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

• Sponsor: Northwestern University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01744821
• Collaborator: (none)
• Enrollment: 7
• Locations: 2
• Arms: 2
• Duration (Months): 30
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer	Dietary Supplement: Arm A: Vitamin D3 Group; Dietary Supplement: Placebo	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, 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.
• Study Start Date: Oct 1, 2012
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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

1. 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

2. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University	Chicago	Illinois	United States	60611
2	NorthShore University HealthSystem	Evanston	Illinois	United States	60201

Sponsors and Collaborators

• Northwestern University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Northwestern University
• ClinicalTrials.gov Identifier: NCT01744821
• Other Study ID Numbers: STU00064898
• First Posted: Dec 7, 2012
• Last Update Posted: Jul 23, 2015
• Last Verified: Jul 1, 2015

• Keywords provided by Northwestern University: High Risk
• Additional relevant MeSH terms: Fallopian Tube Neoplasms; Peritoneal Neoplasms; Vitamin D; Cholecalciferol

Study Results

Participant Flow

Recruitment Details	Eligible participants were women at high risk for ovarian cancer and undergoing a prophylactic salpingo-oophorectomy. Subjects were recruited in the outpatient gynecologic oncology clinics of the study investigators. The study opened 6/1/12 with a goal of 80 subjects. It closed on 1/12/15 with a total of 7 subjects.
Pre-assignment Detail	Baseline evaluation included physical examination, personal and family history questionnaire, and blood test including serum 25(OH)D. Based on vitamin D level, subjects were randomized to 1 of 4 groups.

Arm/Group Title	Vitamin D 50,000 IU Weekly	Placebo 50,000 IU Weekly	Vitamin D 2,000 IU Daily	Placebo 2,000 IU Daily
Arm/Group Description	If Vitamin D level is ≤ 30ng/ml at baseline, randomized to 50,000 IU p.o. weekly until surgery (levels will be rechecked every 4 weeks)	If Vitamin D level is ≤ 30ng/ml at baseline, randomized to Placebo p.o. weekly until surgery (levels will be rechecked every 4 weeks)	If Vitamin D level is>30ng/ml at baseline, randomized to 2000 IU p.o. daily until surgery (levels will be rechecked every 4 week)	If Vitamin D level is>30ng/ml at baseline, randomized to Placebo p.o. daily until surgery (levels will be rechecked every 4 weeks)
Period Title: Overall Study
STARTED	1	3	2	1
COMPLETED	1	3	2	1
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Vitamin D 50,000 IU Weekly	Placebo 50,000 IU Weekly	Vitamin D 2,000 IU Daily	Placebo 2,000 IU Daily	Total
Arm/Group Description	If Vitamin D level is ≤ 30ng/ml at baseline, randomized to 50,000 IU p.o. weekly until surgery (levels will be rechecked every 4 weeks)	If Vitamin D level is ≤ 30ng/ml at baseline, randomized to Placebo p.o. weekly until surgery (levels will be rechecked every 4 weeks)	If Vitamin D level is>30ng/ml at baseline, randomized to 2000 IU p.o. daily until surgery (levels will be rechecked every 4 week)	If Vitamin D level is>30ng/ml at baseline, randomized to Placebo p.o. daily until surgery (levels will be rechecked every 4 weeks)	Total of all reporting groups
Overall Participants	1	3	2	1	7
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	1 100%	3 100%	2 100%	1 100%	7 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	1 100%	3 100%	2 100%	1 100%	7 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%	3 100%	2 100%	1 100%	7 100%

Outcome Measures

1. Primary Outcome

Title	The Outcomes That Will be Measured for the Primary Objectives of This Study Will be Surrogate Endpoint Biomarkers Markers of Cancer Prevention
Description	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.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

We failed to accrue enough patients in order to conduct this outcome measure. We collected the specimens but were unable to analyze them given the low accrual numbers.

Arm/Group Title	Vitamin D 50,000 IU Weekly	Placebo 50,000 IU Weekly	Vitamin D 2,000 IU Daily	Placebo 2,000 IU Daily
Arm/Group Description	If Vitamin D level is ≤ 30ng/ml at baseline, randomized to 50,000 IU p.o. weekly until surgery (levels will be rechecked every 4 weeks)	If Vitamin D level is ≤ 30ng/ml at baseline, randomized to Placebo p.o. weekly until surgery (levels will be rechecked every 4 weeks)	If Vitamin D level is>30ng/ml at baseline, randomized to 2000 IU p.o. daily until surgery (levels will be rechecked every 4 week)	If Vitamin D level is>30ng/ml at baseline, randomized to Placebo p.o. daily until surgery (levels will be rechecked every 4 weeks)
Measure Participants	0	0	0	0

2. Primary Outcome

Title	Other Surrogate Endpoint Biomarkers Markers of Cancer Prevention
Description	Decrease in cellular proliferation measured by immunohistochemistry staining with KI67
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

We failed to accrue enough patients in order to conduct this outcome measure. We collected the specimens but were unable to analyze them given the low accrual numbers.

