Vitamin D for Women at Increased Risk of Developing Ovarian, Fallopian, or Primary Peritoneal Cancer

Not Applicable

Terminated

Brief Summary: The purpose of this research is to study Vitamin D3 replacement for patients at high risk of developing ovarian, fallopian tube, or peritoneal cancer, and see if the Vitamin D3 replacement may be able to prevent the cancer.

This study is being done because in the United States ovarian cancer is the leading cause of death among women with gynecologic cancer. Women with BRCA mutations, a personal history of breast cancer, and a family history of breast and ovarian cancer are at high risk of developing ovarian, fallopian, and primary peritoneal cancer. Novel treatments other than surgery which can decrease the risk of developing ovarian, fallopian tube, and primary peritoneal cancer are important. Vitamin D has been shown to reduce the risk of developing bladder, breast, colon, endometrial, esophageal, gallbladder, gastric, lung, pancreatic, prostate, rectal, renal, vulvar and Hodgkin and non-Hodgkin lymphoma, and it may play a role in the prevention of ovarian cancer.

Recruitment & Eligibility

Inclusion Criteria

Patients must be undergoing prophylactic or therapeutic oophorectomy
Patients must be considered to be at a high risk of developing ovarian, fallopian or primary peritoneal cancer, according to 1 or more of the following characteristics:
Patients with a BRCA mutation including variants of uncertain significance
Patients with Lynch syndrome
Patients with a family history that places them at high risk of developing ovarian cancer
Patients with a personal history of breast cancer
Patients currently taking Vitamin D prior to registration will be eligible if serum Vitamin D levels are <60ng/ml. We believe that most of these patients will be on low replacement doses of Vitamin D3 to begin with but in order to prevent against toxicity their Vitamin D3 levels will be checked at the start of the trial.
Patients must be women age 18 and older
Patients who are of childbearing potential and sexually active must use contraception while on study.
Patients must have a signed and witnessed informed consent and authorization permitting release of personal health information prior to registration on the study.

Exclusion Criteria

Patients who are unable to take Vitamin D3 supplementation are NOT eligible
Patients who are unwilling or unable to undergo oophorectomy are NOT eligible
Patients with suspicious or abnormal findings on preoperative physical exam, laboratory results, or imaging studies within 4 weeks of treatment start are NOT eligible
Patients with a GFR <59 within 4 weeks of treatment start are NOT eligible
Patients are NOT eligible if they exhibit any contraindications within 4 weeks of treatment start to 25 (OH) D supplement including:
Hypercalcemia (>11.5mg/dL)
Hypervitaminosis D
Malabsorption syndrome
Active gallbladder disease
Active hepatic disease
Hypoparathyroidism
Leukemia
Nephrolithiasis
Renal failure sarcoidosis
Renal disease (eGFR<59 ml/min/1.73m2)
Patients currently receiving digoxin are NOT eligible
Patients who are pregnant or breastfeeding are NOT eligible. Patients must have a negative urine pregnancy test at baseline (within 4 weeks of treatment start) to confirm eligibility

Arm && Interventions

Group	Intervention	Description
Arm B: Placebo Group	Placebo	Patients will take a placebo by mouth prior to and including the morning of surgery. If bloods tests done at the start of study show that the patients have a low (\< or = 30 ng/ml) Vitamin D level, patients will be given 2 placebo tablets to take once a week until surgery. If baseline Vitamin D level is \> 30 ng/ml, patients will be given on placebo tablet to take once a day until surgery.

Primary Outcome Measures

Name	Time	Method
The Outcomes That Will be Measured for the Primary Objectives of This Study Will be Surrogate Endpoint Biomarkers Markers of Cancer Prevention	Up to 24 months	Activation of apoptosis via immunohistochemical measurement of activation of caspase activity, as well as expression of BAX and BCL-2 The primary marker outcomes will be assessed for normality and compared between groups using a two-sample t-test or a Wilcoxon rank sum test. Other markers will be compared similarly if continuous, or by Fisher's exact test if categorical.
Other Surrogate Endpoint Biomarkers Markers of Cancer Prevention	Up to 24 months	Decrease in cellular proliferation measured by immunohistochemistry staining with KI67

Secondary Outcome Measures

Name	Time	Method
Review of Standard Pathologic Evaluation With Specific Attention to Histologic Markers	Up to 24 months	The outcomes that will be measured for the secondary objectives of this study will include the following: Review of standard pathologic evaluation with specific attention to histologic markers including serous hyperplasia, tubal atypia, and p53 signature in the ovary and fallopian tube, and examine via immunohistochemistry the effects of vitamin D supplementation on expression of the TGF-beta isoforms and CYP24
Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement.	Up to 24 months	Differences in the types and incidence of toxicities associated with Vitamin D3 replacement, specifically hypercalcemia, with increasing levels of Vitamin D3 along with the effectiveness of Vitamin D3 supplementation on increasing serum levels of Vitamin D

Locations (2): Northwestern University
🇺🇸
Chicago, Illinois, United States
NorthShore University HealthSystem
🇺🇸
Evanston, Illinois, United States