NCT06726330

Risk-reducing Strategies, Including Fimbriectomy, in Women With a Germline Mutation Predisposing to Ovarian or Pelvic Cancer

Evaluation of Risk Control of Advanced Stage Tubo-ovarian or Primary Peritoneal Carcinoma Associated With Ovarian Carcinoma Risk-reducing Strategies, Including Fimbriectomy With Delayed Oophorectomy, in Women With a Germline Mutation Predisposing to Ovarian or Pelvic Cancer

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 1,100 (estimated)
• Sponsor: Centre Oscar Lambret · Academic / Other
• Sex: Female
• Age: 35 Years – 50 Years
• Healthy volunteers: Not accepted

Summary

• FIMBRIMENOP-2402 study aims to evaluate the long-term management of cancer risks in premenopausal women who have a genetic predisposition to tubo-ovarian or primary peritoneal carcinoma, such as mutations in BRCA1, BRCA2, RAD51C, RAD51D, or PALB2 genes. This study offers an alternative to standard preventive surgery (bilateral salpingo-oophorectomy or BSO) by exploring the use of fimbriectomy (removal of the fallopian tube's fimbria) followed by delayed oophorectomy (removal of ovaries at menopause). It's a pragmatic multicenter trial conducted across various medical centers, employing a non-randomized controlled preference design to compare two preventive surgical strategies: 1. Fimbriectomy followed by delayed oophorectomy (F-DO). 2. Bilateral salpingo-oophorectomy (BSO). The primary objective is to compare the long-term efficacy of two preventive surgical strategies : 1. Fimbriectomy followed by delayed oophorectomy (F-DO). 2. Bilateral salpingo-oophorectomy (BSO). As for the design of the study, participants choose their preferred surgical strategy during or after oncogenetic counseling, ensuring patient autonomy in decision-making. • Follow-Up: Long-term follow-up includes clinical assessments, data collection from medical networks, and integration with national health databases to track outcomes up to the age of 70. This is the first French comparative study in real-world settings and is classified as interventional research (RIPH1) under French regulations, given the need to validate fimbriectomy efficacy.

Detailed description

* The FIMBRIMENOP-2402 study is a pragmatic, multicenter, interventional trial (RIPH1) designed to evaluate long-term management strategies for reducing cancer risk in premenopausal women genetically predisposed to tubo-ovarian or primary peritoneal carcinoma. Women carrying mutations in BRCA1, BRCA2, RAD51C, RAD51D, or PALB2 genes are the primary focus of this investigation. * Objectives The primary objective is to evaluate, on a long-term horizon, the control of the risk of advanced stage tubo-ovarian or primary peritoneal carcinoma according to the chosen care pathway, and more specifically whether F-DO is non inferior to BSO, in women with a germline mutation predisposing to the risk of high grade serous tubo-ovarian or primary peritoneal carcinoma. The study aims to determine whether F-DO is non-inferior to BSO in controlling the risk of advanced-stage tubo-ovarian or primary peritoneal carcinoma in high-risk women. The secondary objectives include evaluating the benefit-risk ratio of these approaches by assessing: * Menopause-related side effects, such as cardiovascular and osteoporosis-related events. * Surgical complications and overall survival. * Long-term oncological outcomes, including breast cancer risks. * Patient-reported preferences and compliance with the chosen pathway. The study will also contribute to a prospective meta-analysis of similar international studies. • Design and Methodology The study employs a non-randomized controlled preference design, allowing participants to choose their preventive surgical strategy after informed counseling with oncogeneticists and gynecologic surgeons. This approach promotes patient autonomy while reflecting real-world clinical decision-making. Participants may revise their choice at any time before the first surgical intervention. The actual treatment received or the final preference will define the "care pathway". • Population and Recruitment The study will enroll 1,100 premenopausal women aged 35-50 years from multiple French centers, all of whom are at an elevated genetic risk for tubo-ovarian or primary peritoneal carcinoma. Recruitment is expected to span five years, with follow-up continuing until participants reach 70 years of age. • Data Collection and Follow-Up Data collection integrates multiple sources to ensure comprehensive coverage of outcomes: 1. Annual Clinical Assessments: Participants undergo routine clinical evaluations, including physician visits, medical reports, and online questionnaires or phone interviews. 2. Regional Oncogenetic Networks: Data from regional networks are incorporated to monitor oncological events and compliance. 3. French Administrative Health Database (SNDS): Extraction of anonymized health records ensures the completeness of reported events and reduces logistical complexity. * Endpoints : * Primary Endpoint : The incidence of advanced-stage (stage III or IV) tubo-ovarian or primary peritoneal carcinoma, measured as the time from study entry to the occurrence of cancer, with death without cancer as a competing event. Censoring will occur at the last follow-up visit for women without cancer. * Secondary Endpoints include : * Incidence of tubo-ovarian carcinoma at any stage, breast cancer, cardiovascular and osteoporosis-related events. * Age at menopause. * Surgical complications within 30 days post-surgery, graded per NCI-CTCAE V5.0. * Statistical Analysis The final analysis will occur when all participants have been followed for 35 years, with interim analyses planned every six years or upon reporting of 10 events. Data will be analyzed to compare oncological outcomes, quality of life, and survival between the F-DO and BSO groups. Biases inherent in the preference design will be addressed through appropriate statistical modeling. • Ethical Considerations The study adheres to French regulatory requirements, including patient data confidentiality under the GDPR and ethical review by relevant committees. Informed consent will be obtained from all participants, with clear communication of risks and benefits. By evaluating the efficacy and safety of F-DO, this study has the potential to redefine preventive surgical strategies, optimizing outcomes for women at high genetic risk of ovarian cancer.

Conditions

• Tubo-ovarian Carcinoma
• High-grade Serous Carcinoma
• Primary Peritoneal Carcinoma Stage III
• Primary Peritoneal Carcinoma Stage IV
• Primary Peritoneal Carcinoma

Interventions

Type	Name	Description
PROCEDURE	Fimbriectomy Followed by Delayed Oophorectomy (F-DO)	This intervention involves two stages: 1. Fimbriectomy: A preventive surgical procedure that removes the fimbrial end of the fallopian tubes, including adjacent ovarian tissue, while preserving ovarian function to avoid premature menopause. 2. Delayed Oophorectomy: The removal of ovaries, performed at menopause or later, depending on patient preference and clinical guidelines. * The F-DO strategy aims to reduce the risk of tubo-ovarian or primary peritoneal carcinoma, which often originates in the fallopian tubes, while minimizing the adverse effects of premature menopause such as cardiovascular disease and osteoporosis
PROCEDURE	Bilateral Salpingo-Oophorectomy	This standard surgical intervention involves the removal of both fallopian tubes and ovaries (BSO) to eliminate the risk of tubo-ovarian or primary peritoneal carcinoma. It is typically recommended for women with a genetic predisposition (e.g., BRCA1/2 mutations) around the age of 40-45. While highly effective in preventing cancer, BSO induces premature menopause, which may result in long-term side effects such as increased cardiovascular risk, osteoporosis, and cognitive decline.

Timeline

• Start date: 2027-03-01
• Primary completion: 2071-03-01
• Completion: 2071-03-01
• First posted: 2024-12-10
• Last updated: 2026-03-17

Locations

23 sites across 1 country: France