Risk Reducing Salpingectomy With Delayed Oophorectomy as an Alternative to Risk- Reducing Salpingo-oophorectomy in High Risk-Women to Assess the Safety of Prevention - US Cohort Study

Study Overview
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Brief Summary
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This is a prospective preference study that will evaluate non-inferiority of the innovative treatment (RRS with delayed RRO) as compared to the standard treatment (RRSO) with respect to high grade serous (ovarian) cancer incidence

Detailed Description
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The aim of the project is to evaluate RRS with delayed RRO as an alternative for RRSO in BRCA1/2 gene germline mutation carriers with respect to ovarian cancer incidence. We hypothesize that postponement of oophorectomy and consequent menopause to the age of 40-45 (BRCA1) or 45-50 (BRCA2) compared to current standard RRSO at age 35-40 (BRCA1) or 40-45 (BRCA2) will not lead to a significant increase in ovarian cancer risk. PRIMARY OBJECTIVE: To evaluate non-inferiority of the innovative treatment (RRS with delayed RRO) as compared to the standard treatment (RRSO) with respect to high grade serous (ovarian) cancer incidence in BRCA1/2 gene germline mutation carriers. SECONDARY OBJECTIVE: Incidence of (pre)malignant findings in tubes/ovaries, perioperative morbidity and mortality, incidence of non-ovarian pelvic cancer, breast cancer, prophylactic breast surgery and uptake of risk reducing oophorectomy. EXPLORATORY OBJECTIVE: Estimate high grade serous (ovarian) cancer incidence for innovative and standard treatments in BRIP1, RAD51C, and RAD51D gene germline mutation carriers

Official Title
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Risk Reducing Salpingectomy With Delayed Oophorectomy as an Alternative to Risk- Reducing Salpingo-oophorectomy in High Risk-Women to Assess the Safety of Prevention - US Cohort Study

Conditions
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Fallopian Tube Cancer, Ovarian Cancer

Intervention / Treatment
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* Other: RIsk-Reducing Salpingectomy (RRS)
* Other: Risk-Reducing Oophorectomy-RRO
* Other: Risk-Reducing Salpingo-Oophorectomy-RRSO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Premenopausal women with a documented deleterious mutation in BRCA1, BRCA2, BRIP1, RAD51C and/or RAD51D gene germline mutation. Age 25-40 years for BRCA1 mutation carriers, 25-45 years for BRCA2 and 30-50 years for BRIP1, RAD51C, RAD51D Childbearing completed or no longer requires fallopian tubes Presence of at least one fallopian tube Participants may have a personal history of non-ovarian malignancy. Informed consent must be obtained and documented. Exclusion Criteria: Postmenopausal status (natural menopause or due to (cancer) treatment) Wish for second stage RRO within two years after RRS (if clear at enrollment) Legally incapable Prior bilateral salpingectomy A personal history of ovarian, fallopian tube or peritoneal cancer Current clinicals signs, diagnosis or treatment for malignant disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Risk-Reducing Salpingectomy-RRS<br>Can help to lower the risk of ovarian cancer with a delayed removal of 1. | Other: RIsk-Reducing Salpingectomy (RRS)<br>* complete questionnaires, standard-of-care laparoscopy to check the abdominal area before the assigned procedure<br>|
| Other: Risk-Reducing Oophorectomy-RRO<br>Can help to lower the risk of ovarian cancer removing both fallopian tubes. | Other: Risk-Reducing Oophorectomy-RRO<br>* complete questionnaires, standard-of-care laparoscopy to check the abdominal area before the assigned procedure<br>|
| Other: Risk-Reducing Salpingo-Oophorectomy-RRSO<br>Can help to lower the risk of ovarian cancer as well as the standard-of-care risk-reducing procedure involving the removal of the fallopian tubes and ovaries (risk-reducing salpingo-oophorectomy-RRSO) | Other: Risk-Reducing Salpingo-Oophorectomy-RRSO<br>* complete questionnaires, standard-of-care laparoscopy to check the abdominal area before the assigned procedure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the non-inferiority of the innovative treatment (RRS with delayed RRO) as compared to the standard treatment (RRSO) with respect to high grade serous (ovarian) cancer incidence in BRCA1/2 gene germline mutation carriers. |  | through study completion, an average of 1 year |