A Study to Compare Two Surgical Procedures in Individuals With BRCA1 Mutations to Assess Reduced Risk of Ovarian Cancer

Study Overview
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Brief Summary
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This clinical trial studies how well two surgical procedures (bilateral salpingectomy and bilateral salpingo-oophorectomy) work in reducing the risk of ovarian cancer for individuals with BRCA1 mutations. Bilateral salpingectomy involves the surgical removal of fallopian tubes, and bilateral salpingo-oophorectomy involves the surgical removal of both the fallopian tubes and ovaries. This study may help doctors determine if the two surgical procedures are nearly the same for ovarian cancer risk reduction for women with BRCA1 mutations.

Detailed Description
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PRIMARY OBJECTIVE: I. To compare the non-inferiority of bilateral salpingectomy (BLS) with delayed oophorectomy to bilateral salpingo-oophorectomy (BSO) to reduce the risk of ovarian cancer among individuals with deleterious BRCA1 germline mutations. SECONDARY OBJECTIVES: I. To prospectively assess estrogen deprivation symptoms in pre-menopausal BLS patients as measured by the Functional Assessment of Cancer Therapy - Endocrine Symptom (FACT-ES) subscale compared to pre-menopausal patients in the BSO arm. II. To determine if health-related quality of life (QOL) (FACT) is negatively impacted by menopausal symptoms (menopausal symptom checklist-Menopausal Symptom Checklist [MSCL]) and sexual dysfunction (Female Sexual Function Index [FSFI]) in pre-menopausal patients who have undergone BLS, in comparison to normative data (MSCL/FACT-ES) and data from pre-menopausal BSO patients. III. To determine if health-related QOL (FACT) is negatively impacted by cancer distress (Impact of Event Scale [IES]) in individuals who have undergone BLS, in comparison to BSO patients. IV. To assess medical decision making, as measured by the Shared Decision Making Questionnaire (SDM-Q-9) and Decision Regret Scale (DRS), and determine factors associated with the risk of reducing surgical treatment choice. V. To assess adverse events, graded using Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. EXPLORATORY OBJECTIVES: I. Sexual dysfunction, as measured by selected Patient-Reported Outcomes Measurement Information System (PROMIS) screener and external sexual function items (pre-menopausal patients). II. To estimate the cost-effectiveness of BLS compared to BSO for ovarian cancer risk reduction. III. To assess medical decision making, as measured by the Risk-Reducing Medical Decision Making (RR-MDM) survey, a targeted set of questions on risk reducing surgical treatment choice. TRANSLATIONAL RESEARCH OBJECTIVE: I. To bank tissue and blood biospecimens for future research. OUTLINE: Patients are assigned to 1 of 2 groups. GROUP I: Patients undergo bilateral salpingectomy. Patients may then undergo oophorectomy after initial surgery. GROUP II: Patients undergo bilateral salpingo-oophorectomy. Patients in both groups also undergo a transvaginal ultrasound during screening and blood sample collection throughout the trial. After completion of study, patients are followed up at 10-60 days, 6, 12, and 24 months, and then annually for up to 20 years.

Official Title
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A Non-Randomized Prospective Clinical Trial Comparing the Non-Inferiority of Salpingectomy to Salpingo-Oophorectomy to Reduce the Risk of Ovarian Cancer Among BRCA1 Carriers [SOROCk]

Conditions
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Ovarian Carcinoma

