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

Sponsor

University of Arizona (Other)

Overall Status

Completed

CT.gov ID

NCT00098800

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Duration (Months)

1.6

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
brca1 Mutation Carrier brca2 Mutation Carrier Ovarian Cancer	Drug: fenretinide	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Masking:

Double

Primary Purpose:

Prevention

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 Start Date :

Oct 1, 2004

Actual Primary Completion Date :

Aug 1, 2006

Actual Study Completion Date :

Nov 1, 2006

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years and Older

Sexes Eligible for Study:

Female

Accepts 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)