Mirena® ± Metformin as Fertility-preserving Treatment for Young Asian Women With Early Endometrial Cancer

Primary objective To discover the efficacies of levonorgestrel-containing intrauterine device (LNG-IUS, Mirena®), with or without metformin, as fertility-preserving treatment for grade 1 endometrioid adenocarcinoma of endometrium, cT1aN0M0 with presumed no myometrial invasion on image study (MRI preferred).

Secondary objectives

1. To discover the morphological and molecular change in the endometrium tumor before and after treatment
2. To discover the effectiveness of adding oral progestin to subjects who show no good response to assigned
3. To compare (1) the systemic effects, including body weight change, neuropsychiatric alternation, GI disturbance, skin disorder, change in serum metabolic and hepatic markers between the two study patient groups; (2) The rate of long-term success defined as (a) sustained remission of >= 12 months starts from the histologic documentation of complete remission (b) rate of pregnancy and (c) alive baby delivery, based on time-to-event analysis.
4. Molecular markers and their expression before, during and after treatment, including progesterone B receptor, progesterone A receptor, estrogen receptor, Ki67, PTEN and its related markers, Bcl2 and its related markers and other developing markers. This is to discover prediction markers to medical treatment.

Study Overview

• Status: Unknown
• Conditions: Endometrial Cancer
• Intervention / Treatment: Drug: Metformin; Device: Mirena®

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Women <= 40 years old with histologic confirmed grade 1 endometrioid adenocarcinoma of the endometrium
2. Tumour is confirmed to the endometrial cavity with no evidence of metastasis on MRI and/or trans-vaginal ultrasonography
3. ECOG 0-1, adequate organ function, with fertility preserving need
4. Immunohistochemical study showed positive progesterone receptor and positive estrogen receptor in the endometrial tumour tissue
5. Serum CA 125 titre is within normal limit
6. Signed informed consent

Exclusion Criteria:

1. Women age > 40 years or endometrial cancer other than grade 1 endometrioid adenocarcinoma
2. Suspected lymph node metastasis or other metastasis appears in image study
3. Ovarian tumour in image study
4. Blurred junction between the endometrium and the myometrium on image study, with the impression that myometrial invasion of the endometrial tumour cannot be ruled out
5. Ultrasonographic study or MRI show obvious adenomyosis or ovarian endometriosis
6. Women who are contraindicated to receive study treatment because of intolerance to treatment agents, medical co-morbidity or other reason(s)
7. Women with history of or concurrent with malignancy other than skin basal cell carcinoma
8. Women who cannot participate regular follow-up

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mirena® + metformin; The enrolled patient is allocated to either LNG-IUS only or LNG-IUS + metformin by central randomization with study site allocation. A 90-100 days of continuous treatment before first histologic assessment of treatment response is required. The patient will receive endometrial curettage or hysteroscopic evaluation and resection of suspected lesion after 90-100 days of treatment. Patients with good response to assigned treatment will continue the treatment for another 90-100 days and second histologic assessment will be performed. Patients with poor response to assigned treatment at first assessment will receive additive oral progestin therapy, along with the assigned regimen(s) as, Oral progestin, either medroxyprogesterone acetate 500 mg daily or oral megestrol acetate 160 mg daily After a total of at least 6 months treatment period, the patient with good response at first assessment is suggested to keep the Mirena for maintenance until plan to get pregnant	Drug: Metformin; The enrolled patient is allocated to either LNG-IUS only or LNG-IUS + metformin by central randomization with study site allocation. A 90-100 days of continuous treatment before first histologic assessment of treatment response is required. The patient will receive endometrial curettage or hysteroscopic evaluation and resection of suspected lesion after 90-100 days of treatment. Patients with good response to assigned treatment will continue the treatment for another 90-100 days and second histologic assessment will be performed. Patients with poor response to assigned treatment at first assessment will receive additive oral progestin therapy, along with the assigned regimen(s) as, Oral progestin, either medroxyprogesterone acetate 500 mg daily or oral megestrol acetate 160 mg daily After a total of at least 6 months treatment period, the patient with good response at first assessment is suggested to keep the Mirena for maintenance until plan to get pregnant; Device: Mirena®
Active Comparator: Mirena®; The enrolled patient is allocated to either LNG-IUS only or LNG-IUS + metformin by central randomization with study site allocation. A 90-100 days of continuous treatment before first histologic assessment of treatment response is required. The patient will receive endometrial curettage or hysteroscopic evaluation and resection of suspected lesion after 90-100 days of treatment. Patients with good response to assigned treatment will continue the treatment for another 90-100 days and second histologic assessment will be performed. Patients with poor response to assigned treatment at first assessment will receive additive oral progestin therapy, along with the assigned regimen(s) as, Oral progestin, either medroxyprogesterone acetate 500 mg daily or oral megestrol acetate 160 mg daily After a total of at least 6 months treatment period, the patient with good response at first assessment is suggested to keep the Mirena for maintenance until plan to get pregnant	Device: Mirena®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the efficacies of levonorgestrel-containing intrauterine device (LNG-IUS, Mirena®), with or without metformin	the efficacies of levonorgestrel-containing intrauterine device (LNG-IUS, Mirena®), with or without metformin about 6 month

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Anticipated): March 1, 2018
• Study Completion (Anticipated): March 1, 2020

Study Registration Dates

• First Submitted: November 16, 2016
• First Submitted That Met QC Criteria: December 8, 2016
• First Posted (Estimate): December 13, 2016

Study Record Updates

• Last Update Posted (Estimate): December 13, 2016
• Last Update Submitted That Met QC Criteria: December 8, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Endometrial Cancer.Mirena®
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endometrial Neoplasms; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: CTC-184

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No