Trial Outcomes & Findings for Pilot Study of Denosumab in BRCA1/2 Mutation Carriers Scheduled for Risk-Reducing Salpingo-Oophorectomy (NCT NCT03382574)
NCT ID: NCT03382574
Last Updated: 2022-06-14
Results Overview
Will be assessed using immunohistochemistry (IHC). Quantitative measures of the expression of Ki67 based upon percentage of positive cells will be scored by a pathologist blinded to treatment assignment. In order to evaluate the difference of Ki67 expression between the two arms, 2-sample t-test will be considered.
TERMINATED
EARLY_PHASE1
2 participants
Up to 12 months
2022-06-14
Participant Flow
This multicenter protocol will be conducted at the following five sites: Columbia University Irving Medical Center (CUIMC), New York, NY; Weill-Cornell Medical Center, New York, NY; the Dana Farber Cancer Institute (DFCI), Boston, MA; and Tel Aviv Sourasky Medical Center and Chaim Sheba Medical Center, Tel Aviv, Israel.
2 participants consented at Tel Aviv Sourasky Medical Center, no participants randomized nor received trial intervention (Participant 1 was deemed ineligible due to elevated FSH level and Participant 2 did not start intervention due to COVID-19 lockdown restrictions).
Participant milestones
| Measure |
Arm I (Denosumab, Risk-reducing Salpingo-oophorectomy)/Arm II (Risk-reducing Salpingo-oophorectomy)
Beginning within 3 days of menstrual cycle, patients receive denosumab SC every 4 weeks for 1-2 doses and undergo risk-reducing salpingo-oophorectomy 14-28 days after last dose.
Denosumab: Given SC
Salpingo-Oophorectomy: Undergo risk-reducing salpingo-oophorectomy
Arm II Patients receive no treatment for 2-8 weeks and then undergo risk-reducing salpingo-oophorectomy.
Salpingo-Oophorectomy: Undergo risk-reducing salpingo-oophorectomy
|
|---|---|
|
Overall Study
STARTED
|
0
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pilot Study of Denosumab in BRCA1/2 Mutation Carriers Scheduled for Risk-Reducing Salpingo-Oophorectomy
Baseline characteristics by cohort
Baseline data not reported
PRIMARY outcome
Timeframe: Up to 12 monthsPopulation: No participants were randomized, therefore no data collected.
Will be assessed using immunohistochemistry (IHC). Quantitative measures of the expression of Ki67 based upon percentage of positive cells will be scored by a pathologist blinded to treatment assignment. In order to evaluate the difference of Ki67 expression between the two arms, 2-sample t-test will be considered.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 12 monthsPopulation: No participants were randomized, therefore no data collected.
Will be assessed using IHC. In order to evaluate the difference of Ki67 expression between the two arms, 2-sample t-test will be considered.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 12 monthsPopulation: No participants were randomized, therefore no data collected.
Will be assessed using IHC. Including: apoptosis with cleaved caspase-3 (IHC), RANK/RANKL (IHC), estrogen receptor (ER)/progesterone receptor (PR) (IHC), CD44 and p53 (IHC), and STAT3 and pSTAT3 (IHC). Values of tissue-based biomarkers measurements such as tissue Ki67 proliferation index, serum progesterone, etc., which are continuous variables, will be summarized by descriptive statistics including mean, standard deviation, median and range. For tissue biomarkers, linear regression models will be employed to investigate the association of treatment while adjusting for possible confounders (i.e., age, race, etc.). Normality, homoscedasticity, independence of errors, and lack of multicollinearity in the covariates will be evaluated; if needed, proper transformation will be considered.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 12 monthsPopulation: No participants were randomized, therefore no data collected.
For gene expression profiling analysis, nSolver Analysis Software (nanoString Technologies, Washington \[WA\]) will be used. Geometric mean is used for calculation of normalization factors. Student's t test is used to calculate differential expression.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to time of surgeryPopulation: No participants were randomized, therefore no data collected.
Values of serum biomarkers measurements such as tissue Ki67 proliferation index, serum progesterone, etc., which are continuous variables, will be summarized by descriptive statistics including mean, standard deviation, median and range.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline up to 12 months after start of interventionPopulation: No participants were randomized, therefore no data collected.
2-sample t-test may be applied to evaluate any change in serum biomarkers from baseline to after intervention. To investigate the overall changes in serum biomarkers, a linear mixed model that accommodates intra-participant correlation due to repeated measurements will be utilized adjusting for any potential covariates.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 12 months after start of treatmentPopulation: No participants were randomized, therefore no data collected.
Categorical variables, such as adverse events, will be summarized by frequency and proportion.
Outcome measures
Outcome data not reported
Adverse Events
Arm I (Denosumab, Risk-reducing Salpingo-oophorectomy)
Arm II (Risk-reducing Salpingo-oophorectomy)
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Dr. Powel Brown, Chair, Clinical Cancer Prevention
UT MD Anderson Cancer Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place