Sonalleve Fibroid Ablation Pivotal Clinical Trial for MR-HIFU of Uterine Fibroids (SOFIA)

• Alternative Interventional Treatment (AIT) [ Time Frame: 12 months after HIFU treatment ] [ Designated as safety issue: No ]

  AIT is scored dichotomously as follows:

  0 = Failure. Failure occurs if an AIT for fibroid related symptoms is administered within 12 months of study treatment.

  1 = Success. Success occurs if no AIT is administered for fibroid related symptoms within 12 months of study treatment.

  An AIT is defined as being one of the following: hysterectomy, myomectomy, uterine artery embolization, endometrial ablation and resection, or another MR-HIFU treatment (with the exception of a 're-treatment' as defined in the protocol, e.g. because of temporarily inaccessible fibroids).

• Menstrual Blood Loss (MBL) [ Time Frame: at baseline and at 12 months following treatment ] [ Designated as safety issue: No ]

  Menstrual Blood Loss (MBL) scored dichotomously as follows:

  0 = Failure. Failure occurs if the change from baseline in MBL measurement is < 50 % as measured with alkaline hematin test (AHT) method.

  1 = Success. Success occurs if the change from baseline in MBL measurement is >= 50 %, or if the MBL is < 80 ml as measured with the AHT method.

• Return to Activity [ Time Frame: 72 hours ] [ Designated as safety issue: No ]

  Length for Return to Activity after HIFU treatment measured dichotomously:

  0 = Failure. If subject takes longer than 72 hours to return to work or normal activity.

  1 = Success. If subject returns to work or normal activity within 72 hours inclusive.

• Symptom Severity Score (SSS) [ Time Frame: at baseline and at 12 months following treatment ] [ Designated as safety issue: No ]

  Symptom Severity Score (SSS) of Uterine Fibroid Symptom and Quality of Life questionnaire (UFS-QoL), assessed dichotomously at 12 months:

  0 = Failure. Reduction of less than 10 points on SSS.

  1 = Success. Reduction of at least 10 points on SSS.

The purpose of this clinical study is to determine whether treatment with the Philips Sonalleve Magnetic Resonance-guided High Intensity Focused Ultrasound (MR-HIFU) system is effective in the treatment symptomatic uterine leiomyomas (uterine fibroids).

Uterine Fibroids are the most common benign tumors in pre- and peri-menopausal women. Fibroids occur in 20-50% of women over 30 years of age, and with increasing size can produce pain, menorrhagia, pressure, bloating and urinary and bowel compression symptoms. Fibroids may also cause infertility. 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, or treatments causing necrosis of the fibroid tissue such as ablation (freezing or heating) or embolization. It has been estimated that 600,000 hysterectomies are performed per year in the United States and more than half of the conducted hysterectomies are due to fibroids. 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. However, High Intensity Focused Ultrasound (HIFU) shows promising results in relieving fibroid symptoms.

This study will confirm the safety and clinical effectiveness of Philips Sonalleve MR-HIFU Fibroid Therapy system for ablating symptomatic fibroids.

• Device: MR-HIFU treatment
  A treatment session with the Philips Sonalleve MR-HIFU device for thermal ablation of uterine fibroids with high-intensity focused ultrasound.
  Other Name: Philips Sonalleve MR-HIFU Uterine Fibroid Therapy
• Device: Sham treatment
  A pretend treatment session with the Philips Sonalleve MR-HIFU system in which no therapeutic ultrasound doses are delivered.
  Other Name: pretend treatment with Philips Sonalleve MR-HIFU

• Experimental: MR-HIFU treatment
  Patients receiving MR-HIFU treatment
  Intervention: Device: MR-HIFU treatment
• Sham Comparator: Sham Treatment
  Patients receiving sham treatment
  Intervention: Device: Sham treatment

• Voogt MJ, Trillaud H, Kim YS, Mali WP, Barkhausen J, Bartels LW, Deckers R, Frulio N, Rhim H, Lim HK, Eckey T, Nieminen HJ, Mougenot C, Keserci B, Soini J, Vaara T, Köhler MO, Sokka S, van den Bosch MA. Volumetric feedback ablation of uterine fibroids using magnetic resonance-guided high intensity focused ultrasound therapy. Eur Radiol. 2012 Feb;22(2):411-7. Epub 2011 Sep 8.
• Spies JB, Coyne K, Guaou Guaou N, Boyle D, Skyrnarz-Murphy K, Gonzalves SM. The UFS-QOL, a new disease-specific symptom and health-related quality of life questionnaire for leiomyomata. Obstet Gynecol. 2002 Feb;99(2):290-300.
• Stewart EA, Gedroyc WM, Tempany CM, Quade BJ, Inbar Y, Ehrenstein T, Shushan A, Hindley JT, Goldin RD, David M, Sklair M, Rabinovici J. Focused ultrasound treatment of uterine fibroid tumors: safety and feasibility of a noninvasive thermoablative technique. Am J Obstet Gynecol. 2003 Jul;189(1):48-54.
• Hindley J, Gedroyc WM, Regan L, Stewart E, Tempany C, Hynyen K, Mcdannold N, Inbar Y, Itzchak Y, Rabinovici J, Kim HS, Geschwind JF, Hesley G, Gostout B, Ehrenstein T, Hengst S, Sklair-Levy M, Shushan A, Jolesz F. MRI guidance of focused ultrasound therapy of uterine fibroids: early results. AJR Am J Roentgenol. 2004 Dec;183(6):1713-9. Erratum in: AJR Am J Roentgenol. 2005 Jan;184(1):348. Hynnen, Kullvro [corrected to Hynyen, Kullervo]; Macdanold, Nathan [corrected to Mcdannold, Nathan]; Kim, Kevin [corrected to Kim, Hyun S]; Gostout, Brian [corrected to Gostout, Bobbie].
• Leon-Villapalos J, Kaniorou-Larai M, Dziewulski P. Full thickness abdominal burn following magnetic resonance guided focused ultrasound therapy. Burns. 2005 Dec;31(8):1054-5. Epub 2005 Jun 20. No abstract available.
• Fennessy FM, Tempany CM. MRI-guided focused ultrasound surgery of uterine leiomyomas. Acad Radiol. 2005 Sep;12(9):1158-66. Review.
• Stewart EA, Rabinovici J, Tempany CM, Inbar Y, Regan L, Gostout B, Hesley G, Kim HS, Hengst S, Gedroyc WM. Clinical outcomes of focused ultrasound surgery for the treatment of uterine fibroids. Fertil Steril. 2006 Jan;85(1):22-9. Erratum in: Fertil Steril. 2006 Apr;85(4):1072. Gastout, Bobbie [corrected to Gostout, Bobbie]; Gedroye, Wladyslaw M [corrected to Gedroyc, Wladyslaw M].
• Fennessy FM, Tempany CM, McDannold NJ, So MJ, Hesley G, Gostout B, Kim HS, Holland GA, Sarti DA, Hynynen K, Jolesz FA, Stewart EA. Uterine leiomyomas: MR imaging-guided focused ultrasound surgery--results of different treatment protocols. Radiology. 2007 Jun;243(3):885-93. Epub 2007 Apr 19.
• Mara M, Fucikova Z, Maskova J, Kuzel D, Haakova L. Uterine fibroid embolization versus myomectomy in women wishing to preserve fertility: preliminary results of a randomized controlled trial. Eur J Obstet Gynecol Reprod Biol. 2006 Jun 1;126(2):226-33. Epub 2005 Nov 15.
• Stewart EA, Gostout B, Rabinovici J, Kim HS, Regan L, Tempany CM. Sustained relief of leiomyoma symptoms by using focused ultrasound surgery. Obstet Gynecol. 2007 Aug;110(2 Pt 1):279-87.
• Taran FA, Tempany CM, Regan L, Inbar Y, Revel A, Stewart EA; MRgFUS Group. Magnetic resonance-guided focused ultrasound (MRgFUS) compared with abdominal hysterectomy for treatment of uterine leiomyomas. Ultrasound Obstet Gynecol. 2009 Nov;34(5):572-8.
• Funaki K, Fukunishi H, Sawada K. Clinical outcomes of magnetic resonance-guided focused ultrasound surgery for uterine myomas: 24-month follow-up. Ultrasound Obstet Gynecol. 2009 Nov;34(5):584-9.
• Okada A, Morita Y, Fukunishi H, Takeichi K, Murakami T. Non-invasive magnetic resonance-guided focused ultrasound treatment of uterine fibroids in a large Japanese population: impact of the learning curve on patient outcome. Ultrasound Obstet Gynecol. 2009 Nov;34(5):579-83.
• Kim YS, Lim HK, Kim JH, Rhim H, Park BK, Keserci B, Köhler MO, Bae DS, Kim BG, Lee JW, Kim TJ, Sokka S, Lee JH. Dynamic contrast-enhanced magnetic resonance imaging predicts immediate therapeutic response of magnetic resonance-guided high-intensity focused ultrasound ablation of symptomatic uterine fibroids. Invest Radiol. 2011 Oct;46(10):639-47.

