Clinical trial NCT01943058: 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
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: 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
Lead sponsor: University of Southern California
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2013-09-16
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 44
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Histologic regression from endometrioid adenocarcinoma or complex atypical hyperplasia to benign endometrium
timeFrame: Up to 6 months after completion of study treatment
Secondary outcomes:
measure: Change in weight
timeFrame: Baseline to up to 6 months after completion of study treatment
measure: Change in mood ascertained using the self-reported Beck Depression Inventory-Primary Care (BDI-PC)
timeFrame: Baseline to up to 6 months after completion of study treatment
measure: Compliance
timeFrame: Up to 6 months after completion of study treatment
Other outcomes:
measure: Change in levels of ER stress
timeFrame: Baseline up to 6 months after completion of study treatment
measure: Changes in levels of tumorigenic biomarkers
timeFrame: Baseline up to 6 months after completion of study treatment
Locations:
Study officials:
affiliation: University of Southern California
name: Yvonne Lin-Liu
role: PRINCIPAL_INVESTIGATOR
References: