Salpingectomy with Delayed Oophorectomy for Ovarian Cancer

Not currently recruiting at 1 trial location

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Postmenopausal, No BRCA mutation, Ovarian cancer, others

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

Compensation: Varies

Number of Visits: 13

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new methods to prevent ovarian cancer in women with specific BRCA gene mutations, which increase their risk. It compares regular screening, full removal of fallopian tubes and ovaries, and a two-step surgery called Prophylactic Salpingectomy with Delayed Oophorectomy. In this two-step surgery, only the fallopian tubes are removed first, delaying ovary removal to avoid early menopause. The trial aims to assess how these approaches affect cancer risk and safety. Women with a BRCA mutation who are at high risk for ovarian cancer, especially those who are premenopausal and considering permanent sterilization, might be suitable candidates. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could shape future prevention strategies.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it allows for the use of SERMs (selective estrogen receptor modulators) or aromatase inhibitors, so you may be able to continue these if applicable.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Prophylactic Salpingectomy with Delayed Oophorectomy (PSDO) might involve risks, such as requiring two surgeries and possibly not reducing ovarian cancer risk. However, many women find these risks acceptable. The main benefit of PSDO is that it allows women to retain their ovaries longer, delaying menopause and its effects.

In contrast, studies have demonstrated that Risk-Reducing Salpingo-Oophorectomy (RRSO) effectively lowers ovarian cancer risk for women with BRCA gene mutations. This procedure, which involves removing both the fallopian tubes and ovaries, is well-documented for its effectiveness in reducing cancer risk. However, it induces immediate menopause, which can lead to various side effects.

Both PSDO and RRSO are outpatient surgeries, allowing patients to typically return home the same day. Safety data is more established for RRSO, showing it is generally well-tolerated. PSDO is newer, so there is less long-term data, but it is considered safe with known risks. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores innovative strategies for reducing the risk of ovarian cancer in women with BRCA gene mutations. Unlike the standard approach of immediate risk-reducing salpingo-oophorectomy (RRSO), this trial examines the potential benefits of a prophylactic salpingectomy with delayed oophorectomy (PSDO), which may help maintain hormonal balance and quality of life by delaying the removal of ovaries. Additionally, the trial includes an arm focusing on regular ovarian cancer screening, which could provide crucial insights into early detection methods. These approaches aim to offer more personalized and less invasive options for high-risk women, potentially transforming how we manage genetic risks for ovarian cancer.

What evidence suggests that this trial's treatments could be effective for reducing the risk of ovarian cancer?

Research has shown that Risk-Reducing Salpingo-Oophorectomy (RRSO), a treatment option in this trial, effectively lowers the risk of ovarian cancer in women with BRCA gene mutations. Studies indicate that RRSO significantly reduces the risks of both ovarian and breast cancer. In contrast, Prophylactic Salpingectomy with Delayed Oophorectomy (PSDO), another treatment option, is still under investigation. Currently, no evidence supports that removing only the fallopian tubes lowers the risk of ovarian cancer, though many women express interest in this option. The third approach, ovarian cancer screening, involves regular tests to detect signs of cancer but does not directly reduce the risk of developing it. The effectiveness of each approach varies, with RRSO being well-proven and PSDO requiring further research. ^{4 6 7 8 9}

Who Is on the Research Team?

Denise Nebgen, MD, PHD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for premenopausal women aged 30-47 with a BRCA1 or BRCA2 mutation, who are candidates for surgery and desire permanent sterilization. They must be willing to undergo two surgeries if choosing the PSDO arm and have completed any cancer treatments at least 3 months prior.

Inclusion Criteria

Willingness to return to the enrolling site for ovarian cancer screening during the study period.

I am a woman between 30 and 48 years old.

I had cancer other than ovarian, am now cancer-free, and finished treatment over 3 months ago.

Exclusion Criteria

Women who are pregnant. Patients are deemed not pregnant by virtue of urine pregnancy test (UPT), transvaginal ultrasound, beta HCG, or best judgement of the investigator. Pregnancy testing is not required per protocol to determine study eligibility.

Inability to provide informed consent.

Women whose most recent CA125 blood test or transvaginal ultrasound is not normal. If your most recent test is normal, then you can still participate even if you had abnormal tests in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Ovarian Cancer Screening

Participants undergo physical exams, blood tests, and ultrasounds every 6 months for up to 3 years to screen for ovarian cancer.

3 years

Every 6 months

Prophylactic Salpingectomy with Delayed Oophorectomy (PSDO)

Participants undergo salpingectomy as an outpatient procedure, followed by regular ovarian cancer screening until delayed oophorectomy.

3 years

Regular follow-ups every 6 months

Risk-Reducing Salpingo-Oophorectomy (RRSO)

Participants undergo RRSO as an outpatient procedure, with follow-up visits to monitor recovery and discuss pathology results.

1 year

1 day, 1 week, 1 month, 6 months, and 1 year post-surgery

Follow-up

Participants are monitored annually for changes in medical history after the last study visit.

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Prophylactic Salpingectomy with Delayed Oophorectomy

Trial Overview The study compares ovarian cancer screening methods with two surgical procedures: risk-reducing salpingo-oophorectomy (RRSO) where both fallopian tubes and ovaries are removed, and prophylactic salpingectomy with delayed oophorectomy (PSDO), which removes fallopian tubes first, delaying ovary removal.

How Is the Trial Designed?

Group I: Risk-Reducing Salpingo-Oophorectomy (RRSO) Experimental Treatment 4 Interventions

Woman who have a mutation (genetic change) in one of the BRCA genes, and are at high risk for developing ovarian cancer have risk-reducing salpingo-oophorectomy (RRSO) performed as an outpatient procedure.

Group II: Prophylactic Salpingectomy with Delayed Oophorectomy (PSDO) Experimental Treatment 4 Interventions

Woman who have a mutation (genetic change) in one of the BRCA genes, and are at high risk for developing ovarian cancer have salpingectomy performed as an outpatient procedure. After the 3-year follow up period, oophorectomy performed as an outpatient procedure.

Group III: Ovarian Cancer Screening Experimental Treatment 4 Interventions

Woman who have a mutation (genetic change) in one of the BRCA genes, and are at high risk for developing ovarian cancer will return to clinic every six months to undergo screening for ovarian cancer symptoms, physical examination, CA125, HE4, and transvaginal ultrasound.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

Risk-reducing salpingo-oophorectomy is the only proven intervention that significantly decreases mortality from ovarian cancer in women at increased risk, making it the standard care for risk reduction.

For high-risk premenopausal women, prophylactic salpingectomy followed by delayed oophorectomy is recommended for consideration in clinical trials, suggesting a potential alternative approach to managing ovarian cancer risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Options in Prophylactic Surgery to Prevent Ovarian Cancer in High-Risk Women: How New Hypotheses of Fallopian Tube Origin Influence Recommendations. Swanson, CL., Bakkum-Gamez, JN.[2018]

Women with BRCA1/2 pathogenic variants experience better menopause-related quality of life after risk-reducing salpingectomy (RRS) compared to risk-reducing salpingo-oophorectomy (RRSO), with a significant difference in climacteric symptoms observed in a study of 577 women.

The study found that even with hormone replacement therapy, RRS resulted in fewer menopause-related symptoms than RRSO, suggesting that RRS may be a preferable option for women seeking to delay menopause while managing cancer risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Salpingectomy With Delayed Oophorectomy Versus Salpingo-oophorectomy With Quality of Life in BRCA1/2 Pathogenic Variant Carriers: A Nonrandomized Controlled Trial. Steenbeek, MP., Harmsen, MG., Hoogerbrugge, N., et al.[2022]

Radical fimbriectomy followed by delayed oophorectomy is a safe and well-tolerated alternative for high-risk women who refuse the standard risk-reducing salpingo-oophorectomy, with no cases of pelvic invasive cancer reported after a median follow-up of 7.3 years.