Inclusion Criteria:

• Women, age between 18 and 50 years
• Ethnicity has a match with the intended profile for the site
• Weight < 140kg or 310lbs
• Pre- or peri-menopausal as indicated by clinical evaluation or Follicle Stimulating Hormone (FSH) level < 40 IU/L
• Willing and able to attend all study visits
• Willing and able to complete Menstrual Blood Loss (MBL) assessment with Alkaline Hematin (AH) method
• Willing and able to use reliable contraception methods
• Uterine size < 24 weeks
• Cervical cell assessment by Pap smear: Normal, Low Grade Squamous Intraepithelial Lesion (SIL), Low risk Human Papillomavirus (HPV) or Atypical Squamous Cells of Uncertain Significance (ASCUS) subtypes of cervical tissue
• MR-HIFU device accessibility to fibroids such that at least 50% of the total fibroid volume can be treated.

• Fibroids selected for treatment meeting the following criteria (further extrapolated in the protocol):

  1. Total planned ablation volume of all fibroids should not exceed 250 ml and
  2. No more than 5 fibroids should be planned for ablation and
  3. Dominant fibroid (diameter) is greater than or equal to 3 cm and
  4. Completely non-enhancing fibroids should not be treated as the identification of treated volume becomes ambiguous
• Patient's self-assessment indicates that she has had episodes of heavy menstrual bleeding in the past 6 months.
• Menstrual Blood Loss (MBL) ≥150 ml and ≤ 500 ml

Exclusion Criteria:

• Other Pelvic Disease (Other mass, endometriosis, ovarian tumor, acute pelvic disease, significant adenomyosis)
• Desire for future pregnancy
• Significant systemic disease even if controlled
• Positive pregnancy test
• Hematocrit < 25%
• Extensive scarring along anterior lower abdominal wall (>50% of area)
• Surgical clips in the potential path of the HIFU beam
• MRI contraindicated
• MRI contrast agent contraindicated (including renal insufficiency)
• Calcifications around or throughout uterine tissues that may affect treatment
• Communication barrier
• Highly perfused or brighter than myometrium in T2-weighted MRI (according to the T2 contrast obtained using the Philips MR-HIFU MR protocol) fibroids
• Fibroids not quantifiable on MRI (e.g. multi-fibroid cases where volume measurements are not feasible)
• Menses lasting > 7 days or intermenstrual bleeding (patient can be included if there is endometrial biopsy within 6 months to exclude malignancy)

• Patient is currently on hormonal medication for fibroids or has a hormonal medication history as described below:

  1. 1-month Lupron dose or equivalent: less than 1 month prior to MBL measurement or
  2. 3-month Lupron dose or equivalent: less than 3 months prior to MBL measurement or
  3. Depo Provera or equivalent: less than 6 months prior to MBL measurement