Clinical trial NCT00017134: Fenretinide Followed by Surgery Compared With Surgery Alone in Preventing Ovarian Cancer in Patients at Increased Risk
Official title: An Exploratory Evaluation of Fenretinide (4-HPR) as a Chemopreventive Agent for Ovarian Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Ovarian Cancer
Keywords: ovarian epithelial cancer
Lead sponsor: GOG Foundation
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-05-07
Enrollment: 71
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: PREVENTION

Brief summary: RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development of cancer. It is not yet known whether fenretinide given before surgery is more effective in preventing ovarian cancer than surgery alone.

PURPOSE: Randomized clinical trial to compare the effectiveness of fenretinide followed by surgery with that of surgery alone in preventing ovarian cancer in patients who are at increased risk.

Detailed description: OBJECTIVES:

* Compare the frequency of histopathology markers or precursor lesions of the ovaries, including surface papillomatosis, invaginations, pseudostratification, and inclusion cysts, removed from patients at increased risk for ovarian cancer between those receiving fenretinide vs those undergoing immediate oophorectomy.
* Determine the relative abundance of markers of cell proliferation and apoptosis in cancer-prone ovaries of patients treated with fenretinide.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 arms.

* Arm I: Patients undergo prophylactic oophorectomy.
* Arm II: Patients receive oral fenretinide once daily for 27 days every 30 days for 6-8 weeks. Treatment continues in the absence of unacceptable toxicity or diagnosis of malignancy. After completion of fenretinide, patients undergo prophylactic oophorectomy.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 71 patients will be accrued for this study within 2 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Increased risk for ovarian cancer secondary to 1 of the following:

  * Evidence of a BRCA1 or BRCA2 genetic mutation
  * Family history of 1 or more first-degree relatives diagnosed with ovarian cancer prior to 50 years of age
  * Family history of 1 first-degree relative with ovarian cancer (any age) AND 1 or more first- or second-degree relatives diagnosed with breast or ovarian cancer
  * Personal history of breast cancer (at any age) AND 1 or more first- or second-degree relative diagnosed with breast or ovarian cancer at any age
* Meets any 1 of the following criteria:

  * Ashkenazi Jewish ethnicity with 1 first-degree or 2 second-degree relatives with breast\* and/or ovarian cancer
  * Ashkenazi Jewish ethnicity with diagnosed breast\* cancer in patient
  * Greater than 20% probability of carrying BRCA1/2 mutation with a family history of breast and ovarian cancer NOTE: \* Where breast cancer is required to meet this criteria, diagnosis must occur prior to menopause or at ≤ 50 years old if age at menopause is unknown
* Planned prophylactic oophorectomy
* Normal pelvic exam within the past 6 weeks

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* GOG 0-1

Life expectancy:

* At least 12 months

Hematopoietic:

* WBC at least 4,000/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Bilirubin no greater than 1.5 mg/dL
* SGOT no greater than 2 times upper limit of normal (ULN)

Renal:

* Creatinine no greater than 1.5 mg/dL OR
* Creatinine clearance at least 60 mL/min
* Triglyceride less than 2 times ULN (fasting)

Cardiovascular:

* No myocardial infarction within the past 3 months
* No active angina
* No unstable heart rhythms
* No clinically evident congestive heart failure

Other:

* No uncontrolled medical illness that would preclude study participation
* No uncontrolled diabetes
* No uncontrolled psychiatric illness
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective barrier contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* At least 3 months since prior chemotherapy

Endocrine therapy:

* At least 3 months since prior hormonal therapy
* At least 8 weeks since prior hormone replacement therapy
* At least 8 weeks since prior oral, injectable, or implantable contraceptives
* No concurrent hormonal therapy, including hormone replacement therapy

Radiotherapy:

* At least 3 months since prior radiotherapy
* No prior radiotherapy to pelvis for malignancy

Surgery:

* See Disease Characteristics

Other:

* At least 3 months since prior investigational treatment
* No concurrent nutritional supplements except a daily multivitamin with less than 25,000 IU of vitamin A
* No prior non-steroidal anti-inflammatory drugs (NSAIDs) on a regular (chronic or daily) basis within the past 6 months
* No concurrent NSAIDs on a regular (chronic or daily) basis
* Concurrent aspirin at a dose of 81 mg/day allowed

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center at UCLA
state: California
city: Aurora
country: United States
facility: Colorado Gynecologic Oncology Group P.C.
state: Colorado
city: Hartford
country: United States
facility: Helen and Harry Gray Cancer Center at Hartford Hospital
state: Connecticut
city: New Britain
country: United States
facility: George Bray Cancer Center at New Britain General Hospital
state: Connecticut
city: Fort Lauderdale
country: United States
facility: Michael & Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
state: Florida
city: Evanston
country: United States
facility: Evanston Northwestern Healthcare - Evanston Hospital
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent Indianapolis Hospital
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: Markey Cancer Center at University of Kentucky Chandler Medical Center
state: Kentucky
city: Royal Oak
country: United States
facility: William Beaumont Hospital - Royal Oak Campus
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center & Children's Hospital - Fairview
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Springfield
country: United States
facility: CCOP - Cancer Research for the Ozarks
state: Missouri
city: Springfield
country: United States
facility: St. John's Regional Health Center
state: Missouri
city: Springfield
country: United States
facility: Hulston Cancer Center at Cox Medical Center South
state: Missouri
city: St Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital
state: Missouri
city: Hackensack
country: United States
facility: CCOP - Northern New Jersey
state: New Jersey
city: Voorhees
country: United States
facility: Cancer Institute of New Jersey at Cooper - Voorhees
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Blumenthal Cancer Center at Carolinas Medical Center
state: North Carolina
city: Akron
country: United States
facility: McDowell Cancer Center at Akron General Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital Cancer Care
state: Ohio
city: Columbus
country: United States
facility: Mount Carmel Health - West Hospital
state: Ohio
city: Mayfield Heights
country: United States
facility: Hillcrest Cancer Center at Hillcrest Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Medical Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University Cancer Institute
state: Oregon
city: Allentown
country: United States
facility: Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
state: Pennsylvania
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Burlington
country: United States
facility: Fletcher Allen Health Care - University Health Center Campus
state: Vermont
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
Study officials:
affiliation: Fox Chase Cancer Center
name: Mary B. Daly, MD, PhD
role: STUDY_CHAIR
References: