Tubectomy with Delayed Oophorectomy for Ovarian Cancer Prevention

(TUBA-WISP-II Trial)

Recruiting at 36 trial locations

Overseen By Joanne A. de Hullu, MD, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: University Medical Center Nijmegen

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: 4

3000 Participants Needed

Trial Summary

What is the purpose of this trial?

The aim of the project is to evaluate the risk-reducing salpingectomy with delayed oophorectomy as an alternative for risk-reducing salpingo-oophorectomy in high risk women with respect to 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 Tubectomy with Delayed Oophorectomy for Ovarian Cancer Prevention?

Research suggests that removing the fallopian tubes (salpingectomy) while delaying the removal of the ovaries (oophorectomy) may help reduce the risk of ovarian cancer in women with BRCA1/2 mutations, potentially delaying menopause and its associated health issues. However, while this approach is considered promising, it is still under investigation and not yet proven to be as effective as the current standard, which involves removing both the fallopian tubes and ovaries (RRSO). ^{1 2 3 4 5}

Is the procedure of tubectomy with delayed oophorectomy generally safe for humans?

The procedure of bilateral salpingectomy with delayed oophorectomy has been studied for safety and acceptability in women with BRCA mutations, suggesting it may be a safe option, although it is still considered investigational and not yet proven for clinical use. ^{1 3 4 6 7}

How does the treatment 'Tubectomy with Delayed Oophorectomy' differ from other treatments for ovarian cancer prevention?

This treatment involves removing the fallopian tubes first and delaying the removal of the ovaries, which can help prevent early menopause and its associated health issues. It is different from the standard approach, which removes both the fallopian tubes and ovaries at the same time, often leading to premature menopause. ^{1 5 8 9 10}

Research Team

Elizabeth Swisher, MD

Principal Investigator

University of Washington

Karen H. Lu, MD

Principal Investigator

M.D. Anderson Cancer Center

Joanne A. de Hullu, MD, PhD

Principal Investigator

Radboud University Medical Center

Rosella P.M.G. Hermens, MD,PhD

Principal Investigator

Radboud University Medical Center

Eligibility Criteria

This trial is for women aged 25-50 with a high-risk gene mutation (BRCA1, BRCA2, RAD51C, RAD51D, or BRIP1) who have finished having children and still have at least one fallopian tube. Women with a history of non-ovarian cancer can join if they give informed consent.

Inclusion Criteria

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

Childbearing completed

Informed consent must be obtained and documented according to national and local regulatory requirements and the local rules followed in the institution.

Exclusion Criteria

I have had both of my fallopian tubes surgically removed.

I am not legally able to make my own decisions.

I plan to have a second surgery within two years after my first.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Risk-reducing Salpingectomy

Participants undergo risk-reducing salpingectomy after the completion of childbearing

6 weeks

1 visit (in-person) for surgery

Delayed Oophorectomy

Participants undergo delayed oophorectomy as part of the experimental strategy

6 weeks

1 visit (in-person) for surgery

Follow-up

Participants are monitored for safety and effectiveness after each surgery

6 weeks after each surgery

2 visits (in-person)

Treatment Details

Interventions

• Risk-reducing salpingectomy with delayed oophorectomy
• Risk-reducing salpingo-oophorectomy

Trial Overview The study compares two preventive surgeries in high-risk women: removing the fallopian tubes first and ovaries later versus removing both at once. The goal is to see if delaying ovary removal lowers ovarian cancer risk without immediate menopause.

Participant Groups

Group I: Risk-reducing salpingectomy with delayed oophorectomy Experimental Treatment 1 Intervention

Risk-reducing salpingectomy after the completion of childbearing with delayed oophorectomy.

Group II: Risk-reducing salpingo-oophorectomy Active Control 1 Intervention

Risk-reducing salpingo-oophorectomy.

Risk-reducing salpingectomy with delayed oophorectomy is already approved in European Union, United States for the following indications:

Approved in European Union as Risk-reducing salpingectomy with delayed oophorectomy for:

• Ovarian cancer prevention in high-risk women

Approved in United States as Risk-reducing salpingectomy with delayed oophorectomy for:

• Ovarian cancer prevention in high-risk women

Who Is Running the Clinical Trial?

University Medical Center Nijmegen

Lead Sponsor

Trials

49

Recruited

250,000+

Findings from Research

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]

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]

Risk-reducing salpingo-oophorectomy (RRSO) is the most effective surgical option for reducing ovarian cancer risk in women with BRCA1/2 mutations, but for those not ready for this surgery, bilateral salpingectomy with ovarian retention (BSOR) may serve as a temporary alternative.

While BSOR could be a potential risk-reducing strategy, it is currently considered investigational and may not provide the same protective benefits against breast cancer as RRSO, highlighting the need for further clinical trials to evaluate its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does bilateral salpingectomy with ovarian retention warrant consideration as a temporary bridge to risk-reducing bilateral oophorectomy in BRCA1/2 mutation carriers? Greene, MH., Mai, PL., Schwartz, PE.[2022]

In a pilot study involving 43 pre-menopausal BRCA1/2 mutation carriers, those who underwent bilateral salpingectomy with delayed oophorectomy (BS/DO) experienced no surgical complications and reported high satisfaction with their choice of procedure.

Patients who chose BS/DO showed significant reductions in cancer worry and anxiety levels 12 months post-surgery, indicating that this approach may be a psychologically beneficial alternative to immediate risk-reducing salpingo-oophorectomy (RRSO).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral salpingectomy with delayed oophorectomy for ovarian cancer risk reduction: A pilot study in women with BRCA1/2 mutations. Nebgen, DR., Hurteau, J., Holman, LL., et al.[2022]

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]

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]

In a study of 20 hysterectomy specimens simulating risk-reducing bilateral salpingo-oophorectomy (RRSO), 73% of the uterine cornual sites had residual tubal remnants, indicating that RRSO may not completely remove all tubal epithelium.

Each identified tubal remnant contained preserved columnar epithelium, with a median length of 6 mm and a median surface area of 14 mm², raising questions about the potential clinical implications of these remnants in relation to tubal cancer risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does risk-reducing bilateral salpingo-oophorectomy leave behind residual tube? Cass, I., Walts, A., Karlan, BY.[2010]

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]

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 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]

References

1. United States 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. [2022]

2. 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]

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

Does bilateral salpingectomy with ovarian retention warrant consideration as a temporary bridge to risk-reducing bilateral oophorectomy in BRCA1/2 mutation carriers? [2022]

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

Bilateral salpingectomy with delayed oophorectomy for ovarian cancer risk reduction: A pilot study in women with BRCA1/2 mutations. [2022]

5. United States 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. [2018]

6. 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]

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

Does risk-reducing bilateral salpingo-oophorectomy leave behind residual tube? [2010]

8. England 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. [2023]

9. Switzerland 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. [2023]

10. England 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. [2023]