A Study to Compare Two Surgical Procedures in Individuals With BRCA1 Mutations to Assess Reduced Risk of Ovarian Cancer

• ClinicalTrials.gov Identifier: NCT04251052
• Recruitment Status: Recruiting
• First Posted: January 31, 2020
• Last Update Posted: February 17, 2023
• Sponsor: NRG Oncology
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): NRG Oncology

Tracking Information

• First Submitted Date: January 14, 2020
• First Posted Date: January 31, 2020
• Last Update Posted Date: February 17, 2023
• Actual Study Start Date: June 23, 2020
• Estimated Primary Completion Date: June 23, 2036 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 30, 2020)

Time to development of incident high-grade serous carcinomas (HGSC), specifically ovarian, primary peritoneal, or fallopian tube cancers [ Time Frame: Up to 20 years ]

Will be assessed using a stratified log rank test, stratifying for age. The effects of other covariates, such as familial history of gynecologic cancer, time to crossover for bilateral salpingectomy (BLS) patients, and age at study entry, will be adjusted for in Cox proportional hazard models. Patients who crossover will be analyzed according to the initial surgery received at study enrollment as this will reflect actual practice.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 15, 2023)

• Health-related quality of life (QOL) [ Time Frame: Up to 24 months post-surgery ]
  Will be measured by the Functional Assessment of Cancer Therapy - Endocrine Symptom (FACT-ES). The FACT total score (calculated from the physical, functional, social and emotional well-being subscales) and ES subscale will be assessed. Higher scores indicate better QOL for the FACT-ES and better functioning for the Female Sexual Function Index (FSFI) total score.
• Cancer distress [ Time Frame: Up to 24 months post-surgery ]
  Will be measured by the Impact of Events Scale (IES).
• Medical decision making [ Time Frame: Up to 24 months post-surgery ]
  Will be measured by the Shared Decision Making Questionnaire (SDM-Q-9) and, Decisional Regret Scale. The SDM-Q-9 total score and Decisional Regret Scale total score at each time point of collection will be compared between arms using a t-test with a significance level of 0.05. A linear model will be used to assess the association of the SDM-Q-9 total score with treatment arm and patient characteristics such as age and race. A similar model will be used to assess the association of the Decisional Regret Scale total score with treatment arm and patient characteristics such as age, race, crossover from BLS arm, and hysterectomy status.
• Incidence of adverse events [ Time Frame: Up to 20 years ]
  Will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Counts and frequencies will be provided for the worst grade adverse event (AE) experienced by the patient by treatment arm. The distribution of AE grade in the BLS arm will be compared to the bilateral salpingo-oophorectomy arm using a chi-square test, or Fisher's exact test if cell frequencies are < 5, at the one-sided 0.05 significance level.
• Estrogen deprivation symptoms (pre-menopaused patients only) [ Time Frame: Up to 24 months post-surgery ]
  Will be measured by the FACT-ES. The FACT total score (calculated from the physical, functional, social and emotional well-being subscales) and ES subscale will be assessed. Higher scores indicate better QOL for the FACT-ES and better functioning for the FSFI total score. Models will also include hormonal therapy as a covariate.
• Sexual dysfunction (pre-menopausal patients only) [ Time Frame: Up to 24 months post-surgery ]
  Will be measured by the FSFI. Higher scores indicate better functioning for the FSFI total score.
• Menopausal symptoms (pre-menopausal patients only) [ Time Frame: Up to 24 months post-surgery ]
  Will be measured by the Menopausal Symptom Checklist (MSCL). Models will also include hormonal therapy as a covariate. The MSCL total score and individual items will be compared between groups using the t-test and Wilcoxon test, respectively. The change from baseline in total score will be compared between groups at each follow-up time point. The change form baseline in the 3 items not included in the subscale scores will be compared between groups using the Wilcoxon test at each follow-up time point.

Original Secondary Outcome Measures (submitted: January 30, 2020)

• Health-related quality of life (QOL) [ Time Frame: Up to 24 months post-surgery ]
  Will be measured by the Functional Assessment of Cancer Therapy - Endocrine Symptom (FACT-ES). The FACT total score (calculated from the physical, functional, social and emotional well-being subscales) and ES subscale will be assessed. Higher scores indicate better QOL for the FACT-ES and better functioning for the FSFI total score.
• Estrogen deprivation symptoms [ Time Frame: Up to 24 months post-surgery ]
  Will be measured by the FACT-ES. The FACT total score (calculated from the physical, functional, social and emotional well-being subscales) and ES subscale will be assessed. Higher scores indicate better QOL for the FACT-ES and better functioning for the FSFI total score.
• Sexual dysfunction [ Time Frame: Up to 24 months post-surgery ]
  Will be measured by the Female Sexual Function Index (FSFI). Higher scores indicate better functioning for the FSFI total score.
• Menopausal symptoms [ Time Frame: Up to 24 months post-surgery ]
  Will be measured by the Menopausal Symptom Checklist (MSCL).
• Cancer distress [ Time Frame: Up to 24 months post-surgery ]
  Will be measured by the Impact of Events Scale (IES).
• Medical decision making [ Time Frame: Up to 24 months post-surgery ]
  Will be measured by the Shared Decision Making Questionnaire (SDM-Q-9) to determin factors associated with the risk of reducing surgical treatment choice. The SDM-Q-9 total score at each time point of collection will be compared between arms using a t-test with a significance level of 0.05. A linear model will be used to assess the association of the SDM-Q-9 total score with treatment arm and patient characteristics such as age and race.
• Medical decision making [ Time Frame: Up to 24 months post-surgery ]
  Will be measured by the Decisional Regret Scale to determine factor associated with the risk of reducing surgical treatment choice. The Decisional Regret Scale total score at each time point of collection will be compared between arms using a t-test with a significance level of 0.05. A linear model will be used to assess the association of the Decisional Regret Scale total score with treatment arm and patient characteristics such as age, race, crossover from BLS arm, and hysterectomy status.
• Incidence of adverse events [ Time Frame: Up to 24 months post-surgery ]
  Will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. Counts and frequencies will be provided for the worst grade adverse event (AE) experienced by the patient by treatment arm. The distribution of AE grade in the BLS arm will be compared to the BSO arm using a chi-square test, or Fisher's exact test if cell frequencies are < 5, at the one-sided 0.05 significance level.

Current Other Pre-specified Outcome Measures (submitted: February 15, 2023)

• Cost effectiveness [ Time Frame: Up to 24 months post-surgery ]
  Will be measured by European Quality of Life Five Dimension Five Level Scale Questionnaire. A Markov model will be used to model cost.
• Section dysfunction (pre-menopausal patients only) [ Time Frame: Up to 24 months-post surgery ]
  Will be measured by selected Patient-Reported Outcomes Measurement Information System (PROMIS) screener and external sexual function items. Each item will be analyzed separately and compared between treatment arms using a chi-square test.
• Health related (HR)-QOL [ Time Frame: Up to 24 months post-surgery ]
  Will examine the correlation between HR-QOL, as measured by the FACT, with menopausal symptoms, as measured by the MCL, sexual dysfunction, as measured by FSFI, and PROMIS screener and external sexual function items and cancer distress as measured by the IES. Pearson correlation coefficients will be used for correlating the FACT total score with the FSFI overall score and Impact of Events Scale total distress score. Spearman correlation coefficients will be used to assess the correlation between FACT total score and the Menopausal Symptom Checklist symptoms, FSFI, and PROMIS items.
• Risk-reducing medical decision making validation and assessment [ Time Frame: Up to 24 months post-surgery ]
  Measured by population-specific items examining the factors associated with the risk reducing surgical treatment choice. Will by assessed using the Risk-Reducing Medical Decision Making survey.

Original Other Pre-specified Outcome Measures (submitted: January 30, 2020)

• Cost effectiveness [ Time Frame: Up to 24 months post-surgery ]
  Will be measured by European Quality of Life Five Dimension Five Level Scale Questionnaire (EQ-5D-5L). A Markov model will be used to model cost.
• Sexual dysfunction by PROMIS screener [ Time Frame: Up to 20 years ]
  Will be measured by selected Patient-Reported Outcomes Measurement Information System (PROMIS) screener. Each item will be analyzed separately and compared between treatment arms using a chi-square test.
• Section dysfunction by PROMIS external sexual function items [ Time Frame: Up to 20 years ]
  Will be measured by selected PROMIS external sexual function items. Each item will be analyzed separately and compared between treatment arms using a chi-square test.
• Correlation between Health related (HR)-QOL and patient reported symptoms. [ Time Frame: Up to 24 months post-surgery ]
  Will examine the correlation between HR-QOL, as measured by the FACT, with menopausal symptoms, as measured by the MCL, sexual dysfunction, as measured by FSFI, and PROMIS screener and external sexual function items and cancer distress as measured by the IES. Pearson correlation coefficients will be used for correlating the FACT total score with the FSFI overall score and IES total distress score. Spearman correlation coefficients will be used to assess the correlation between FACT total score and the MSCL symptoms, FSFI, and PROMIS items.

Descriptive Information

• Brief Title: A Study to Compare Two Surgical Procedures in Individuals With BRCA1 Mutations to Assess Reduced Risk of Ovarian Cancer
• Official Title: A Non-Randomized Prospective Clinical Trial Comparing the Non-Inferiority of Salpingectomy to Salpingo-Oophorectomy to Reduce the Risk of Ovarian Cancer Among BRCA1 Carriers [SOROCk]
• Brief Summary: This clinical trial studies how well two surgical procedures (bilateral salpingectomy and bilateral salpingo-oophorectomy) work in reducing the risk of ovarian cancer for individuals with BRCA1 mutations. Bilateral salpingectomy involves the surgical removal of fallopian tubes, and bilateral salpingo-oophorectomy involves the surgical removal of both the fallopian tubes and ovaries. This study may help doctors determine if the two surgical procedures are nearly the same for ovarian cancer risk reduction for women with BRCA1 mutations.

Detailed Description

PRIMARY OBJECTIVE:

I. To compare the non-inferiority of bilateral salpingectomy (BLS) with delayed oophorectomy to bilateral salpingo-oophorectomy (BSO) to reduce the risk of ovarian cancer among individuals with deleterious BRCA1 germline mutations.

SECONDARY OBJECTIVES:

I. To prospectively assess estrogen deprivation symptoms in pre-menopausal BLS patients as measured by the Functional Assessment of Cancer Therapy - Endocrine Symptom (FACT-ES) subscale compared to pre-menopausal patients in the BSO arm.

II. To determine if health-related quality of life (QOL) (FACT) is negatively impacted by menopausal symptoms (menopausal symptom checklist-Menopausal Symptom Checklist [MSCL]) and sexual dysfunction (Female Sexual Function Index [FSFI]) in pre-menopausal patients who have undergone BLS, in comparison to normative data (MSCL/FACT-ES) and data from pre-menopausal BSO patients.

III. To determine if health-related QOL (FACT) is negatively impacted by cancer distress (Impact of Event Scale [IES]) in individuals who have undergone BLS, in comparison to BSO patients.

IV. To assess medical decision making, as measured by the Shared Decision Making Questionnaire (SDM-Q-9) and Decision Regret Scale (DRS), and determine factors associated with the risk of reducing surgical treatment choice.

V. To assess adverse events, graded using Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.

EXPLORATORY OBJECTIVES:

I. Sexual dysfunction, as measured by selected Patient-Reported Outcomes Measurement Information System (PROMIS) screener and external sexual function items (pre-menopausal patients).

II. To estimate the cost-effectiveness of BLS compared to BSO for ovarian cancer risk reduction.

III. To assess medical decision making, as measured by the Risk-Reducing Medical Decision Making (RR-MDM) survey, a targeted set of questions on risk reducing surgical treatment choice.

TRANSLATIONAL RESEARCH OBJECTIVE:

I. To bank tissue and blood biospecimens for future research.

OUTLINE: Patients are assigned to 1 of 2 groups.

GROUP I: Patients undergo bilateral salpingectomy. Patients may then undergo oophorectomy after initial surgery.

GROUP II: Patients undergo bilateral salpingo-oophorectomy.

Patients in both groups also undergo a transvaginal ultrasound during screening and blood sample collection throughout the trial.