The study found that while two cases of occult neoplasia were identified, the overall safety profile was strong, with only minor intraoperative complications and no significant postoperative issues, making this approach a viable option to avoid early menopause.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic Radical Fimbriectomy with Delayed Oophorectomy in Women with a High Risk of Developing an Ovarian Carcinoma: Results of a Prospective National Pilot Study. Leblanc, E., Narducci, F., Ferron, G., et al.[2023]

The study aims to determine if salpingectomy with delayed oophorectomy is as effective as the standard salpingo-oophorectomy in preventing tubo-ovarian cancer in individuals with high inherited risk, specifically BRCA1 and BRCA2 mutation carriers.

This international trial will involve 3000 participants and is designed to assess cancer incidence by comparing outcomes over a follow-up period of at least 10 years, with results expected by 2036.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TUBectomy with delayed oophorectomy as an alternative to risk-reducing salpingo-oophorectomy in high-risk women to assess the safety of prevention: the TUBA-WISP II study protocol. Steenbeek, MP., van Bommel, MHD., intHout, J., et al.[2023]

The study aims to evaluate the impact of risk-reducing early salpingectomy with delayed oophorectomy on sexual function in pre-menopausal women at increased risk of tubo-ovarian cancer, involving 1000 participants across three groups: early salpingectomy, standard salpingo-oophorectomy, and controls.

The hypothesis suggests that early salpingectomy will be non-inferior or superior in terms of sexual and endocrine function compared to standard surgery, potentially offering a safer alternative that avoids premature menopause and its associated health risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventing Ovarian Cancer through early Excision of Tubes and late Ovarian Removal (PROTECTOR): protocol for a prospective non-randomised multi-center trial. Gaba, F., Robbani, S., Singh, N., et al.[2023]

The review included seven randomized controlled trials with 350 women, but found no studies reporting on the incidence of ovarian cancer after hysterectomy with opportunistic salpingectomy compared to without, indicating a gap in research on this preventive measure.

There was insufficient data to determine differences in surgical adverse events or postoperative hormonal status between the two groups, suggesting that while opportunistic salpingectomy may be safe, its long-term effects, especially on ovarian reserve, need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hysterectomy with opportunistic salpingectomy versus hysterectomy alone. van Lieshout, LAM., Steenbeek, MP., De Hullu, JA., et al.[2022]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK1247/

BRCA1- and BRCA2-Associated Hereditary Breast and ... - NCBI A prospective cohort study of 2,482 women with BRCA1 or BRCA2 pathogenic variants reported a 79% reduction in ovarian cancer mortality and a 60% ...

2. cancer.gov cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet

BRCA Gene Changes: Cancer Risk and Genetic Testing Ovarian cancer: About 39%–58% of women who inherit a harmful change in BRCA1 and 13%–29% of women who inherit a harmful change in BRCA2 will ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090825825009485

Ovarian cancer after breast cancer in women with a ... Among BRCA1 carriers, the risk was 12.2 % in women with breast cancer and 32.0 % in those without. Among BRCA2 carriers, the 15-year ovarian cancer risk was 2.0 ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2839003

Estimands for Clinical Effectiveness of Risk-Reducing Early ...  BRCA1 and BRCA2 PV carriers have an approximate 44% and 17% lifetime OC risk, respectively. ... Risk-reducing salpingo-oophorectomy (RRSO) is ...

5. nature.com nature.com/articles/s41416-019-0484-8

Cancer screening and prevention in BRCA mutation carriers Ultimately, the risk of breast cancer in those at 70 years of age with a BRCA mutation is in the order of 45–65% and the risk of contralateral ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.34.15_suppl.1506

Feasibility study in women with BRCA mutations. However, no data exist to demonstrate whether salpingectomy lowers the risk of developing ovarian cancer (OC) in women with BRCA mutations. We ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4035022/

Acceptability of Prophylactic Salpingectomy with Delayed ... Acceptable study risks included the need for two surgeries (77.2%), possibility of not lowering ovarian cancer risk (68%), and disruption of ovarian blood ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090825814001486

Acceptability of prophylactic salpingectomy with delayed ... Acceptable study risks included the need for two surgeries (77.2%), possibility of not lowering ovarian cancer risk (68%), and disruption of ovarian blood ...

9. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00156-1/fulltext

Long-term health outcomes of bilateral salpingo ... Women with pathogenic variants in BRCA1 and BRCA2 have a high risk of developing ovarian and breast cancer. By age 80 years, the risk for breast ...