Atypical Endometrial HyperplasiaPhase 2NCT01943058
Megestrol Acetate or Levonorgestrel-Releasing Intrauterine System in Treating Patients With Atypical Endometrial Hyperplasia or Endometrial Cancer
A Phase 2 study testing megestrol acetate, levonorgestrel-releasing intrauterine system and laboratory biomarker analysis in people with Atypical Endometrial Hyperplasia and Endometrial Adenocarcinoma, run by University of Southern California.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 44 years, women only
- Conditions the study is for
- Atypical Endometrial Hyperplasia, Endometrial Adenocarcinoma, Recurrent Endometrial Carcinoma
- What is being tested?
- megestrol acetate, levonorgestrel-releasing intrauterine system and laboratory biomarker analysis
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Mar 2014to Oct 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 44 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
About this study
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)
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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:
- 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
- Atypical Endometrial Hyperplasia, Endometrial Adenocarcinoma, Recurrent Endometrial Carcinoma, Stage IA Endometrial Carcinoma, Stage IB Endometrial Carcinoma, Stage II Endometrial Carcinoma
- Being tested
- megestrol acetate, levonorgestrel-releasing intrauterine system, laboratory biomarker analysis, questionnaire administration
- Medical subject headings
- Endometrial Hyperplasia, Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
megestrol acetateDrug
Also called BDH 1298, Maygace, Megace, Megestil
Given PO
levonorgestrel-releasing intrauterine systemDevice
Also called Mirena
Given IUD
laboratory biomarker analysisOther
Correlative studies
questionnaire administrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Arm A (megestrol acetate) | Experimental | Patients receive megestrol acetate PO BID for up to 18 months in the absence of disease progression or unacceptable toxicity. Receives: Drug: megestrol acetate; Other: laboratory biomarker analysis; Other: questionnaire administration |
| Arm B (levonorgestrel-releasing IUS) | Experimental | Patients receive levonorgestrel-releasing IUS with continuous release for up to 18 months in the absence of disease progression or unacceptable toxicity. Receives: Device: levonorgestrel-releasing intrauterine system; Other: laboratory biomarker analysis; Other: questionnaire administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 6 months after completion of study treatment
Secondary outcomes (3)
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.
Measured: Baseline to up to 6 months after completion of study treatment
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.
Measured: Baseline to up to 6 months after completion of study treatment
Compliance
Can be evaluated using chi squared tests, logistic regression, or repeated measures ANOVA whenever appropriate.
Measured: Up to 6 months after completion of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2013 (estimated)
- Study startMar 2014
- Primary completionOct 2016 (estimated)
- Study completionOct 2017 (estimated)
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atypical Endometrial HyperplasiaStudies of the same condition, open and under way.
- More trials run by University of Southern CaliforniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Yvonne Lin-Liu, Principal investigator, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01943058
- Sponsor's protocol ID
- 5U-12-1
- Other IDs
- NCI-2013-01725, 5U-12-1, P30CA014089
- Status last verified
- Sep 2014
- First submitted
- 11 Sep 2013
- Last updated
- 10 Sep 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01943058
- Acronym / sponsor ID
- 5U-12-1
- Conditions
- Atypical Endometrial Hyperplasia, Endometrial Adenocarcinoma, Recurrent Endometrial Carcinoma, Stage IA Endometrial Carcinoma, Stage IB Endometrial Carcinoma, Stage II Endometrial Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Mar 2014
- Primary completion
- Oct 2016 (estimated)
- Study completion
- Oct 2017 (estimated)
- First posted
- 16 Sep 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A (megestrol acetate) | Experimental | Drug: megestrol acetate, Other: laboratory biomarker analysis, Other: questionnaire administrationPatients receive megestrol acetate PO BID for up to 18 months in the absence of disease progression or unacceptable toxicity. |
| Arm B (levonorgestrel-releasing IUS) | Experimental | Device: levonorgestrel-releasing intrauterine system, Other: laboratory biomarker analysis, Other: questionnaire administrationPatients receive levonorgestrel-releasing IUS with continuous release for up to 18 months in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 to 44 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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:
- Willing and able to consent for treatment with office endometrial biopsies every 3 months
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| megestrol acetateAlso: BDH 1298, Maygace, Megace, MegestilGiven PO | Drug | Arm A (megestrol acetate) |
| levonorgestrel-releasing intrauterine systemAlso: MirenaGiven IUD | Device | Arm B (levonorgestrel-releasing IUS) |
| laboratory biomarker analysisCorrelative studies | Other | Arm A (megestrol acetate), Arm B (levonorgestrel-releasing IUS) |
| questionnaire administrationAncillary studies | Other | Arm A (megestrol acetate), Arm B (levonorgestrel-releasing IUS) |
Primary outcome
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.
3 secondary outcomes
Change in weight
Time frame: Baseline to up to 6 months after completion of study treatment
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
Compliance
Time frame: Up to 6 months after completion of study treatment
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yvonne Lin-Liu principal investigator
University of Southern California
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing megestrol acetate, levonorgestrel-releasing intrauterine system and laboratory biomarker analysis in people with Atypical Endometrial Hyperplasia and Endometrial Adenocarcinoma, run by University of Southern California.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 10 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Histologic regression from endometrioid adenocarcinoma or complex atypical hyperplasia to benign endometrium (time frame: Up to 6 months after completion of study treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2014.