Trial Information

A Phase II Study of the Levonorgestrel Intrauterine Device (Mirena) to Treat Complex Atypical Hyperplasia and Grade 1 Endometrioid Endometrial Carcinoma

The Levonorgestrel IUD:

The levonorgestrel IUD is a T-shaped birth control device that is made of flexible plastic.
It is designed to prevent pregnancy by releasing a hormone called levonorgestrel, which is a
type of progesterone. Progesterone is a common type of hormone that is used to prevent
pregnancy.

In this study, the levonorgestrel intrauterine device is being tested as a treatment for
hyperplasia and/or early-stage cancer of the lining of the uterus.

Study Surgery and IUD Placement:

If you are found to be eligible to take part in this study, you will have a surgical
procedure performed on Day 1 of the study (within 1 week after the screening tests). The
procedure is called dilation and curettage, and the purpose is to confirm your diagnosis.

First you will have a complete pelvic exam, and then the lining of your uterus will be
scraped in the operating room in order to remove a sample of tissue. The tissue sample will
be used to find out your exact diagnosis. Women who have previously undergone a dilation
and curettage (D&C) before for this diagnosis will not have to undergo a second D&C. The
Levonorgestrel IUD will then be placed in the clinic. During this surgery, to lower the risk
of pain during the procedure, you will receive general anesthesia. The cervix area may also
be numbed with anesthetic. You will be asked to sign a separate consent form for this
surgical procedure, and the procedure and its risks will be explained to you in more detail
at that time.

At the time of surgery, the levonorgestrel IUD will be inserted into your uterus, where it
will remain in place.

Study Visits:

After you have the IUD placed, you will return to the clinic for the following study visits.

About one (1) week after surgery, the study staff will review your surgery and pathology
results with you. If the results showed that you had a change in your diagnosis from
hyperplasia to early-stage cancer, you will be re-assessed for eligibility for our study.
If you are still eligible, you will have a chest x-ray and MRI of the abdomen. These scans
are being performed to check the status of the disease. If your pathology results show that
you have disease outside the uterus, you will be unable to take part in the study. The LIUD
can be removed in the operating room when you have surgery for removal of disease outside
the uterus. You may also have the LIUD removed in clinic.

About one (1) month after surgery, you will have a visit to check the placement of your
LIUD. This visit may be in our office or at your local doctor's office, whichever you
prefer. Placement of the LIUD will be checked first with a pelvic exam. In addition, you
may have an ultrasound of your uterus to confirm the location of your LIUD. If the IUD is
not in the correct location, it will be replaced at this visit.

At Months 3, 6, 9, and 12 after surgery, the following procedures will be performed:

- You will be asked about any side effects that you may be experiencing.

- You will have a a complete physical exam, including measurement of your vital signs.

- Your medical history will be recorded.

- You will have a biopsy of the lining of your uterus. To perform this biopsy, a small
plastic tube will be placed into your uterus. The tube will scrape off a tissue sample
from the lining of your uterus.

Biomarker Testing:

The leftover tissue after your study surgery will be tested for biomarkers (chemical
"markers" in the tissue that may be related to your response to the study drug,
levonorgestrel). This biomarker testing will also be performed on the tissue that is
leftover after your uterine lining biopsy at Month 3.

Length of Study Participation:

The first part of this study lasts 12 months, and the levonorgestrel IUD will remain in your
uterus during that time. If the disease gets worse or you experience intolerable side
effects at any time, you will be taken off study and the levonorgestrel IUD will be removed.
In that case, you would not need to return for the follow-up study visits described below.
Instead, you would visit your primary gynecologic oncologist (your regular doctor for the
disease), who will discuss with you the different treatment options for the disease.

At Month 12 of the study, you will be asked if you want to keep the levonorgestrel IUD in
place.

If you choose to have the levonorgestrel IUD removed at your Month 12 visit, you will be
considered "off study" after the Month 12 visit.

If you choose to keep the levonorgestrel IUD after Month 12, you will remain on study for as
long as the levonorgestrel IUD is still in place. Instead of visiting the study doctor, you
will visit your primary gynecologic oncologist after that. Anytime you have check-ups or
biopsies of the lining of your uterus as part of your routine medical care, as long as the
levonorgestrel IUD is still in place, the results of the check-ups or biopsies will be
shared with the study staff and will be used as part of this research study. You will
remain "on study" for as long as the levonorgestrel IUD is still in place. You may ask your
primary gynecologic oncologist to remove the IUD at any time.

This is an investigational study. The levonorgestrel IUD is commercially available and FDA
approved as a form of birth control. Its use for the treatment of cancer and hyperplasia is
experimental. At this time and for this purpose, it is only being used in research.

Up to 70 patients will take part in this multicenter study. Up to 50 will be enrolled at MD
Anderson.