NCT03382574

Pilot Study of Denosumab in BRCA1/2 Mutation Carriers Scheduled for Risk-Reducing Salpingo-Oophorectomy

• Status: Terminated
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This randomized pilot early phase I trial studies how well denosumab works in BRCA1/2 mutations carriers scheduled for risk-reducing salpingo-oophorectomy. Denosumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread.

Detailed description

PRIMARY OBJECTIVE: I. To compare the effect of denosumab 120 mg subcutaneously every 4 weeks for 1-2 doses to no treatment in the pre-surgical setting on Ki67 proliferation index by immunohistochemistry (IHC) in the fimbrial end of the fallopian tube of premenopausal BRCA1/2 mutation carriers undergoing risk-reducing salpingo-oophorectomy, with or without hysterectomy. SECONDARY OBJECTIVES: I. To assess Ki67 proliferation index by immunohistochemistry (IHC) in ovarian surface epithelium and endometrium (if also undergoing a hysterectomy, \~20% of participants) after exposure to denosumab compared to no treatment. II. To investigate other tissue-based biomarkers in the fimbrial end of the fallopian tube, ovarian surface epithelium, and endometrium (if also undergoing hysterectomy) after exposure to denosumab compared to no treatment, including: IIa. Apoptosis with cleaved caspase-3 by IHC. IIb. Receptor activator of NF-KB (RANK) and RANK ligand (RANKL) expression by IHC. IIc. Estrogen receptor (ER) and progesterone receptor (PR) expression by IHC. IId. CD44 and p53 expression by IHC. IIe. Signal transducer and activator of transcription 3 (STAT3) and phosphorylated-STAT3 (pSTAT3) expression by IHC. III. To analyze gene expression profiling in the fimbrial end of the fallopian tube and ovarian surface epithelium after exposure to denosumab compared to no treatment. IV. To investigate serum biomarkers at baseline (pre-treatment) and time of surgery (post-treatment) with denosumab compared to no treatment, including: IVa. Progesterone. IVb. Estradiol. IVc. Denosumab drug levels. V. To investigate serial serum C-terminal telopeptide (CTX) levels from baseline (pre-treatment) to time of surgery to 9 months and 12 months after start of intervention with denosumab compared to no treatment. VI. To monitor safety and adverse effects of denosumab compared to no treatment. OUTLINE: Patients are randomized 1 of 2 arms. ARM I: Beginning within 3 days of menstrual cycle, patients receive denosumab subcutaneously (SC) every 4 weeks for 1-2 doses and undergo risk-reducing salpingo-oophorectomy 14-28 days after last dose. ARM II: Patients receive no treatment for 2-8 weeks and then undergo risk-reducing salpingo-oophorectomy. After completion of study treatment, patients are followed up at 6, 9, and 12 months.

Conditions

• Ovarian Carcinoma

Interventions

Type	Name	Description
BIOLOGICAL	Denosumab	Given SC
PROCEDURE	Salpingo-Oophorectomy	Undergo risk-reducing salpingo-oophorectomy

Timeline

• Start date: 2019-03-14
• Primary completion: 2021-10-22
• Completion: 2021-10-22
• First posted: 2017-12-26
• Last updated: 2022-06-14
• Results posted: 2022-06-14

Locations

6 sites across 2 countries: United States, Israel

Regulatory

• FDA-regulated drug study