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)
30 Years
N/A
Female
brca1 Mutation Carrier, brca2 Mutation Carrier, Ovarian Cancer
Trial Information
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)
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.
Inclusion 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)
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Prevention
Principal Investigator
Molly A. Brewer, MD, DVM, MS
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Arizona
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000396796
NCT ID:
NCT00098800
Start Date:
October 2004
Completion Date:
November 2006
Related Keywords:
- brca1 Mutation Carrier
- brca2 Mutation Carrier
- Ovarian Cancer
- ovarian epithelial cancer
- BRCA1 mutation carrier
- BRCA2 mutation carrier
- Ovarian Neoplasms
Name | Location |
|---|---|
| Arizona Cancer Center at University of Arizona Health Sciences Center | Tucson, Arizona 85724 |
