Therapeutic Magnetic Resonance Imaging (MRI)-Guided High Intensity Focused Ultrasound (HIFU) Ablation of Uterine Fibroids

Therapeutic Magnetic Resonance Imaging (MRI)-Guided High Intensity Focused Ultrasound (HIFU) Ablation of Uterine Fibroids

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

This study is to confirm the safety and technical effectiveness of MRI guided High Intensity Focused Ultrasound (HIFU) in ablating uterine tissue associated with symptomatic leiomyomas. The importance of this therapy is that it offers a non-invasive, uterine sparing procedure for the treatment of uterine fibroids in pre- and peri- menopausal women. MRI guided high intensity focused ultrasound uses ultrasound to heat and thermally ablate fibroid tissue. The MRI system identifies the ultrasound path and monitors heat rise in the fibroid tissue. The goal of the study is to show treatment safety and technical effectiveness. MR-guided HIFU will be performed in patients who pass inclusion/exclusion criteria. Safety, quality of life, and imaging endpoints will be evaluated in all study patients. The goal of this study is to demonstrate that: The safety profile is acceptable (safety) Actual MR-HIFU ablated volumes (as measured with contrast enhanced MRI) match the intended volumes (technical effectiveness) When intended, volumes greater than 20% of the fibroid volume can be successfully ablated (technical effectiveness) The investigators' 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.

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) 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 Evaluating any minor complications or adverse events that result from the MR-guided HIFU treatment 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: 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. 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. 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. Quality of Life questionnaires: the SF-36(http://www.sf36.org/tools/SF36.shtml) and UFS-QoL (which includes SSS)

Pre- or peri-menopausal women with symptomatic uterine fibroids who desire a uterine sparing procedure receive a treatment with the Philips MRI-guided HIFU system. Patients must have completed child bearing prior to enrolling in this study.

HIFU is the use of focused ultrasound energy to penetrate 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 number of Adverse Events reported during the study, divided by the total number of treated subjects. This corresponds to the mean number of Adverse Events per subject.

Fibroid Symptom Severity Score (SSS) From the Uterine Fibroid Symptoms - Quality of Life (UFS-QoL) Questionnaire.

Mean absolute change in the Symptom Severity Score (SSS) of the Uterine Fibroid Symptoms - Quality of Life (UFS-QoL) questionnaire after fibroid treatment with HIFU. The SSS is a scale from 0-100, where 0 corresponds to no symptoms and 100 corresponds to the most severe symptoms.

Inclusion Criteria: Women, age between 18 and 59 years Weight < 140kg Pre- or peri-menopausal Uterine size < 24 weeks Transformed SSS score > 40 Normal Cervical cell assessment by PAP Symptomatic Fibroid disease Dominant fibroid greater than or equal to 3cm and less than or equal to 12 cm Exclusion Criteria: Other Pelvic Disease Desire for future pregnancy Significant systemic disease even if controlled Positive pregnancy test Hematocrit < 25% Scarring or other interference of the HIFU beam MRI or contrast contraindicated Fibroids not quantifiable on MRI Calcifications around or throughout uterine tissues Communication barrier

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