Intervention / Treatment
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* Procedure: Bilateral Salpingectomy
* Procedure: Bilateral Salpingectomy with Oophorectomy
* Procedure: Biospecimen Collection
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration
* Procedure: Transvaginal Ultrasound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals 35-50 years of age, inclusive Patients who are undergoing risk-reducing salpingo-oophorectomy (RRSO) (for the BSO arm) and patients who have declined or elected to defer BSO after proper counselling to clearly explain the standard of care for BRCA1 mutation carriers and are undergoing salpingectomy (for the BLS arm with delayed oophorectomy arm). Concurrently planned hysterectomy with either arm is permitted At least one intact ovary and fallopian tube is in situ at the time of counseling and consent. Prior hysterectomy is allowed provided it did not include bilateral salpingectomy. Prior tubal ligation is allowed if one intact ovary and fallopian tube (with fimbria not removed) are present Positive Clinical Laboratory Improvement Act (CLIA)-approved test results for pathogenic or likely pathogenic germline BRCA1 mutation in the patient. Documentation of the result is required Patients may be premenopausal or menopausal Transvaginal ultrasound (TVUS) and CA-125 within 180 days of registration The patient or a legally authorized representative must provide study-specific informed consent prior to study entry Individuals who are currently pregnant or plan to become pregnant in the future through assisted reproductive technologies and who have received proper counseling are eligible. Individuals who are currently pregnant and plan bilateral salpingectomy at the time of a planned cesarean section are eligible. Patients must understand that they will not be able to become pregnant naturally in the future Exclusion Criteria: Individuals with a history of any prior cancer who have received chemotherapy within the past 30 days or radiotherapy to abdomen or pelvis at any prior time Prior history of ovarian cancer, including low malignant potential neoplasms (LMP), primary peritoneal carcinoma, or fallopian tube carcinoma Patients medically unfit for the planned surgical procedure Patients with abnormal screening tests (TVUS, CA-125) suspicious for occult or gross pelvic malignancy or neoplasm within the past 180 days An abnormal TVUS is defined as morphologic or structural variations suspicious for ovarian malignancy or complex cystic lesions (simple cysts < 5 cm in maximal diameter are not exclusionary) An abnormal CA-125 is defined as a level > 50 U/ml in premenopausal individuals if they are not current users of oral contraceptives; an abnormal CA-125 is defined as a level > 40 U/ml for premenopausal individuals who are current users of oral contraceptives. An abnormal CA-125 is defined as a level > 35 U/ml in postmenopausal individuals.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 50 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I (bilateral salpingectomy)<br>Patients undergo bilateral salpingectomy. Patients may then undergo oophorectomy after initial surgery. Patients also undergo a transvaginal ultrasound during screening and blood sample collection throughout the trial. | Procedure: Bilateral Salpingectomy<br>* Undergo bilateral salpingectomy<br>Procedure: Biospecimen Collection<br>* Undergo blood sample collection<br>* Other names: Specimen Collection;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>Procedure: Transvaginal Ultrasound<br>* Undergo transvaginal ultrasound<br>* Other names: TVU;|
| Active Comparator: Group II (bilateral salpingo-oophorectomy)<br>Patients undergo bilateral salpingo-oophorectomy. Patients also undergo a transvaginal ultrasound during screening and blood sample collection throughout the trial. | Procedure: Bilateral Salpingectomy with Oophorectomy<br>* Undergo bilateral salpingo-oophorectomy<br>* Other names: bilateral salpingo-oophorectomy;Procedure: Biospecimen Collection<br>* Undergo blood sample collection<br>* Other names: Specimen Collection;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>Procedure: Transvaginal Ultrasound<br>* Undergo transvaginal ultrasound<br>* Other names: TVU;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to development of incident high-grade serous carcinomas (HGSC), specifically ovarian, primary peritoneal, or fallopian tube cancers | Will be assessed using a stratified log rank test, stratifying for age. The effects of other covariates, such as familial history of gynecologic cancer, time to crossover for bilateral salpingectomy (BLS) patients, and age at study entry, will be adjusted for in Cox proportional hazard models. Patients who crossover will be analyzed according to the initial surgery received at study enrollment as this will reflect actual practice. | Up to 20 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health-related quality of life (QOL) | Will be measured by the Functional Assessment of Cancer Therapy - Endocrine Symptom (FACT-ES). The FACT total score (calculated from the physical, functional, social and emotional well-being subscales) and ES subscale will be assessed. Higher scores indicate better QOL for the FACT-ES and better functioning for the Female Sexual Function Index (FSFI) total score. | Up to 24 months post-surgery | 
| Cancer distress | Will be measured by the Impact of Events Scale (IES). | Up to 24 months post-surgery | 
| Medical decision making | Will be measured by the Shared Decision Making Questionnaire (SDM-Q-9) and, Decisional Regret Scale. The SDM-Q-9 total score and Decisional Regret Scale total score at each time point of collection will be compared between arms using a t-test with a significance level of 0.05. A linear model will be used to assess the association of the SDM-Q-9 total score with treatment arm and patient characteristics such as age and race. A similar model will be used to assess the association of the Decisional Regret Scale total score with treatment arm and patient characteristics such as age, race, crossover from BLS arm, and hysterectomy status. | Up to 24 months post-surgery | 
| Incidence of adverse events | Will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Counts and frequencies will be provided for the worst grade adverse event (AE) experienced by the patient by treatment arm. The distribution of AE grade in the BLS arm will be compared to the bilateral salpingo-oophorectomy arm using a chi-square test, or Fisher's exact test if cell frequencies are < 5, at the one-sided 0.05 significance level. | Up to 20 years | 
| Estrogen deprivation symptoms (pre-menopaused patients only) | Will be measured by the FACT-ES. The FACT total score (calculated from the physical, functional, social and emotional well-being subscales) and ES subscale will be assessed. Higher scores indicate better QOL for the FACT-ES and better functioning for the FSFI total score. Models will also include hormonal therapy as a covariate. | Up to 24 months post-surgery | 
| Sexual dysfunction (pre-menopausal patients only) | Will be measured by the FSFI. Higher scores indicate better functioning for the FSFI total score. | Up to 24 months post-surgery | 
| Menopausal symptoms (pre-menopausal patients only) | Will be measured by the Menopausal Symptom Checklist (MSCL). Models will also include hormonal therapy as a covariate. The MSCL total score and individual items will be compared between groups using the t-test and Wilcoxon test, respectively. The change from baseline in total score will be compared between groups at each follow-up time point. The change form baseline in the 3 items not included in the subscale scores will be compared between groups using the Wilcoxon test at each follow-up time point. | Up to 24 months post-surgery |