RATIONALE: Surgery to remove the fallopian tubes and ovaries may decrease the risk of ovarian cancer and may improve quality of life in women who are at increased genetic risk. Monitoring CA 125 levels may help doctors detect cancer cells early and plan more effective treatment for ovarian cancer.

PURPOSE: Screening trial to study the effectiveness of surgery to remove the fallopian tubes and ovaries combined with monitoring of CA 125 levels in participants who are at increased genetic risk for ovarian cancer.

Condition	Treatment or Intervention
ovarian epithelial cancer	Procedure: annual screening  Procedure: cancer prevention intervention  Procedure: comparison of screening methods  Procedure: conventional surgery  Procedure: evaluation of cancer risk factors  Procedure: long-term screening  Procedure: screening intervention  Procedure: screening questionnaire  Procedure: study of high risk factors  Procedure: study of physiologic variables  Procedure: surgery

Further Study Details: 

OBJECTIVES: Primary

• Compare the prospective incidence of ovarian cancer, breast cancer, fallopian tube cancer, primary peritoneal cancer, and all cancer in participants at increased genetic risk of ovarian cancer who undergo risk-reducing salpingo-oophorectomy (RRSO) or CA 125 screening.
• Determine the prevalence of clinically occult ovarian cancer and fallopian tube cancer and precursor lesions in participants who undergo RRSO.
• Determine the positive predictive value and specificity of the Risk of Ovarian Cancer Algorithm (ROCA) based on serial CA 125 measurements for ovarian cancer in participants who do not undergo RRSO.
• Compare quality of life, sexual functioning, frequency of menopausal symptoms, depression, anxiety, cancer worry, and concerns associated with familial risk of ovarian cancer in participants who undergo RRSO vs screening.
• Compare changes in these quality of life parameters over time in these participants.
• Establish a longitudinal serum, plasma, and tissue repository for the evaluation of promising biomarkers and genetic alterations with relevance to familial ovarian and breast cancer risk.

Secondary

• Determine patterns of use of medications (e.g., tamoxifen, raloxifene, estrogen or hormonal replacement therapy, alendronate, or vaginal estrogens) that may alter the risk of important medical outcomes (e.g., cancer endpoints or estrogen deficiency disorders) in these participants.
• Monitor overall mortality and the incidence of various disease states that complicate long-term estrogen deficiency (e.g., osteoporosis, skeletal fractures, coronary artery disease, or myocardial infarction) in these participants.
• Monitor these participants' and their health care providers' adherence to recommendations regarding the management of non-oncologic morbidity related to premature menopause.
• Analyze the factors (regarding cancer risk reduction and screening activities) that influence a woman's choice between RRSO vs screening.
• Establish normal ranges and distributions within and between high-risk participants for CA 125 values over time, with sub-classification by pre/postmenopausal status, HRT usage, RRSO status, and other risk factors.

OUTLINE: This is a multicenter study. Participants choose 1 of 2 screening/prevention groups.

• Group I (screening): Participants undergo genetic risk, medical and ovarian cancer risk factor, and quality of life (QOL) assessment; transvaginal ultrasound (TVUS); and CA 125 measurement. CA 125 is measured every 3 months and the Risk of Ovarian Cancer Algorithm (ROCA) is determined. QOL is assessed every 6 months. TVUS is repeated annually (unless ovaries have been removed) as is a mammogram. If screening tests are abnormal, TVUS may be repeated and laparotomy/laparoscopy may be performed if a malignancy is suspected or a benign finding requires surgery.
• Group II (risk-reducing surgery): Participants undergo genetic risk, medical and ovarian cancer risk factor, and QOL assessment; TVUS; and CA 125 measurement. Participants then undergo risk-reducing salpingo-oophorectomy (RRSO). CA 125 is measured and ROCA calculated every 3 months. QOL is assessed every 6 months and a mammogram is performed annually. Abnormal screening results are treated as in group I. Participants in group I who decide to undergo RRSO may cross-over to group II at any time.

QOL is assessed in both groups every 6 months for 3 years.

PROJECTED ACCRUAL: Approximately 3,400 participants (2,400 for group I and 1,000 for group II) will be accrued for this study within 2 years.

Ages Eligible for Study:  30 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• At increased genetic risk of ovarian cancer
• No prior history of ovarian cancer, including low malignant potential cancers, or primary papillary serous carcinoma of the peritoneum
• Must have one of the following as ovary status:
• At least 1 intact ovary (for risk-reducing salpingo-oophorectomy group or screening group with primary ovarian cancer as endpoint)
• Both ovaries and fallopian tubes removed while participating in GOG-0199 (for screening group with primary peritoneal cancer as endpoint)
• Must meet 1 of the following criteria:
• Documented deleterious BRCA1 or BRCA2 mutation in either participant or first- or second-degree* relative
• Participants not testing positive for the exact same deleterious BRCA1 or BRCA2 mutation of their relative are ineligible
• Family contains at least 2 ovarian and/or breast cancers among the participant or first- or second-degree* relatives within the same lineage
• Multiple primary cancers in same person satisfies this criterion
• At least 1 breast cancer must be premenopausal (age 50 or under at diagnosis if age at menopause unknown)
• Participant is of Ashkenazi Jewish ethnicity with 1 first-degree* or 2 second-degree* relatives with breast and/or ovarian cancer
• At least 1 breast cancer must be premenopausal (age 50 or under at diagnosis if age at menopause unknown)
• Participant is of Ashkenazi ancestry and has had premenopausal breast cancer
• Probability of carrying a BRCA1/2 mutation given the family pedigree of breast and ovarian cancer exceeds 20% as calculated by BRCAPRO NOTE: *First- or second-degree relative may include half-siblings of the participant or a first-degree relative.
• Ovarian cancer* in relatives may include any of the following:
• Invasive ovarian epithelial cancer
• Fallopian tube cancer
• Primary papillary serous carcinoma of the peritoneum NOTE: *Germ cell tumors, granulosa cell tumors, or ovarian tumors of low malignant potential not considered as ovarian cancer
• Prior history of breast cancer is allowed and may include any of the following:
• Ductal carcinoma in situ
• Positive regional lymph nodes (loco-regional disease)
• No bilateral oophorectomy performed before study entry
• Must be willing to disclose BRCA mutation status (if known) or willing to be tested for BRCA mutation (if not previously tested)

PATIENT CHARACTERISTICS: Age

• 30 and over

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Other

• Not pregnant or planning pregnancy
• No psychiatric, psychological, or other conditions that would preclude informed consent
• No prior medical condition (e.g., chronic infectious disease, severe anemia, or hemophilia) that would preclude donating blood for research purposes
• No prior metastatic malignant disease requiring therapy within the past 5 years
• No concurrent untreated malignancy except nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• At least 1 month since prior adjuvant chemotherapy
• No concurrent chemotherapy

Endocrine therapy

• Concurrent adjuvant hormonal therapy (e.g., tamoxifen, raloxifene, or arimidex) allowed
• Concurrent hormonal therapy (e.g., tamoxifen, raloxifene, or hormone replacement therapy) for cancer prevention, management of cardiovascular or bone disorders related to estrogen deficiency, or treatment of menopausal symptoms allowed

Radiotherapy

• At least 1 month since prior adjuvant radiotherapy
• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• At least 3 months since prior intraperitoneal surgery (including laparoscopy)

Other

• No concurrent participation in another ovarian cancer early detection trial except the Cancer Genetics Network's Risk of Ovarian Cancer Algorithm trial (if enrolled prior to entry into this study)
• Concurrent participation in a chemoprevention trial allowed

Alabama
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294,  United States; Recruiting
Arizona
      Arizona Cancer Center at University of Arizona Health Sciences Center, Tucson,  Arizona,  85724,  United States; Recruiting
      Mayo Clinic Scottsdale, Scottsdale,  Arizona,  85259,  United States; Recruiting
Arkansas
      Arkansas Cancer Research Center at University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States; Recruiting
California
      Glendale Memorial Hospital Comprehensive Cancer Center, Glendale,  California,  91204,  United States; Recruiting
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States; Recruiting
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033-0804,  United States; Recruiting
      Women's Cancer Center - Los Gatos, Los Gatos,  California,  95032,  United States; Recruiting
Colorado
      Rocky Mountain Cancer Centers - Denver Midtown, Denver,  Colorado,  80218,  United States; Recruiting
      University of Colorado Cancer Center at University of Colorado Health Sciences Center, Aurora,  Colorado,  80010,  United States; Recruiting
Connecticut
      Helen and Harry Gray Cancer Center at Hartford Hospital, Hartford,  Connecticut,  06102-5037,  United States; Recruiting
      New Britain General Hospital, New Britain,  Connecticut,  06050,  United States; Recruiting
      Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center, Hartford,  Connecticut,  06105,  United States; Recruiting
      Yale Comprehensive Cancer Center, New Haven,  Connecticut,  06520,  United States; Recruiting
District of Columbia
      Washington Cancer Institute at Washington Hospital Center, Washington,  District of Columbia,  20010,  United States; Recruiting
Florida
      Bayfront Medical Center, Saint Petersburg,  Florida,  33701,  United States; Recruiting
      Ella Milbank Foshay Cancer Center at Jupiter Medical Center, Jupiter,  Florida,  33458,  United States; Recruiting
      Florida Gynecologic Oncology - Fort Myers, Fort Myers,  Florida,  33901,  United States; Recruiting
      Michael & Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital, Fort Lauderdale,  Florida,  33308,  United States; Recruiting
      University of Miami Sylvester Comprehensive Cancer Center, Miami,  Florida,  33136,  United States; Recruiting
Hawaii
      MBCCOP - Hawaii, Honolulu,  Hawaii,  96813,  United States; Recruiting
      Tripler Army Medical Center, Honolulu,  Hawaii,  96859-5000,  United States; Recruiting
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States; Recruiting
      CCOP - Evanston, Evanston,  Illinois,  60201,  United States; Recruiting
      Rush University Medical Center, Chicago,  Illinois,  60612,  United States; Recruiting
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting
Iowa
      Holden Comprehensive Cancer Center at University of Iowa, Iowa City,  Iowa,  52242-1002,  United States; Recruiting
Kansas
      Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center, Kansas City,  Kansas,  66160-7357,  United States; Recruiting
Louisiana
      Ochsner Cancer Institute at Ochsner Clinic Foundation, New Orleans,  Louisiana,  70121,  United States; Recruiting
Maryland
      Cancer Center at Greater Baltimore Medical Center, Baltimore,  Maryland,  21204,  United States; Recruiting
      Clinical Genetics Branch, Rockville,  Maryland,  20892,  United States; Recruiting
      Harry and Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center, Baltimore,  Maryland,  21237,  United States; Recruiting
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231-2410,  United States; Recruiting
      Union Memorial Hospital, Baltimore,  Maryland,  21218,  United States; Recruiting
      Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support, Bethesda,  Maryland,  20892-1182,  United States; Recruiting
Massachusetts
      Cancer Center at Tufts - New England Medical Center, Boston,  Massachusetts,  02111,  United States; Recruiting
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
      United Hospital, Saint Paul,  Minnesota,  55102,  United States; Recruiting
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States; Recruiting
Missouri
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States; Recruiting
      Ellis Fischel Cancer Center at University of Missouri - Columbia, Columbia,  Missouri,  65203,  United States; Recruiting
Nebraska
      Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha, Omaha,  Nebraska,  68114-4199,  United States; Recruiting
New Hampshire
      Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon,  New Hampshire,  03756-0002,  United States; Recruiting
New Jersey
      Cancer Institute of New Jersey at the Cooper University Hospital, Voorhees,  New Jersey,  08043,  United States; Recruiting
      Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School, New Brunswick,  New Jersey,  08903,  United States; Recruiting
      Jersey Shore Cancer Center at Jersey Shore University Medical Center, Neptune,  New Jersey,  07754-0397,  United States; Recruiting
New Mexico
      University of New Mexico Cancer Research and Treatment Center, Albuquerque,  New Mexico,  87131-5636,  United States; Recruiting
New York
      Long Island Cancer Center at Stony Brook University Hospital, Stony Brook,  New York,  11794,  United States; Recruiting
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting
      NYU Cancer Institute at New York University Medical Center, New York,  New York,  10016,  United States; Recruiting
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States; Recruiting
North Carolina
      Blumenthal Cancer Center at Carolinas Medical Center, Charlotte,  North Carolina,  28203,  United States; Recruiting
      Comprehensive Cancer Center at Moore Regional Hospital, Pinehurst,  North Carolina,  28374,  United States; Recruiting
      Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill,  North Carolina,  27599-7295,  United States; Recruiting
Ohio
      Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University, Columbus,  Ohio,  43210-1240,  United States; Recruiting
      Charles M. Barrett Cancer Center at University Hospital, Cincinnati,  Ohio,  45219,  United States; Recruiting
      Hillcrest Cancer Center at Hillcrest Hospital, Mayfield Heights,  Ohio,  44124,  United States; Recruiting
      Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University, Cleveland,  Ohio,  44106-5065,  United States; Recruiting
      MetroHealth's Cancer Care Center at MetroHealth Medical Center, Cleveland,  Ohio,  44109,  United States; Recruiting
      Mount Carmel West Hospital, Columbus,  Ohio,  43222,  United States; Recruiting
      Riverside Methodist Hospital Cancer Care, Columbus,  Ohio,  43214-3998,  United States; Recruiting
Oklahoma
      Cancer Care Associates, Tulsa,  Oklahoma,  74133,  United States; Recruiting
      Oklahoma University Medical Center, Oklahoma City,  Oklahoma,  73190,  United States; Recruiting
Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97239-3098,  United States; Recruiting
      Salem Hospital Regional Cancer Center, Salem,  Oregon,  97309-5014,  United States; Recruiting
Pennsylvania
      UPMC Cancer Center at Magee-Womens Hospital, Pittsburgh,  Pennsylvania,  15213,  United States; Recruiting
Rhode Island
      Women and Infants Hospital of Rhode Island, Providence,  Rhode Island,  02905,  United States; Recruiting
South Dakota
      Rapid City Regional Hospital, Rapid City,  South Dakota,  57709,  United States; Recruiting
      Sioux Valley Hospital and University of South Dakota Medical Center, Sioux Falls,  South Dakota,  57117-5039,  United States; Recruiting
Tennessee
      Baptist Centers for Cancer Care, Memphis,  Tennessee,  38120,  United States; Recruiting
      Southeast Gynecologic Oncology Associates, Knoxville,  Tennessee,  37917,  United States; Recruiting
Texas
      Harrington Cancer Center, Amarillo,  Texas,  79106,  United States; Recruiting
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030-4009,  United States; Recruiting
      Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas,  Texas,  75390,  United States; Recruiting
      University of Texas Medical Branch, Galveston,  Texas,  77555-0209,  United States; Recruiting
Vermont
      Fletcher Allen Health Care - Medical Center Hospital of Vermont Campus, Burlington,  Vermont,  05401,  United States; Recruiting
Virginia
      Cancer Center at the University of Virginia, Charlottesville,  Virginia,  22908,  United States; Recruiting
      Massey Cancer Center at Virginia Commonwealth University, Richmond,  Virginia,  23298-0037,  United States; Recruiting
Wisconsin
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-6164,  United States; Recruiting

Study chairs or principal investigators

Mark H. Greene, MD,  Study Chair,  Clinical Genetics Branch   

Study ID Numbers:  CDR0000257695; GOG-0199; NCI-02-C-0268; NCT00049049
Record last reviewed:  December 2004
Last Updated:  April 4, 2005
Record first received:  November 12, 2002
ClinicalTrials.gov Identifier:  NCT00049049
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08