Clinical trial NCT02760849: Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
Official title: WISP (Women Choosing Surgical Prevention)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Deleterious BARD1 Gene Mutation
Deleterious BRCA1 Gene Mutation
Deleterious BRCA2 Gene Mutation
Deleterious BRIP1 Gene Mutation
Deleterious EPCAM Gene Mutation
Deleterious MLH1 Gene Mutation
Deleterious MSH2 Gene Mutation
Deleterious MSH6 Gene Mutation
Deleterious PALB2 Gene Mutation
Deleterious PMS2 Gene Mutation
Deleterious RAD51C Gene Mutation
Deleterious RAD51D Gene Mutation
Hereditary Breast and Ovarian Cancer Syndrome
Premenopausal
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2016-05-04
Enrollment: 374
Sex: FEMALE
Minimum age (years): 30
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This phase II trial studies how well surgery works in preventing ovarian cancer in patients with genetic mutations at risk of ovarian cancer. Risk reducing salpingo oophorectomy (RRSO) is surgery to remove the fallopian tubes and ovaries at the same time. Interval salpingectomy with delayed oophorectomy (ISDO) is surgery to remove the fallopian tubes. It is not known whether ISDO works better than RRSO at lowering risk of ovarian cancer and improving the sexual function and psychosocial well-being in patients with genetic mutation.

Detailed description: Primary Objectives:

1. To examine changes in female sexual function with the strategy of interval salpingectomy and delayed oophorectomy (ISDO) compared to the strategy of risk-reducing salpingo-oophorectomy (RRSO) for patients who carry genetic mutations that predispose them to ovarian cancer.

Secondary Objectives:

1. To estimate the onset and severity of menopausal symptoms with ISDO compared to RRSO.
2. To estimate quality of life with ISDO compared to RRSO.
3. To examine participants' satisfaction level and cancer worry level with their choice of prophylactic procedures.
4. To estimate the impact of ISDO compared to RRSO on mental health, including depression, anxiety, and sleep quality.
5. To determine the compliance with delayed oophorectomy within the ISDO arm.
6. To estimate the number of fallopian tube, ovarian, primary peritoneal malignancies and other malignancies over the course of the study.
7. To identify common themes regarding influential factors in the decision to undergo risk reducing surgery in premenopausal women at genetic high-risk for ovarian can

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I: Patients undergo ISDO.

ARM II: Patients undergo RRSO.

After completion of study treatment, patients are followed up at 1 and 6 months, 1 year, and 2 years.

Eligibility criteria: Inclusion Criteria:

1. Women must be ≥ 30 and ≤ 50 years of age.
2. Premenopausal women with a documented deleterious mutation in one of the following ovarian cancer genes: BRCA1, BRCA2, BRIP1, PALB2, RAD51C, RAD51D, BARD1, MSH2, MSH6, MLH1, PMS2, or EPCAM. Menopause is defined as ≥ 12 months of amenorrhea. However, for those patients with ≥ 12 months of amenorrhea who may be pre-menopausal, levels of FSH, LH, and estradiol in the pre-menopausal range will be acceptable.
3. Willing to undergo two surgical procedures (if chooses the ISDO arm).
4. Presence of at least 1 fallopian tube and 1 ovary. Prior unilateral salpingectomy is allowed; prior bilateral salpingectomy is not allowed
5. Patients who have undergone a prior tubal ligation will be eligible.
6. Participants may have a personal history of non-ovarian malignancy, but must:

   1. Be without evidence of disease at enrollment
   2. Remain premenopausal
   3. Have completed treatment (including surgery, chemotherapy, radiotherapy or hormonal therapy) \> 3 months prior to enrollment (other than non-melanoma skin cancer)
7. Willingness to return to the enrolling site for the study surgical procedures, including pre-operative and post-operative care.

   Patients in the ISDO arm must be willing to return to the enrolling site for yearly ovarian cancer assessment.
8. Patients must understand that they will be permanently sterilized

Exclusion Criteria:

1. Women with a personal history of ovarian, fallopian tube, or primary peritoneal cancer.
2. Current treatment with Tamoxifen or Aromatase Inhibitors.
3. Medical comorbidities making surgery unsafe as determined by the patient's surgeon.
4. Women who are pregnant or post-partum (within 3 months of delivery).

   * Patients are deemed not pregnant by virtue of urine pregnancy test (UPT), transvaginal ultrasound, beta HCG, or best judgment of the investigator. Pregnancy testing is not required per protocol to determine study eligibility.
   * Women who become pregnant on the ISDO arm via reproductive technology can remain on study. However, data collection will be suspended during pregnancy and 3 months post-partum.
5. Women with elevated levels of CA125 (\>50) or transvaginal ultrasound suggesting cancer, unless findings are consistent with endometriosis. CA125 and transvaginal ultrasounds must be the most recent, but no older than 1 year from the date of enrollment.
6. Inability to provide informed consent.
7. Inability to read or speak English.

Primary outcomes:
measure: Percent of women with clinically meaningful change in the Female Sexual Function Index (FSFI) score
timeFrame: From baseline to 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Washington University
state: Missouri
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center at NYU Langone
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania/Abramson Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Roni N Wilke, MD
role: PRINCIPAL_INVESTIGATOR
References: