Risk-Reducing Surgery for Ovarian Cancer

Recruiting at 3 trial locations

Overseen By Roni Wilke, MD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Postmenopausal, Ovarian cancer, Legally incapable, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Varies based on individual treatment plan

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a prospective preference study that will evaluate non-inferiority of the innovative treatment (RRS with delayed RRO) as compared to the standard treatment (RRSO) with respect to high grade serous (ovarian) cancer incidence

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Risk-Reducing Salpingo-Oophorectomy (RRSO) for preventing ovarian cancer?

Research shows that Risk-Reducing Salpingo-Oophorectomy (RRSO) is highly effective in reducing the risk of ovarian and breast cancer in women with BRCA1 or BRCA2 mutations, making it a beneficial preventive treatment for those at high risk. ^{1 2 3 4 5}

Is risk-reducing surgery for ovarian cancer generally safe for humans?

Risk-reducing salpingo-oophorectomy (RRSO) is considered a safe intervention for preventing ovarian cancer in women at high risk, but it can lead to premature menopause, which may affect cognitive function and quality of life. ^{2 3 6 7 8}

How is the treatment Risk-Reducing Salpingo-Oophorectomy (RRSO) unique for ovarian cancer prevention?

Risk-Reducing Salpingo-Oophorectomy (RRSO) is unique because it is the most effective surgical option to significantly lower the risk of ovarian and breast cancer in women with BRCA1 or BRCA2 mutations, by removing the ovaries and fallopian tubes before cancer develops. ^{1 2 3 4 5}

Research Team

Roni Wilke, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for premenopausal women aged 25-50 with specific genetic mutations (BRCA1, BRCA2, BRIP1, RAD51C/D) who have completed childbearing and have at least one fallopian tube. It's not for those with a history of ovarian cancers or currently in cancer treatment.

Inclusion Criteria

I am within the age range specified for my specific genetic mutation.

Informed consent must be obtained and documented

I have at least one fallopian tube.

Exclusion Criteria

I am currently being treated for cancer.

I have had ovarian, fallopian tube, or peritoneal cancer.

I have had both of my fallopian tubes surgically removed.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo risk-reducing salpingectomy with delayed oophorectomy or risk-reducing salpingo-oophorectomy

Varies based on individual treatment plan

Follow-up

Participants are monitored for safety, ovarian cancer incidence, and other secondary outcomes

5-10 years

Exploratory Analysis

Estimate high grade serous (ovarian) cancer incidence for innovative and standard treatments in BRIP1, RAD51C, and RAD51D gene germline mutation carriers

Treatment Details

Interventions

• Risk-Reducing Oophorectomy-RRO
• Risk-Reducing Salpingectomy (RRS)
• Risk-Reducing Salpingo-Oophorectomy-RRSO

Trial Overview The study compares two preventive surgeries for high-risk women: immediate removal of fallopian tubes and ovaries (RRSO) versus just the tubes first then ovaries later (RRS with delayed RRO). The goal is to see if delaying ovary removal affects cancer incidence.

Participant Groups

Group I: Risk-Reducing Salpingo-Oophorectomy-RRSO Experimental Treatment 1 Intervention

Can help to lower the risk of ovarian cancer as well as the standard-of-care risk-reducing procedure involving the removal of the fallopian tubes and ovaries (risk-reducing salpingo-oophorectomy-RRSO)

Group II: Risk-Reducing Salpingectomy-RRS Experimental Treatment 1 Intervention

Can help to lower the risk of ovarian cancer with a delayed removal of 1.

Group III: Risk-Reducing Oophorectomy-RRO Experimental Treatment 1 Intervention

Can help to lower the risk of ovarian cancer removing both fallopian tubes.

Risk-Reducing Oophorectomy-RRO is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Risk-Reducing Oophorectomy for:

• Ovarian cancer prevention in high-risk individuals
• Breast cancer prevention in high-risk individuals

Approved in European Union as Risk-Reducing Oophorectomy for:

• Ovarian cancer prevention in high-risk individuals
• Breast cancer prevention in high-risk individuals

Approved in Canada as Risk-Reducing Oophorectomy for:

• Ovarian cancer prevention in high-risk individuals
• Breast cancer prevention in high-risk individuals

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

Risk-reducing salpingo-oophorectomy (RRSO) is cost-effective for preventing ovarian cancer in premenopausal women with a lifetime risk of 4% or higher, providing a life expectancy gain of 42.7 days at an incremental cost-effectiveness ratio (ICER) of £19,536 per quality-adjusted life-year (QALY).

The analysis suggests that RRSO remains cost-effective even at higher risk thresholds (up to 8.2% without hormone replacement therapy), indicating that current guidelines should be reconsidered to allow more at-risk women access to this preventive surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Specifying the ovarian cancer risk threshold of 'premenopausal risk-reducing salpingo-oophorectomy' for ovarian cancer prevention: a cost-effectiveness analysis. Manchanda, R., Legood, R., Antoniou, AC., et al.[2022]

A study involving 60 high-risk women aged 30 to 50 revealed that concerns about surgical menopause and loss of fertility are significant barriers to undergoing risk-reducing bilateral salpingo-oophorectomy (RRBSO), despite the understanding that it reduces ovarian cancer risk.

Participants expressed a strong desire for more information on managing the short- and long-term effects of surgical menopause, highlighting an unmet need for support and education in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring factors that impact uptake of risk-reducing bilateral salpingo-oophorectomy (RRBSO) in high-risk women. Hickey, M., Rio, I., Trainer, A., et al.[2021]

Laparoendoscopic single-site (LESS) risk-reducing salpingo-oophorectomy (RRSO) is a safe and feasible procedure for BRCA carriers and high-risk women, with no surgical complications reported in a study of 58 patients.

The procedure has favorable outcomes, including a mean operative time of 38.1 minutes and minimal postoperative pain, making it suitable for patients undergoing active cancer treatment, as it allows for a quicker recovery and less disruption to ongoing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-port risk-reducing salpingo-oophorectomy with and without hysterectomy: surgical outcomes and learning curve analysis. Escobar, PF., Starks, DC., Fader, AN., et al.[2010]

Risk-reducing salpingo-oophorectomy (RRSO) significantly lowers the risk of breast cancer in women with BRCA1/2 mutations, with a hazard ratio of 0.49, indicating nearly a 51% reduction in risk.

RRSO also greatly reduces the risk of ovarian or fallopian tube cancer in BRCA1/2 mutation carriers, with a hazard ratio of 0.21, suggesting a 79% reduction in risk, making it a crucial option for cancer prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. Rebbeck, TR., Kauff, ND., Domchek, SM.[2022]

In a study of 580 BRCA1/2 mutation carriers, the uptake of risk-reducing salpingo-oophorectomy (RRSO) was extremely high, with 98.5% of BRCA1 and 97.5% of BRCA2 carriers opting for the surgery, often before the age of 40 or 45, respectively.

The high uptake of RRSO is likely due to effective counseling at the Family Cancer Clinic, highlighting the need for future research to address the long-term health impacts of premature surgical menopause, potentially through improved hormone replacement therapy or alternative strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Very high uptake of risk-reducing salpingo-oophorectomy in BRCA1/2 mutation carriers: A single-center experience. Harmsen, MG., Arts-de Jong, M., Horstik, K., et al.[2022]

In a study of 644 women undergoing risk-reducing salpingo-oophorectomy (RRSO), 2.6% were found to have occult neoplasms, with a higher occurrence in BRCA1 carriers, particularly those aged 45 and older, indicating a significant risk for this group.

The study highlights the importance of serial sectioning during RRSO to detect hidden cancers, as it revealed that 88.2% of the occult neoplasms were located in the fallopian tubes, emphasizing the need for thorough examination in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathologic findings and clinical outcomes in women undergoing risk-reducing surgery to prevent ovarian and fallopian tube carcinoma: A large prospective single institution experience. Rush, SK., Swisher, EM., Garcia, RL., et al.[2020]

In a study of 57 premenopausal women at high risk for ovarian cancer, those who underwent risk-reducing bilateral salpingo-oophorectomy (RRSO) experienced a significant decline in perceived cognitive impairment within the first 6 months post-surgery, regardless of hormone therapy use.

While hormone therapy did not significantly impact cognitive scores, it was noted that sleep disruption was common after RRSO and was not alleviated by hormone therapy, indicating a need for further support in managing menopausal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term impact of surgically induced menopause on cognitive function and wellbeing in women at high risk for ovarian cancer following risk-reducing bilateral salpingo-oophorectomy. Chang, H., Kamara, D., Bresee, C., et al.[2021]

A study of 301 Norwegian women who underwent risk-reducing salpingo-oophorectomy (RRSO) found that their quality of life (QoL) and fatigue levels were similar to those of age-matched women from the general population, indicating that RRSO does not negatively impact these aspects of life.

Women who had a cancer diagnosis prior to RRSO reported significantly lower QoL and higher fatigue compared to those without a cancer history, suggesting that the effects of prior cancer may overshadow the benefits of the surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatigue and quality of life after risk-reducing salpingo-oophorectomy in women at increased risk for hereditary breast-ovarian cancer. Michelsen, TM., Dørum, A., Tropé, CG., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Specifying the ovarian cancer risk threshold of 'premenopausal risk-reducing salpingo-oophorectomy' for ovarian cancer prevention: a cost-effectiveness analysis. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Exploring factors that impact uptake of risk-reducing bilateral salpingo-oophorectomy (RRBSO) in high-risk women. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Single-port risk-reducing salpingo-oophorectomy with and without hysterectomy: surgical outcomes and learning curve analysis. [2010]

4. United States pubmed.ncbi.nlm.nih.gov

Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Very high uptake of risk-reducing salpingo-oophorectomy in BRCA1/2 mutation carriers: A single-center experience. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Pathologic findings and clinical outcomes in women undergoing risk-reducing surgery to prevent ovarian and fallopian tube carcinoma: A large prospective single institution experience. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Short-term impact of surgically induced menopause on cognitive function and wellbeing in women at high risk for ovarian cancer following risk-reducing bilateral salpingo-oophorectomy. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Fatigue and quality of life after risk-reducing salpingo-oophorectomy in women at increased risk for hereditary breast-ovarian cancer. [2019]