- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01943058
Megestrol Acetate or Levonorgestrel-Releasing Intrauterine System in Treating Patients With Atypical Endometrial Hyperplasia or Endometrial Cancer
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 Overview
Status
Conditions
- Atypical Endometrial Hyperplasia
- Recurrent Endometrial Carcinoma
- Endometrial Adenocarcinoma
- 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
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.
Study Type
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
Correlative studies
Ancillary studies
Given PO
Other Names:
|
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.
|
Correlative studies
Ancillary studies
Given IUD
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Up to 6 months after completion of study treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
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
|
Can be evaluated using chi squared tests, logistic regression, or repeated measures ANOVA whenever appropriate.
|
Baseline to up to 6 months after completion of study treatment
|
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.
|
Up to 6 months after completion of study treatment
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Baseline up to 6 months after completion of study treatment
|
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.
|
Baseline up to 6 months after completion of study treatment
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Yvonne Lin-Liu, University of Southern California
Study record dates
Study Major Dates
Study Start
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Uterine Neoplasms
- Genital Neoplasms, Female
- Uterine Diseases
- Carcinoma
- Hyperplasia
- Endometrial Hyperplasia
- Endometrial Neoplasms
- Physiological Effects of Drugs
- Antineoplastic Agents
- Antineoplastic Agents, Hormonal
- Contraceptive Agents, Hormonal
- Contraceptive Agents
- Reproductive Control Agents
- Contraceptives, Oral
- Contraceptive Agents, Female
- Contraceptives, Oral, Synthetic
- Contraceptives, Oral, Hormonal
- Central Nervous System Stimulants
- Appetite Stimulants
- Levonorgestrel
- Megestrol
- Megestrol Acetate
Other Study ID Numbers
- 5U-12-1 (OTHER: USC Norris Comprehensive Cancer Center)
- P30CA014089 (U.S. NIH Grant/Contract)
- NCI-2013-01725 (REGISTRY: CTRP (Clinical Trial Reporting Program))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Atypical Endometrial Hyperplasia
-
IRCCS Burlo GarofoloCompletedAtypical Endometrial Hyperplasia | Atypical Endometrial PolypsItaly
-
Zagazig UniversityCompletedAtypical Endometrial HyperplasiaEgypt
-
Fudan UniversityZhejiang Cancer Hospital; Shanghai 6th People's Hospital; Shanghai Changning...CompletedAtypical Endometrial HyperplasiaChina
-
Fudan UniversityTerminatedAtypical Endometrial HyperplasiaChina
-
West China Second University HospitalRecruitingAtypical Endometrial Hyperplasia | Endometrial CancerChina
-
Xiaojun ChenHuashan HospitalWithdrawnAtypical Endometrial Hyperplasia | Fertility Issues | Obese
-
Peking University People's HospitalPeking University; Beihang UniversityRecruitingAtypical Endometrial Hyperplasia | Endometrial Carcinoma Stage IChina
-
Krankenhaus Barmherzige Schwestern LinzCompletedEndometrial Cancer | Atypical HyperplasiaAustria
-
NYU Langone HealthCompletedAtypical Endometrial Hyperplasia | Endometrial CarcinomaUnited States
-
Peking University People's HospitalRecruitingAtypical Endometrial Hyperplasia | Endometrial Carcinoma Stage IChina
Clinical Trials on laboratory biomarker analysis
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletedProstate Cancer
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
National Cancer Institute (NCI)Recruiting
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)Not yet recruitingLynch Syndrome | Recurrent Uterine Corpus Carcinoma | Stage I Uterine Corpus Cancer | Stage II Uterine Corpus Cancer | Stage III Uterine Corpus Cancer | Stage IV Uterine Corpus CancerUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)Not yet recruitingRecurrent Uterine Corpus Carcinoma | Stage III Uterine Corpus Cancer | Stage IV Uterine Corpus CancerUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)RecruitingStage IIIA Ovarian Cancer | Stage IIIB Ovarian Cancer | Stage IIIC Ovarian Cancer | Stage IV Ovarian CancerUnited States
-
National Cancer Institute (NCI)Active, not recruitingMalignant NeoplasmUnited States
-
Ohio State University Comprehensive Cancer CenterActive, not recruitingLung Cancer | Radiation Toxicity | Adult Brain TumorUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Askin TumorUnited States, Canada, Puerto Rico, Australia, New Zealand, Switzerland
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed