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Fenretinide in Preventing Ovarian Cancer in Participants Who Are at High Risk for Developing Ovarian Cancer and Planning to Undergo Surgery to Remove the Ovaries

Primary Purpose

brca1 Mutation Carrier, brca2 Mutation Carrier, Ovarian Cancer

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
fenretinide
Sponsored by
University of Arizona
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional prevention trial for brca1 Mutation Carrier focused on measuring ovarian epithelial cancer, BRCA1 mutation carrier, BRCA2 mutation carrier

Eligibility Criteria

30 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: At high risk for developing ovarian cancer, meeting 1 of the following criteria: Family history of ovarian cancer, defined as ≥ 1 first-degree relative diagnosed with ovarian cancer before 50 years of age Family history of ovarian cancer, defined as ≥ 1 first-degree relative diagnosed with ovarian cancer at any age AND ≥ 1 first- or second-degree relative diagnosed with breast or ovarian cancer at any age Positive BRCA1/BRCA2 test Planning to undergo prophylactic bilateral oophorectomy PATIENT CHARACTERISTICS: Age 30 and over Performance status Zubrod 0-1 Life expectancy At least 12 months Hematopoietic Not specified Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN) SGOT ≤ 1.5 times ULN Alkaline phosphatase ≤ 1.5 times ULN No history of liver disease* No cholestatic jaundice No hepatic adenomas NOTE: *For patients undergoing contrast enhanced ultrasound Renal BUN normal Creatinine normal Cardiovascular No history of a congenital heart defect creating a bi-directional or right-to-left shunt* No history of congestive heart failure* No thrombophlebitis No thromboembolic disease No cerebral vascular disease No coronary artery disease NOTE: *For patients undergoing contrast enhanced ultrasound Pulmonary No history of pulmonary hypertension* No history of pulmonary emboli* No history of severe emphysema* NOTE: *For patients undergoing contrast enhanced ultrasound Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception Thyroid stimulating hormone normal T4 normal Triglycerides ≤ 1.5 times ULN No malignancy within the past 5 years except breast cancer or basal cell or squamous cell skin cancer No evidence of recurrent disease No known or suspected hypersensitivity to blood, blood products, or albumin No undiagnosed genital bleeding No history of pancreatitis No uncontrolled diabetes No other severe underlying chronic disease No concurrent alcohol use (> 3 drinks/day or equivalent) PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy At least 3 months since prior chemotherapy for breast cancer Endocrine therapy No concurrent selective estrogen-receptor modulators, including raloxifene No concurrent aromatase inhibitors Radiotherapy Not specified Surgery See Disease Characteristics Other More than 3 months since prior therapeutic oral or topical vitamin A derivatives (e.g., isotretinoin) No other concurrent investigational agents No concurrent cyclooxygenase-2 (COX-2) inhibitors No concurrent oral vitamin A or ascorbic acid (vitamin C) supplements > recommended daily requirement (10,000 IU for vitamin A and 75 mg for vitamin C)

Sites / Locations

  • Arizona Cancer Center at University of Arizona Health Sciences Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
December 8, 2004
Last Updated
March 23, 2010
Sponsor
University of Arizona
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00098800
Brief Title
Fenretinide in Preventing Ovarian Cancer in Participants Who Are at High Risk for Developing Ovarian Cancer and Planning to Undergo Surgery to Remove the Ovaries
Official Title
A Multicenter Randomized Double-Blinded Trial for Chemoprevention of Ovarian Cancer: Modulation of Biomarkers and Spectral Properties Using Contrast Enhanced Ultrasound in High-Risk Women Using Fenretinide (4-HPR)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2006
Overall Recruitment Status
Completed
Study Start Date
October 2004 (undefined)
Primary Completion Date
August 2006 (Actual)
Study Completion Date
November 2006 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
University of Arizona
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of fenretinide may prevent ovarian cancer. PURPOSE: This randomized clinical trial is studying how well fenretinide works in preventing ovarian cancer in participants who are at high risk of developing ovarian cancer and planning to undergo surgery to remove the ovaries.
Detailed Description
OBJECTIVES: Primary Compare the induction of apoptosis (as determined by TUNEL) in the ovarian epithelial and stromal cells of participants at high risk for ovarian cancer treated with fenretinide vs placebo. Secondary Compare modulation of several intermediate markers (TGFβ, BAX, Ki-67, ER, PR, RARβ, TGFβRI, TGFβRII, p21, p53, FAS, and FASL) in participants treated with these regimens. Compare early microvascular changes, using contrast-enhanced ultrasound, in participants treated with these drugs. Determine whether the use of contrast agents could indicate changes in ovarian size and architecture that may be assessed as potential surrogates for preventive effect in these participants. Determine the feasibility of future chemoprevention trials for ovarian cancer. Determine the toxicity of fenretinide in these participants. Compare the microvascularity index and ovarian volume of participants treated with these drugs. Correlate areas of increased microvascularity and other abnormalities with pathology findings obtained at oophorectomy in participants treated with these drugs. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Participants are randomized to 1 of 2 treatment arms. Arm I: Participants receive oral fenretinide once daily. Arm II: Participants receive oral placebo once daily. In both arms, treatment continues for 6-8 weeks in the absence of unacceptable toxicity. Within 5 days after completion of fenretinide or placebo, participants undergo bilateral salpingo-oophorectomy. Participants are followed at 6 weeks. PROJECTED ACCRUAL: A total of 40 participants (20 per treatment arm) will be accrued for this study within 4 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
brca1 Mutation Carrier, brca2 Mutation Carrier, Ovarian Cancer
Keywords
ovarian epithelial cancer, BRCA1 mutation carrier, BRCA2 mutation carrier

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Masking
Double
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
fenretinide

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: At high risk for developing ovarian cancer, meeting 1 of the following criteria: Family history of ovarian cancer, defined as ≥ 1 first-degree relative diagnosed with ovarian cancer before 50 years of age Family history of ovarian cancer, defined as ≥ 1 first-degree relative diagnosed with ovarian cancer at any age AND ≥ 1 first- or second-degree relative diagnosed with breast or ovarian cancer at any age Positive BRCA1/BRCA2 test Planning to undergo prophylactic bilateral oophorectomy PATIENT CHARACTERISTICS: Age 30 and over Performance status Zubrod 0-1 Life expectancy At least 12 months Hematopoietic Not specified Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN) SGOT ≤ 1.5 times ULN Alkaline phosphatase ≤ 1.5 times ULN No history of liver disease* No cholestatic jaundice No hepatic adenomas NOTE: *For patients undergoing contrast enhanced ultrasound Renal BUN normal Creatinine normal Cardiovascular No history of a congenital heart defect creating a bi-directional or right-to-left shunt* No history of congestive heart failure* No thrombophlebitis No thromboembolic disease No cerebral vascular disease No coronary artery disease NOTE: *For patients undergoing contrast enhanced ultrasound Pulmonary No history of pulmonary hypertension* No history of pulmonary emboli* No history of severe emphysema* NOTE: *For patients undergoing contrast enhanced ultrasound Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception Thyroid stimulating hormone normal T4 normal Triglycerides ≤ 1.5 times ULN No malignancy within the past 5 years except breast cancer or basal cell or squamous cell skin cancer No evidence of recurrent disease No known or suspected hypersensitivity to blood, blood products, or albumin No undiagnosed genital bleeding No history of pancreatitis No uncontrolled diabetes No other severe underlying chronic disease No concurrent alcohol use (> 3 drinks/day or equivalent) PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy At least 3 months since prior chemotherapy for breast cancer Endocrine therapy No concurrent selective estrogen-receptor modulators, including raloxifene No concurrent aromatase inhibitors Radiotherapy Not specified Surgery See Disease Characteristics Other More than 3 months since prior therapeutic oral or topical vitamin A derivatives (e.g., isotretinoin) No other concurrent investigational agents No concurrent cyclooxygenase-2 (COX-2) inhibitors No concurrent oral vitamin A or ascorbic acid (vitamin C) supplements > recommended daily requirement (10,000 IU for vitamin A and 75 mg for vitamin C)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Molly A. Brewer, MD, DVM, MS
Organizational Affiliation
University of Arizona
Official's Role
Principal Investigator
Facility Information:
Facility Name
Arizona Cancer Center at University of Arizona Health Sciences Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724-5024
Country
United States

12. IPD Sharing Statement

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Fenretinide in Preventing Ovarian Cancer in Participants Who Are at High Risk for Developing Ovarian Cancer and Planning to Undergo Surgery to Remove the Ovaries

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