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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04251052
Recruitment Status : Recruiting
First Posted : January 31, 2020
Last Update Posted : November 24, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
NRG Oncology

Tracking Information
First Submitted Date  ICMJE January 14, 2020
First Posted Date  ICMJE January 31, 2020
Last Update Posted Date November 24, 2021
Actual Study Start Date  ICMJE June 23, 2020
Estimated Primary Completion Date June 23, 2036   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 12, 2021)
  • 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.
  • Sexual dysfunction [ 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 [ 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.
  • Cancer distress [ Time Frame: Up to 24 months post-surgery ]
    Will be measured by the Impact of Events Scale (IES).
  • 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. Models will also include hormonal therapy as a covariate.
  • 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 (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 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.
Original Secondary Outcome Measures  ICMJE
 (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: September 11, 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.
  • Section dysfunction [ 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 (RR-MDM) 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  ICMJE A Study to Compare Two Surgical Procedures in Women With BRCA1 Mutations to Assess Reduced Risk of Ovarian Cancer
Official Title  ICMJE 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 trial studies how well two surgical procedures (bilateral salpingectomy and bilateral salpingo-oophorectomy) work in reducing the risk of ovarian cancer for women 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 women with deleterious BRCA1 germline mutations.

SECONDARY OBJECTIVES:

I. To prospectively assess estrogen deprivation symptoms in BLS patients as measured by the Functional Assessment of Cancer Therapy - Endocrine Symptom (FACT-ES) subscale compared to women 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]), sexual dysfunction (Female Sexual Function Index [FSFI]), and cancer distress (Impact of Events Scale [IES]) in women who have undergone BLS, in comparison to normative data (MSCL/FACT-ES) and data from BSO patients.

III. 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.

IV. 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.

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

III. To determine the association between health related (HR)-QOL with menopausal symptoms, as measured by the MSCL, sexual dysfunction, as measured by FSFI/PROMIS screener and external sexual function items, and cancer distress as measured by the IES.

IV. 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 (pending funding).

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.

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  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Ovarian Carcinoma
Intervention  ICMJE
  • Procedure: Bilateral Salpingectomy
    Undergo bilateral salpingectomy
  • Procedure: Bilateral Salpingectomy with Oophorectomy
    Undergo bilateral salpingo-oophorectomy
    Other Name: bilateral salpingo-oophorectomy
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Name: Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies
Study Arms  ICMJE
  • Experimental: Group I (bilateral salpingectomy)
    Patients undergo bilateral salpingectomy. Patients may then undergo oophorectomy after initial surgery.
    Interventions:
    • Procedure: Bilateral Salpingectomy
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
  • Active Comparator: Group II (bilateral salpingo-oophorectomy)
    Patients undergo bilateral salpingo-oophorectomy.
    Interventions:
    • Procedure: Bilateral Salpingectomy with Oophorectomy
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 30, 2020)
2262
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 23, 2037
Estimated Primary Completion Date June 23, 2036   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Women 35-50 years of age, inclusive
  • Patients who have declined or elected to defer risk-reducing salpingo-oophorectomy (RRSO) after proper counselling to clearly explain the standard of care for BRCA1 mutation carriers (for the BLS with delayed oophorectomy arms) or patients who are undergoing RRSO (for the RRSO arm)
  • 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 tube are present
  • Positive Clinical Laboratory Improvement Act (CLIA)-approved test results for pathogenic or likely pathogenic germline BRCA1 mutation in the patient herself. Documentation of the result is required
  • Premenopausal; defined as < 12 months of amenorrhea. However, for those patients with >= 12 months of amenorrhea who may be pre-menopausal or patients with a prior hysterectomy with at least one retained ovary/tube, levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and in the premenopausal range per local institutional standards will be acceptable. Concurrently planned hysterectomy with salpingectomy for the BS group or with BSO for the BSO group is permitted
  • 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

Exclusion Criteria:

  • Women with a history of any prior cancer who have received chemotherapy within the past 12 months, hormonal therapy in the past 90 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 this study population of premenopausal women if they are not current users of oral contraceptives; an abnormal CA-125 is defined as a level > 40 U/ml for premenopausal women who are current users of oral contraceptives
  • Women who are currently pregnant or plan to become pregnant in the future
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 35 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04251052
Other Study ID Numbers  ICMJE 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  ICMJE Not Provided
Responsible Party NRG Oncology
Study Sponsor  ICMJE NRG Oncology
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Joan Walker NRG Oncology
PRS Account NRG Oncology
Verification Date November 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP