Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations

M.D. Anderson Cancer Center

Status: Active, not recruiting

Conditions: Deleterious BRIP1 Gene Mutation; Deleterious MSH6 Gene Mutation; Deleterious RAD51C Gene Mutation; Deleterious MSH2 Gene Mutation; Deleterious RAD51D Gene Mutation; Deleterious PMS2 Gene Mutation; Deleterious BARD1 Gene Mutation; Deleterious BRCA2 Gene Mutation; Deleterious MLH1 Gene Mutation; Hereditary Breast and Ovarian Cancer Syndrome; Deleterious BRCA1 Gene Mutation; Deleterious EPCAM Gene Mutation; Deleterious PALB2 Gene Mutation; Premenopausal

Treatments: Procedure: Salpingectomy; Procedure: Salpingo-Oophorectomy; Other: Quality-of-Life Assessment; Procedure: Oophorectomy; Other: Laboratory Biomarker Analysis

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02760849

2015-0814 (Other Identifier)

NCI-2016-00778 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 374 patients

Sex: Female

Ages: 30 to 50 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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374 participants in 2 patient groups

Arm I (ISDO)

Experimental group

Description:

Patients undergo ISDO.

Treatment:

Other: Laboratory Biomarker Analysis

Procedure: Oophorectomy

Other: Quality-of-Life Assessment

Procedure: Salpingectomy

Arm II (RRSO)

Active Comparator group

Description:

Patients undergo RRSO.

Treatment:

Other: Laboratory Biomarker Analysis

Procedure: Salpingo-Oophorectomy

Other: Quality-of-Life Assessment