Trial Information

Clinical Trial Protocol for Therapeutic MRI-guided High Intensity Focused Ultrasound Ablation of Uterine Fibroids

Fibroids occur in 20-50% of women over 30 years of age, and with increasing size produce
pain, menorrhagia, pressure, bloating and urinary and bowel compression symptoms. Fibroids
may also cause infertility. Uterine leiomyomas are benign tumors originating from smooth
muscle cells of the uterus and occasionally the smooth muscle of uterine blood vessels.
Fibroids are estrogen dependent tumors ranging in size and number and can be found within
the myometrium(intramural), at the uterine periphery extending to the serosa (subserosal),
or pushing into the uterine cavity (submucosal). Symptomatic fibroids impact health and
well-being of the female including lost work hours and reduced quality of life.

Current medical treatments include invasive removal of the fibroid (hysterectomy,
myomectomy), drug therapy (GnRH analogues or progestin compounds) or treatments causing
necrosis of the fibroid tissue such as ablation (freezing or heating) or embolization. For
the relief of symptoms, women wishing to preserve the uterus may choose between invasive
procedures of myomectomy, Uterine Artery Embolization (UAE), ablation or cryotherapy. The
surgically invasive procedures require anesthesia, hospital stays, and long recovery
periods. HIFU may offer an alternative to the above mentioned surgically invasive
procedures.

In MRI-guided High Intensity Focused Ultrasound (HIFU), the ultrasound generated by the
transducer is focused into a small focal tissue volume at specific target locations. During
treatment, the beam of focused ultrasound energy penetrates through soft tissue and causes
localized high temperatures (55°C to 70°C) for a few seconds within the target producing
well defined regions of protein denaturation, irreversible cell damage, and coagulative
necrosis. The MRI system allows 3D planning, means of measuring the temperature increase
generated by HIFU, and the capability to quantifying the energy/dose delivered to the
treatment zone.

This study is a multi-center, single arm, non-randomized trial evaluating the safety,
technical effectiveness and volume treatment capabilities of the Philips MR-guided HIFU
system in the treatment of symptomatic uterine fibroid patients. Patients who have
symptomatic uterine fibroids, who are eligible according to the inclusion and exclusion
criteria and provide informed consent will be enrolled in this study. It is anticipated that
women will participate in the study for a 2month period to include the screening, HIFU
treatment and post treatment follow-up.

This clinical study is designed to confirm safety and demonstrate technical effectiveness of
the Philips HIFU system for Uterine Fibroid treatment. Safety will be primarily assessed by
evaluating minor complications and adverse events, and technical effectiveness will
primarily be assessed with MRI measurements. Specific primary and secondary endpoints are
detailed below.

The study will use a combination of three primary endpoints: MR imaging of ablated volumes
and minor complications/adverse events analysis to establish the safety and technical
effectiveness of the Philips MR-HIFU system. These endpoints will determine the trial
success.

The treatment capabilities and technical effectiveness of the Philips MR-guided HIFU system
will be assessed by (measurement type is noted in parentheses)

1. Comparing the actual MR-measured ablated volumes to MR thermal dose predicted volumes

Safety of the Philips MR-guided HIFU system will be demonstrated by

2. Evaluating any minor complications or adverse events that result from the MR-guided
HIFU treatment

3. Verifying with MR imaging that no unintended lesions are formed as a result of the
Treatment

Our hypothesis is that greater than 70% of fibroids will have concordance between
intended lesion volume and actual lesion volume while maintaining an acceptable safety
profile.

In addition, the following endpoints will be collected to supplement the primary
outcomes:

4. Pain and discomfort scores before, during and after treatment: These endpoints will be
recorded using a 10-point visual analog scale for pain 4-point scale for discomfort.

5. Return to Activity: This duration in days will be determined by the time after which
the patients return to work (i.e. days after leaving the hospital) or to the usual
activities for those not employed.

6. Length of Hospital Stay (LOS): This duration in hours will be measured from the time
the patient will arrive to the hospital until she will leave the hospital.

7. Quality of Life questionnaires: the SF-36(http://www.sf36.org/tools/SF36.shtml) and
UFS-QoL (which includes SSS)