A Study to Compare Two Surgical Procedures in Women With BRCA1 Mutations to Assess Reduced Risk of Ovarian Cancer
A Study to Compare Two Surgical Procedures in Women With BRCA1 Mutations to Assess Reduced Risk of Ovarian Cancer
This trial studies how well two surgical procedures (bilateral salpingectomy and bilateral
 salpingo-oophorectomy) work in reducing the risk of ovarian cancer for women 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.
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 women
 with deleterious BRCA1 germline mutations.

 SECONDARY OBJECTIVES:

 I. To prospectively assess estrogen deprivation symptoms in BLS patients as measured by the
 Functional Assessment of Cancer Therapy - Endocrine Symptom (FACT-ES) subscale compared to
 women 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]),
 sexual dysfunction (Female Sexual Function Index [FSFI]), and cancer distress (Impact of
 Events Scale [IES]) in women who have undergone BLS, in comparison to normative data
 (MSCL/FACT-ES) and data from BSO patients.

 III. 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.

 IV. 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.

 II. To estimate the cost-effectiveness of BLS compared to BSO for ovarian cancer risk
 reduction.

 III. To determine the association between health related (HR)-QOL with menopausal symptoms,
 as measured by the MSCL, sexual dysfunction, as measured by FSFI/PROMIS screener and external
 sexual function items, and cancer distress as measured by the IES.

 IV. 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 (pending funding).

 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.

 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.
Inclusion Criteria:

 -  Patients who have declined or elected to defer risk-reducing salpingo-oophorectomy
 (RRSO) after proper counselling to clearly explain the standard of care for BRCA1
 mutation carriers (for the BLS with delayed oophorectomy arms) or patients who are
 undergoing RRSO (for the RRSO arm)

 -  At least one intact ovary and fallopian tube

 -  Positive Clinical Laboratory Improvement Act (CLIA)-approved test results for
 pathogenic or likely pathogenic germline BRCA1 mutation in the patient herself.
 Documentation of the result is required

 -  Premenopausal; defined as < 12 months of amenorrhea. However, for those patients with
 >= 12 months of amenorrhea who may be pre-menopausal or patients with a prior
 hysterectomy with at least one retained ovary/tube, levels of follicle stimulating
 hormone (FSH), luteinizing hormone (LH), and in the premenopausal range per local
 institutional standards will be acceptable

 -  Concurrently planned or prior hysterectomy is permitted as long as at least one
 fallopian tube and one ovary had been retained

 -  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

 -  Patient must have negative urine pregnancy test within 14 days prior to registration
 based on local institutional policies

 Exclusion Criteria:

 -  Women with a history of any prior cancer who have received chemotherapy within the
 past 12 months, hormonal therapy in the past 90 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 this study population of
 premenopausal women if they are not current users of oral contraceptives; an
 abnormal CA-125 is defined as a level > 40 U/ml for premenopausal women who are
 current users of oral contraceptives

 -  Women who are currently pregnant or plan to become pregnant in the future