After completion of study, patients are followed up at 10-60 days, 6, 12, and 24 months, and then annually for up to 20 years.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Non-Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Ovarian Carcinoma

Intervention

• Procedure: Bilateral Salpingectomy
  Undergo bilateral salpingectomy
• Procedure: Bilateral Salpingectomy with Oophorectomy
  Undergo bilateral salpingo-oophorectomy
  Other Name: bilateral salpingo-oophorectomy
• Procedure: Biospecimen Collection
  Undergo blood sample collection
  Other Names:

  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
• Other: Quality-of-Life Assessment
  Ancillary studies
  Other Name: Quality of Life Assessment
• Other: Questionnaire Administration
  Ancillary studies
• Procedure: Transvaginal Ultrasound
  Undergo transvaginal ultrasound
  Other Names:

  • transvaginal sonography
  • TVS
  • TVU

Study Arms

• Experimental: Group I (bilateral salpingectomy)
  Patients undergo bilateral salpingectomy. Patients may then undergo oophorectomy after initial surgery. Patients also undergo a transvaginal ultrasound during screening and blood sample collection throughout the trial.
  Interventions:

  • Procedure: Bilateral Salpingectomy
  • Procedure: Biospecimen Collection
  • Other: Quality-of-Life Assessment
  • Other: Questionnaire Administration
  • Procedure: Transvaginal Ultrasound
• Active Comparator: Group II (bilateral salpingo-oophorectomy)
  Patients undergo bilateral salpingo-oophorectomy. Patients also undergo a transvaginal ultrasound during screening and blood sample collection throughout the trial.
  Interventions:

  • Procedure: Bilateral Salpingectomy with Oophorectomy
  • Procedure: Biospecimen Collection
  • Other: Quality-of-Life Assessment
  • Other: Questionnaire Administration
  • Procedure: Transvaginal Ultrasound

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 30, 2020): 2262
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 23, 2037
• Estimated Primary Completion Date: June 23, 2036 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Individuals 35-50 years of age, inclusive
• Patients who are undergoing risk-reducing salpingo-oophorectomy (RRSO) (for the BSO arm) and patients who have declined or elected to defer BSO after proper counselling to clearly explain the standard of care for BRCA1 mutation carriers and are undergoing salpingectomy (for the BLS arm with delayed oophorectomy arm). Concurrently planned hysterectomy with either arm is permitted
• At least one intact ovary and fallopian tube is in situ at the time of counseling and consent. Prior hysterectomy is allowed provided it did not include bilateral salpingectomy. Prior tubal ligation is allowed if one intact ovary and fallopian tube (with fimbria not removed) are present
• Positive Clinical Laboratory Improvement Act (CLIA)-approved test results for pathogenic or likely pathogenic germline BRCA1 mutation in the patient. Documentation of the result is required
• Patients may be premenopausal or menopausal
• Transvaginal ultrasound (TVUS) and CA-125 within 180 days of registration
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
• Individuals who are currently pregnant or plan to become pregnant in the future through assisted reproductive technologies and who have received proper counseling are eligible. Individuals who are currently pregnant and plan bilateral salpingectomy at the time of a planned cesarean section are eligible. Patients must understand that they will not be able to become pregnant naturally in the future

Exclusion Criteria:

• Individuals with a history of any prior cancer who have received chemotherapy within the past 30 days or radiotherapy to abdomen or pelvis at any prior time
• Prior history of ovarian cancer, including low malignant potential neoplasms (LMP), primary peritoneal carcinoma, or fallopian tube carcinoma
• Patients medically unfit for the planned surgical procedure

• Patients with abnormal screening tests (TVUS, CA-125) suspicious for occult or gross pelvic malignancy or neoplasm within the past 180 days

  • An abnormal TVUS is defined as morphologic or structural variations suspicious for ovarian malignancy or complex cystic lesions (simple cysts < 5 cm in maximal diameter are not exclusionary)
  • An abnormal CA-125 is defined as a level > 50 U/ml in premenopausal individuals if they are not current users of oral contraceptives; an abnormal CA-125 is defined as a level > 40 U/ml for premenopausal individuals who are current users of oral contraceptives. An abnormal CA-125 is defined as a level > 35 U/ml in postmenopausal individuals.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 35 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: No
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04251052
• Other Study ID Numbers: NRG-CC008; NCI-2019-07791 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); NRG-CC008 ( Other Identifier: NRG Oncology ); NRG-CC008 ( Other Identifier: DCP ); NRG-CC008 ( Other Identifier: CTEP ); UG1CA189867 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: NRG Oncology
• Original Responsible Party: Same as current
• Current Study Sponsor: NRG Oncology
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Kathryn P Pennington; NRG Oncology

• PRS Account: NRG Oncology
• Verification Date: February 2023