Clinical trial NCT06726330: Risk-reducing Strategies, Including Fimbriectomy, in Women With a Germline Mutation Predisposing to Ovarian or Pelvic Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Tubo-ovarian Carcinoma
High-grade Serous Carcinoma
Primary Peritoneal Carcinoma Stage III
Primary Peritoneal Carcinoma Stage IV
Primary Peritoneal Carcinoma
Keywords: Tubo-ovarian carcinoma
Primary peritoneal carcinoma
BRCA1/2 mutations
RAD51C/D mutations
PALB2 mutation
Preventive surgery
Fimbriectomy
Bilateral salpingo-oophorectomy
BSO
Cancer prevention
Premenopausal women
Genetic predisposition to cancer
Lead sponsor: Centre Oscar Lambret
Sponsor class: OTHER
First posted: 2024-12-10
Enrollment: 1100
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a non-randomized controlled preference trial. Participants decide their surgical approach based on counseling. The study accommodates real-world clinical practices, empowering patients in the decision-making process.
Primary purpose: PREVENTION

Brief 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.

Eligibility criteria: Inclusion Criteria:

1. Woman between 35 to 50 years
2. Addressed to or followed in an oncogenetic counselling
3. Identified risk of tubo-ovarian or primary peritoneal carcinoma based on mutational status (BRCA1, BRCA 2, RAD51C, RAD51D, PALB2). The list of considered mutations may be extended during the study.
4. Written informed consent
5. Patient covered by the French "Social Security"

Exclusion Criteria:

1. Prior bilateral oophorectomy and/or bilateral salpingectomy for any reason (prophylactic surgery or other)
2. Personal history of ovarian, fallopian tube or primary peritoneal cancer
3. Menopause defined by

   • In women without prior chemotherapy If no prior hysterectomy: the absence of menses for at least 12 months, or FSH \> 20 UI/L with low estrogen level with no identified gynecological or endocrine explanation. Amenorrhea related to an intrauterine device, vaginal ring or estrogen-progestin pill will not be considered as menopause.

   If prior hysterectomy: FSH \>20 UI/L with low estrogen level (with or without vasomotor symptoms, genitourinary symptoms)
   * In women with prior chemotherapy: the absence of menses for at least 24 months
   * In all women with progesterone-loaded intra-uterine device (IUD): FSH \> 20 UI/L with low estrogen level
4. Inability to comply with medical follow-up of the trial (geographical, social or psychological reasons)
5. Patient under guardianship or curatorship

Primary outcomes:
measure: Incidence of Advanced-Stage (Stage III or IV) Tubo-Ovarian or Primary Peritoneal Carcinoma
timeFrame: Up to 70 years of age
Secondary outcomes:
measure: Incidence of Any-Stage Tubo-Ovarian or Primary Peritoneal Carcinoma
timeFrame: Up to 70 years of age
measure: Age at Menopause
timeFrame: Over the study period (up to age 70).
measure: Incidence of Cardiovascular Events and Osteoporosis-Related Events
timeFrame: Over the study period (up to age 70)
measure: Overall Survival
timeFrame: From study entry to death from any cause.
measure: Surgical Complications
timeFrame: 30 days following the surgery
Other outcomes:
measure: Benefit-Risk Ratio Analysis
timeFrame: Over the study period (up to age 70)
Locations:
city: Bordeaux
country: France
facility: Institut Bergonié
city: Caen
country: France
facility: Centre François Baclesse
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Dijon
country: France
facility: Centre Hospitalier Universitaire Dijon Bourgogne
city: Grenoble
country: France
facility: Centre hospitalier universitaire Grenoble-Alpes
city: Lille
country: France
facility: Centre Hospitalier Universitaire de Lille
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lille
country: France
facility: Clinique du Bois
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Nantes
country: France
facility: Institut de cancérologie de l'Ouest Centre René GAUDUCHEAU
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Gustave Roussy
city: Paris
country: France
facility: Hôpital de la Pitié Salpêtrière - AP-HP
city: Paris
country: France
facility: Hôpital Institut CURIE
city: Paris
country: France
facility: Hôpital Tenon AP-HP
city: Reims
country: France
facility: Institut Godinot
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Rouen
country: France
facility: Hôpitaux Privés Rouennais
city: Saint-Cloud
country: France
facility: Hôpital de Saint-Cloud
city: Toulouse
country: France
facility: Institut universitaire du cancer de Toulouse
city: Troyes
country: France
facility: Hôpital Simone Veil - CH de Troyes
city: Valenciennes
country: France
facility: Centre Hospitalier de Valenciennes
Study officials:
affiliation: Centre Oscar Lambret
name: Carlos MARTINEZ GOMEZ, MD
role: STUDY_DIRECTOR
affiliation: Centre Oscar Lambret
name: Audrey MAILLIEZ, MD
role: STUDY_DIRECTOR
References: