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

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.

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)