TUBectomy With Delayed Oophorectomy in High Risk Women to Assess the Safety of Prevention

Официальное название

TUBectomy With Delayed Oophorectomy as Alternative for Risk-reducing Salpingo-oophorectomy in High Risk Women to Assess the Safety of Prevention: TUBA-WISP II Study.

Обзор

The aim of the project is to evaluate the risk-reducing salpingectomy with delayed oophorectomy as an alternative for risk-reducing salpingo-oophorectomy in high risk women with respect to ovarian cancer incidence.

Подробное описание

In BRCA1/2 gene mutation carriers, a risk-reducing salpingo-oophorectomy (RRSO) is recommended around the age of 40. This recommendation is based on a 10-40% life-time risk of ovarian cancer in this population and disappointing results of ovarian cancer surveillance for early detection. Moreover, the mortality rate of ovarian cancer is high. Effects of RRSO are a decrease in ovarian cancer risk (80-96%) on one hand and immediate onset of menopause and non-cancer related morbidity on the other hand. The fifty percent breast cancer risk reduction after RRSO has become disputable in the last years. Based on multiple studies showing that most high-grade serous ovarian cancers develop at the distal end of the Fallopian tube, an innovative strategy for RRSO has been developed for this study proposal: risk-reducing salpingectomy (RRS) with delayed risk-reducing oophorectomy (RRO). However, the safety of this strategy has not been proven yet. Before implementing this innovative strategy as standard care we need to investigate the long term effects on ovarian cancer incidence.

Вмешательства

• Процедура Risk-reducing salpingectomy with delayed oophorectomy
  * BRCA1: RRS at age 25-40 and RRO at a maximum age of 45 (advised between 35 and 45). * BRCA2: RRS at age 25-45 and RRO at a maximum age of 50 (advised between age 40 and 50). * BRIP1, RAD51C, RAD51D: RRS at age 25-50 and RRO at a maximum age of 55 (advised between 45 and 55)
• Процедура Risk-reducing salpingo-oophorectomy
  * BRCA1 at a maximum age of 40 (advised between age 35 and 40) * BRCA2 at a maximum age of 45 (advised between age 40 and 45) * BRIP1, RAD51C, RAD51D: at a maximum age of 50 (advised between 45 and 50)

Первичные конечные точки

• High grade serous (ovarian) cancer incidence [Срок оценки: Until the age of 45 for BRCA1 and 50 for BRCA2 germline mutation carriers]

Вторичные конечные точки (5)

• Incidence of (pre)malignant findings in tubes/ovaries [Срок оценки: 6 weeks after each surgery]
• Peri-operative morbidity and mortality [Срок оценки: 6 weeks after each surgery]
• Incidence of pelvic cancer (other than ovarian cancer) [Срок оценки: Up to the age of 70]
• Incidence of breast cancer [Срок оценки: Up to the age of 70]
• Uptake of risk reducing oophorectomy [Срок оценки: Up to the age of 70]

Критерии участия

Критерии включения

• Women with a class 5 (definitely pathogenic) BRCA1, BRCA2, RAD51C, RAD51D or BRIP1 germline mutation in one of the participating centers.
• Age at inclusion;

• BRCA1: 25-40 years
• BRCA2: 25-45 years
• RAD51C, RAD51D, BRIP1: 25-50 years
• Childbearing completed
• Presence of at least one fallopian tube
• Participants may have a personal history of non-ovarian malignancy
• Informed consent must be obtained and documented according to national and local regulatory requirements and the local rules followed in the institution.

