Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cancer
Conditions
Keywords
High Risk
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.
Interventions
DIETARY_SUPPLEMENTArm A: Vitamin D3 Group
DIETARY_SUPPLEMENTPlacebo
Sponsors
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Vitamin D 50,000 IU Weekly 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) | 1 |
| Placebo 50,000 IU Weekly If Vitamin D level is ≤ 30ng/ml at baseline, randomized to Placebo p.o. weekly until surgery (levels will be rechecked every 4 weeks) | 3 |
| Vitamin D 2,000 IU Daily 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) | 2 |
| Placebo 2,000 IU Daily If Vitamin D level is\>30ng/ml at baseline, randomized to Placebo p.o. daily until surgery (levels will be rechecked every 4 weeks) | 1 |
| Total | 7 |
Baseline characteristics
| Characteristic | Vitamin D 50,000 IU Weekly | Placebo 50,000 IU Weekly | Vitamin D 2,000 IU Daily | Placebo 2,000 IU Daily | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 3 Participants | 2 Participants | 1 Participants | 7 Participants |
| Region of Enrollment United States | 1 participants | 3 participants | 2 participants | 1 participants | 7 participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 2 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 1 | 1 / 3 | 2 / 2 | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 3 | 0 / 2 | 0 / 1 |
Outcome results
Primary
Other Surrogate Endpoint Biomarkers Markers of Cancer Prevention
Decrease in cellular proliferation measured by immunohistochemistry staining with KI67
Time frame: Up to 24 months
Population: 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.
Primary
The Outcomes That Will be Measured for the Primary Objectives of This Study Will be Surrogate Endpoint Biomarkers Markers of Cancer Prevention
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
Population: 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.
Secondary
Review of Standard Pathologic Evaluation With Specific Attention to Histologic Markers
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
Population: 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.
Secondary
Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement.
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vitamin D 50,000 IU Weekly | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Fatige grade 1 | 1 participants |
| Vitamin D 50,000 IU Weekly | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Constipation grade 1 | 1 participants |
| Vitamin D 50,000 IU Weekly | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Dry Mouth grade 1 | 1 participants |
| Vitamin D 50,000 IU Weekly | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Headache grade 1 | 0 participants |
| Vitamin D 50,000 IU Weekly | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Weakness grade 1 | 1 participants |
| Vitamin D 50,000 IU Weekly | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Hypercalcemia | 0 participants |
| Vitamin D 50,000 IU Weekly | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Loss of Appetite grade 1 | 0 participants |
| Placebo 50,000 IU Weekly | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Constipation grade 1 | 0 participants |
| Placebo 50,000 IU Weekly | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Loss of Appetite grade 1 | 1 participants |
| Placebo 50,000 IU Weekly | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Hypercalcemia | 0 participants |
| Placebo 50,000 IU Weekly | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Dry Mouth grade 1 | 1 participants |
| Placebo 50,000 IU Weekly | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Weakness grade 1 | 0 participants |
| Placebo 50,000 IU Weekly | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Headache grade 1 | 1 participants |
| Placebo 50,000 IU Weekly | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Fatige grade 1 | 0 participants |
| Vitamin D 2,000 IU Daily | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Loss of Appetite grade 1 | 0 participants |
| Vitamin D 2,000 IU Daily | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Fatige grade 1 | 0 participants |
| Vitamin D 2,000 IU Daily | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Headache grade 1 | 1 participants |
| Vitamin D 2,000 IU Daily | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Hypercalcemia | 0 participants |
| Vitamin D 2,000 IU Daily | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Dry Mouth grade 1 | 0 participants |
| Vitamin D 2,000 IU Daily | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Constipation grade 1 | 0 participants |
| Vitamin D 2,000 IU Daily | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Weakness grade 1 | 0 participants |
| Placebo 2,000 IU Daily | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Hypercalcemia | 0 participants |
| Placebo 2,000 IU Daily | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Weakness grade 1 | 0 participants |
| Placebo 2,000 IU Daily | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Constipation grade 1 | 0 participants |
| Placebo 2,000 IU Daily | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Headache grade 1 | 0 participants |
| Placebo 2,000 IU Daily | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Fatige grade 1 | 0 participants |
| Placebo 2,000 IU Daily | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Dry Mouth grade 1 | 0 participants |
| Placebo 2,000 IU Daily | Review of the Differences in the Types and Incidence of Toxicities Associated With Vitamin D3 Replacement. | Loss of Appetite grade 1 | 0 participants |