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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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brca1 Mutation Carrier, brca2 Mutation Carrier, Ovarian Cancer

Intervention / Treatment
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* Drug: fenretinide


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: fenretinide|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ovarian epithelial cancer, BRCA1 mutation carrier, BRCA2 mutation carrier