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

Purpose

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.

Condition	Intervention
Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Cancer	Dietary Supplement: Arm A: Vitamin D3 Group Dietary Supplement: Placebo

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Prevention
Official Title:	A Randomized Controlled Pilot Trial of Vitamin D3 Replacement of Placebo Followed by Bilateral Salpingo-Oophorectomy for Women at Increased Risk of Developing Ovarian, Fallopian, or Primary Peritoneal Cancer.

Resource links provided by NLM:

MedlinePlus related topics: Cancer Ovarian Cancer Vitamin D

Drug Information available for: Cholecalciferol Vitamin D

U.S. FDA Resources

Further study details as provided by Northwestern University:

Primary Outcome Measures:

The outcomes that will be measured for the primary objectives of this study will be surrogate endpoint biomarkers markers of cancer prevention [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
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 [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
Decrease in cellular proliferation measured by immunohistochemistry staining with KI67

Secondary Outcome Measures:

Review of standard pathologic evaluation with specific attention to histologic markers [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
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. [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
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

Estimated Enrollment:	80
Study Start Date:	October 2012
Estimated Study Completion Date:	October 2016
Estimated Primary Completion Date:	October 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Arm A: Vitamin D3 Group Patients will take Vitamin D3 by mouth in the weeks prior to and including the morning of surgery. If blood test done at the start of the study shows that patients have a low (< or = 30 ng/ml) Vitamin D level, patients will be given two 25,000 IU Vitamin D3 Tablets (for a total of 50,000 IU) to take once a week until surgery. If baseline Vitamin D level is >30ng/ml, patients will be given on 2,000 IU Vitamin D3 tablet to take once a day until day of surgery.	Dietary Supplement: Arm A: Vitamin D3 Group
Placebo Comparator: Arm B: Placebo Group 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.	Dietary Supplement: Placebo

Arms

Assigned Interventions

Active Comparator: Arm A: Vitamin D3 Group

Patients will take Vitamin D3 by mouth in the weeks prior to and including the morning of surgery. If blood test done at the start of the study shows that patients have a low (< or = 30 ng/ml) Vitamin D level, patients will be given two 25,000 IU Vitamin D3 Tablets (for a total of 50,000 IU) to take once a week until surgery. If baseline Vitamin D level is >30ng/ml, patients will be given on 2,000 IU Vitamin D3 tablet to take once a day until day of surgery.

Dietary Supplement: Arm A: Vitamin D3 Group

Placebo Comparator: Arm B: Placebo Group

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.

Dietary Supplement: Placebo

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01744821

Contacts

Contact: Nikki Neubauer, MD	(312) 472-4684	nneubauer@nmff.org
Contact: Cary Passaglia, BS	(312) 472-5725	c-passaglia@northwestern.edu

Locations

United States, Illinois
Northwestern University	Recruiting
Chicago, Illinois, United States, 60611
Contact: Nikki Neubauer, MD 312-695-0990 nneubauer@nmff.org
Contact: Cary Passaglia, BS (312) 472-5725 c-passaglia@northwestern.edu
Principal Investigator: Julian Schink, MD

Sponsors and Collaborators

Northwestern University

More Information

No publications provided

Responsible Party:	Nikki Neubauer, Principal Investigator, Northwestern University
ClinicalTrials.gov Identifier:	NCT01744821 History of Changes
Other Study ID Numbers:	STU00064898
Study First Received:	November 30, 2012
Last Updated:	April 8, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by Northwestern University:

High Risk

Additional relevant MeSH terms:

Ovarian Neoplasms
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Abdominal Neoplasms

Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Fallopian Tube Diseases
Cholecalciferol
Vitamin D
Ergocalciferols
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on May 23, 2013