Other Name: Mirena
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 44 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01943058


Sponsors and Collaborators
University of Southern California
National Cancer Institute (NCI)
Investigators
Principal Investigator: Yvonne Lin-Liu University of Southern California
  More Information

Responsible Party: University of Southern California
ClinicalTrials.gov Identifier: NCT01943058     History of Changes
Other Study ID Numbers: 5U-12-1
NCI-2013-01725 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
5U-12-1 ( Other Identifier: USC Norris Comprehensive Cancer Center )
P30CA014089 ( U.S. NIH Grant/Contract )
First Submitted: September 11, 2013
First Posted: September 16, 2013
Last Update Posted: September 10, 2014
Last Verified: September 2014

Additional relevant MeSH terms:
Carcinoma
Adenocarcinoma
Hyperplasia
Endometrial Neoplasms
Endometrial Hyperplasia
Uterine Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Pathologic Processes
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female
Levonorgestrel
Megestrol
Megestrol Acetate
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Appetite Stimulants
Central Nervous System Stimulants