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

Not Applicable
Recruiting
Conditions
BRIP1 Gene Mutation
BRCA1 Gene Mutation
RAD51D Gene Mutation
BRCA2 Gene Mutation
Ovarian Cancer
RAD51C Gene Mutation
Interventions
Procedure: Risk-reducing salpingo-oophorectomy
Procedure: Risk-reducing salpingectomy with delayed oophorectomy
Registration Number
NCT04294927
Lead Sponsor
University Medical Center Nijmegen
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
Female
Target Recruitment
3000
Inclusion Criteria
  • 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.

Exclusion Criteria
  • 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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Risk-reducing salpingo-oophorectomyRisk-reducing salpingo-oophorectomyRisk-reducing salpingo-oophorectomy.
Risk-reducing salpingectomy with delayed oophorectomyRisk-reducing salpingectomy with delayed oophorectomyRisk-reducing salpingectomy after the completion of childbearing with delayed oophorectomy.
Primary Outcome Measures
NameTimeMethod
High grade serous (ovarian) cancer incidenceUntil the age of 45 for BRCA1 and 50 for BRCA2 germline mutation carriers

High grade serous (ovarian) cancer incidence

Secondary Outcome Measures
NameTimeMethod
Incidence of (pre)malignant findings in tubes/ovaries6 weeks after each surgery

Incidence of (pre)malignant findings in tubes/ovaries at risk-reducing salpingectomy, oophorectomy and salpingo-oophorectomy.

Incidence of pelvic cancer (other than ovarian cancer)Up to the age of 70

Incidence of pelvic cancer (other than ovarian cancer)

Peri-operative morbidity and mortality6 weeks after each surgery

Peri-operative morbidity and mortality

Incidence of breast cancerUp to the age of 70

Incidence of breast cancer

Uptake of risk reducing oophorectomyUp to the age of 70

Uptake of risk reducing oophorectomy after risk reducing salpingectomy

Trial Locations

Locations (37)

Dana Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

MD Anderson Cancer Centre

🇺🇸

Houston, Texas, United States

University of Washington

🇺🇸

Seattle, Washington, United States

Radboudumc

🇳🇱

Nijmegen, Gelderland, Netherlands

Antoni van Leeuwenhoek

🇳🇱

Amsterdam, Netherlands

University Medical Center Groningen

🇳🇱

Groningen, Netherlands

Catharina Ziekenhuis

🇳🇱

Eindhoven, Noord-Brabant, Netherlands

Amsterdam University Medical Center

🇳🇱

Amsterdam, Netherlands

Medisch Spectrum Twente

🇳🇱

Enschede, Netherlands

Isala Klinieken

🇳🇱

Zwolle, Netherlands

Instituto Nacional de Cancerología

🇲🇽

Mexico City, Mexico

Elisabeth-TweeSteden Ziekenhuis

🇳🇱

Tilburg, Brabant, Netherlands

Medical Center Leeuwarden

🇳🇱

Leeuwarden, Netherlands

Maxima Medical Center

🇳🇱

Veldhoven, Netherlands

Stavanger Uniersity Hospital

🇳🇴

Stavanger, Norway

Gdynia Oncology Centre

🇵🇱

Gdynia, Poland

Monash Health

🇦🇺

Melbourne, Australia

Hopital Universitaire Bruxelles

🇧🇪

Brussel, Belgium

Erasmus Medical Center

🇳🇱

Rotterdam, Netherlands

Maastricht University Medical Center

🇳🇱

Maastricht, Limburg, Netherlands

Universitair Ziekenhuis Leuven

🇧🇪

Leuven, Belgium

Akershus University Hospital

🇳🇴

Nordbyhagen, Norway

Medical University of Silesia

🇵🇱

Katowice, Poland

National Cancer Institute Warsaw

🇵🇱

Warsaw, Poland

Hospital Británico

🇺🇾

Montevideo, Uruguay

Leiden University Medical Center

🇳🇱

Leiden, Netherlands

Oslo University Hospital

🇳🇴

Oslo, Norway

Bonifraterskie Centrum Medyczne

🇵🇱

Katowice, Poland

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

Peter MacCallum Centre

🇦🇺

Melbourne, Australia

Universita di Bologna

🇮🇹

Bologna, Italy

Royal Womens Hospital

🇦🇺

Melbourne, Australia

AC Camargo Cancer Centre

🇧🇷

São Paulo, Brazil

San Gerardo Hospital

🇮🇹

Monza, Italy

Gemelli Hospital

🇮🇹

Rome, Italy

Karolinksa Institutet

🇸🇪

Stockholm, Sweden

University Medical Center Utrecht

🇳🇱

Utrecht, Netherlands

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