Критерии исключения

• Postmenopausal status (natural menopause or due to treatment)
• Wish for second stage RRO within two years after RRS
• Legally incapable
• Prior bilateral salpingectomy
• A personal history of ovarian, fallopian tube or peritoneal cancer
• Current diagnosis or treatment for malignant disease

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

Австралия · 15 центров

• Chris O'Brien Lifehouse — Sydney
• Westmead hospital — Sydney
• St Andrew War Memorial Hospital — Brisbane
• Royal Brisbane Hospital — Brisbane
• Greenslopes Private Hospital — Brisbane
• Royal Adelaide Hospital — Adelaide
• Frances Perry House — Melbourne
• Mercy Hospital — Melbourne
• … и ещё 7 центров

Нидерланды · 15 центров

• Radboudumc — Nijmegen
• Maastricht University Medical Center — Maastricht
• Catharina Ziekenhuis — Eindhoven
• Elisabeth-TweeSteden Ziekenhuis — Tilburg
• Amsterdam University Medical Center — Amsterdam
• Antoni van Leeuwenhoek — Amsterdam
• Amphia — Breda
• Medisch Spectrum Twente — Enschede
• … и ещё 7 центров

США · 11 центров

• UChicago Medicine — Chicago
• Dana Farber Cancer Institute — Boston
• Mayo Clinic — Rochester
• Washington University Medical Center — St Louis
• Mount Sinai Hospital — New York
• Memorial Sloan Kettering Cancer Center — New York
• Duke University Hospital — Durham
• Hospital of the University of Pennsylvania — Philadelphia
• … и ещё 3 центра

Германия · 4 центра

• Klinikum St. Marien Amberg — Amberg
• Evangelische Waldkrankenhaus Spandau Berlin — Berlin-Spandau
• Klinikum Lippe Detmold — Detmold
• Evang. Kliniken Essen-Mitte — Essen

Италия · 4 центра

• Universita di Bologna — Bologna
• Humanitas San Pio X — Milan
• San Gerardo Hospital — Monza
• Gemelli Hospital — Rome

Польша · 4 центра

• Gdynia Oncology Centre — Gdynia
• Bonifraterskie Centrum Medyczne — Katowice
• Medical University of Silesia — Katowice
• National Cancer Institute Warsaw — Warsaw

Норвегия · 3 центра

• Akershus University Hospital — Nordbyhagen
• Oslo University Hospital — Oslo
• Stavanger Uniersity Hospital — Stavanger

Бельгия · 2 центра

• Hopital Universitaire Bruxelles — Brussels
• Universitair Ziekenhuis Leuven — Leuven

Австрия · 1 центр

• Medical University of Graz — Graz

Бразилия · 1 центр

• AC Camargo Cancer Centre — São Paulo

Канада · 1 центр

• Vancouver General Hospital — Vancouver

Ирландия · 1 центр

• Cork University Hospital — Cork

Мексика · 1 центр

• Instituto Nacional de Cancerología — Mexico City

Испания · 1 центр

• Vall D'Hebron Barcelona — Barcelona

Швеция · 1 центр

• Karolinksa Institutet — Stockholm

Uruguay · 1 центр

• Hospital Británico — Montevideo

Публикации

• Pennington KP, Pugh SL, Huh W, Walker JL, Jewell E, Havrilesky LJ, Carter J, Muller CY, Drapkin R, Lankes HA, Castellano T, Zamorano AS, Blank SV, Kachnic LA. Optimization of Timing for Risk-Reducing Salpingectomy and Oophorectomy. Obstet Gynecol. 2025 Jan 1;145(1):21-30. doi: 10.1097/AOG.0000000000005781. Epub 2024 Nov 7. PMID 39509704
• Steenbeek MP, van Bommel MHD, intHout J, Peterson CB, Simons M, Roes KCB, Kets M, Norquist BM, Swisher EM, Hermens RPMG; TUBA-WISP II consortium; Lu KH, de Hullu JA. TUBectomy with delayed oophorectomy as an alternative to risk-reducing salpingo-oophorectomy in high-risk women to assess the safety of prevention: the TUBA-WISP II study protocol. Int J Gynecol Cancer. 2023 Jun 5;33(6):982-987. doi: PMID 37045546

Идентификаторы

NCT: NCT04294927 · NL 70691.091.19

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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