Arm/Group Title	Vitamin D 50,000 IU Weekly	Placebo 50,000 IU Weekly	Vitamin D 2,000 IU Daily	Placebo 2,000 IU Daily
Arm/Group Description	If Vitamin D level is ≤ 30ng/ml at baseline, randomized to 50,000 IU p.o. weekly until surgery (levels will be rechecked every 4 weeks)	If Vitamin D level is ≤ 30ng/ml at baseline, randomized to Placebo p.o. weekly until surgery (levels will be rechecked every 4 weeks)	If Vitamin D level is>30ng/ml at baseline, randomized to 2000 IU p.o. daily until surgery (levels will be rechecked every 4 week)	If Vitamin D level is>30ng/ml at baseline, randomized to Placebo p.o. daily until surgery (levels will be rechecked every 4 weeks)
Measure Participants	0	0	0	0

3. Secondary Outcome

Title	Review of Standard Pathologic Evaluation With Specific Attention to Histologic Markers
Description	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
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

We failed to accrue enough patients in order to conduct this outcome measure. We collected the specimens but were unable to analyze them given the low accrual numbers.

Arm/Group Title	Vitamin D 50,000 IU Weekly	Placebo 50,000 IU Weekly	Vitamin D 2,000 IU Daily	Placebo 2,000 IU Daily
Arm/Group Description	If Vitamin D level is ≤ 30ng/ml at baseline, randomized to 50,000 IU p.o. weekly until surgery (levels will be rechecked every 4 weeks)	If Vitamin D level is ≤ 30ng/ml at baseline, randomized to Placebo p.o. weekly until surgery (levels will be rechecked every 4 weeks)	If Vitamin D level is>30ng/ml at baseline, randomized to 2000 IU p.o. daily until surgery (levels will be rechecked every 4 week)	If Vitamin D level is>30ng/ml at baseline, randomized to Placebo p.o. daily until surgery (levels will be rechecked every 4 weeks)
Measure Participants	0	0	0	0

4. Secondary Outcome

Title	Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement.
Description	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
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin D 50,000 IU Weekly	Placebo 50,000 IU Weekly	Vitamin D 2,000 IU Daily	Placebo 2,000 IU Daily
Arm/Group Description	If Vitamin D level is ≤ 30ng/ml at baseline, randomized to 50,000 IU p.o. weekly until surgery (levels will be rechecked every 4 weeks)	If Vitamin D level is ≤ 30ng/ml at baseline, randomized to Placebo p.o. weekly until surgery (levels will be rechecked every 4 weeks)	If Vitamin D level is>30ng/ml at baseline, randomized to 2000 IU p.o. daily until surgery (levels will be rechecked every 4 week)	If Vitamin D level is>30ng/ml at baseline, randomized to Placebo p.o. daily until surgery (levels will be rechecked every 4 weeks)
Measure Participants	1	3	2	1
Fatige grade 1	1 100%	0 0%	0 0%	0 0%
Headache grade 1	0 0%	1 33.3%	1 50%	0 0%
Hypercalcemia	0 0%	0 0%	0 0%	0 0%
Loss of Appetite grade 1	0 0%	1 33.3%	0 0%	0 0%
Dry Mouth grade 1	1 100%	1 33.3%	0 0%	0 0%
Constipation grade 1	1 100%	0 0%	0 0%	0 0%
Weakness grade 1	1 100%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	8 weeks
Arm/Group Title	Vitamin D 50,000 IU Weekly		Placebo 50,000 IU Weekly		Vitamin D 2,000 IU Daily		Placebo 2,000 IU Daily
Arm/Group Description	If Vitamin D level is ≤ 30ng/ml at baseline, randomized to 50,000 IU p.o. weekly until surgery (levels will be rechecked every 4 weeks)		If Vitamin D level is ≤ 30ng/ml at baseline, randomized to Placebo p.o. weekly until surgery (levels will be rechecked every 4 weeks)		If Vitamin D level is>30ng/ml at baseline, randomized to 2000 IU p.o. daily until surgery (levels will be rechecked every 4 week)		If Vitamin D level is>30ng/ml at baseline, randomized to Placebo p.o. daily until surgery (levels will be rechecked every 4 weeks)
All Cause Mortality
	Vitamin D 50,000 IU Weekly		Placebo 50,000 IU Weekly		Vitamin D 2,000 IU Daily		Placebo 2,000 IU Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Vitamin D 50,000 IU Weekly		Placebo 50,000 IU Weekly		Vitamin D 2,000 IU Daily		Placebo 2,000 IU Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/3 (0%)		0/2 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Vitamin D 50,000 IU Weekly		Placebo 50,000 IU Weekly		Vitamin D 2,000 IU Daily		Placebo 2,000 IU Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		1/3 (33.3%)		2/2 (100%)		0/1 (0%)
Gastrointestinal disorders
Constipation	1/1 (100%)	1	0/3 (0%)	0	0/2 (0%)	0	0/1 (0%)	0
Dry Mouth	1/1 (100%)	1	1/3 (33.3%)	1	0/2 (0%)	0	0/1 (0%)	0
General disorders
Fatigue	1/1 (100%)	1	0/3 (0%)	0	2/2 (100%)	2	0/1 (0%)	0
Metabolism and nutrition disorders
Loss of Appetite	0/1 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0	0/1 (0%)	0
Musculoskeletal and connective tissue disorders
Weakness	1/1 (100%)	1	0/3 (0%)	0	0/2 (0%)	0	0/1 (0%)	0
Nervous system disorders
Headache	0/1 (0%)	0	1/3 (33.3%)	1	1/2 (50%)	1	0/1 (0%)	0

Limitations/Caveats

Low accrual led to this pilot study closing early. Accrual barriers included the 4-week minimum treatment time frame and narrow eligibility criteria. Small numbers prohibit meaningful analysis. Study provides important insights to recruitment.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.