RATIONALE: Screening tests may help doctors detect cancer cells early and plan more effective treatment for ovarian cancer.

PURPOSE: Screening trial to determine the significance of CA 125 levels in detecting ovarian cancer in participants who have a high genetic risk of developing ovarian cancer.

Condition	Treatment or Intervention
ovarian epithelial cancer	Procedure: screening intervention  Procedure: screening questionnaire  Procedure: study of high risk factors

Further Study Details: 

OBJECTIVES:

• Determine the feasibility of prospective ovarian cancer screening studies within the Cancer Genetics Network and other NCI ovarian programs for participants who are at high genetic risk for developing ovarian cancer.
• Identify the logistical issues of screening these participants and their solutions within this framework.
• Establish normal ranges and distributions of CA 125 values over time within and between high-risk participants, with subclassification by pre- or post-menopausal status, estrogen-replacement therapy usage, and prior prophylactic oophorectomy.
• Estimate the specificity and positive predictive value of the "risk of ovarian cancer algorithm" (ROCA) suitable for designing a definitive trial of screening for ovarian cancer in high-risk participants.
• Establish a longitudinal serum and plasma biorepository for retrospective evaluation of other promising biomarkers with special relevance to inherited ovarian and breast cancer risk.

OUTLINE: This is a multicenter study. Participants with 1 or 2 ovaries are assigned to group A, whereas participants with prior prophylactic bilateral oophorectomy are assigned to group B (closed to accrual as of 10/18/04).

At baseline, participants who are not eligible by BRCA mutation criteria or family history criteria undergo BRCAPRO evaluation. Participants in both groups complete a questionnaire requesting demographic information and a personal and family health history at baseline and a questionnaire requesting hospitalization or cancer diagnosis information after each blood test. Participants in both groups also complete health status questionnaires once every 3 months for 1-3 years. Participants undergo blood draws for measurement of CA 125 levels once every 3 months for 1-3 years. For each CA 125 measurement, the risk of ovarian cancer algorithm (ROCA) is calculated.

Group A (1 or 2 ovaries at baseline):

• Participants are assigned to 1 of 2 subgroups based on ROCA.
• Subgroup A1: Participants with normal-risk for ovarian cancer (ROCA less than 1%) continue CA 125 screening as above.
• Subgroup A2: Participants with intermediate-risk for ovarian cancer (ROCA more than 1% but less than 10%) or elevated-risk for ovarian cancer (ROCA more than 10%) undergo transvaginal sonography (TVS). Participants with elevated-risk undergo an additional blood draw for a confirmatory CA 125 level prior to TVS. Participants with normal TVS continue CA 125 screening as above. Participants with abnormal TVS are referred to a gynecologic oncologist who decides whether standard clinical intervention for potential ovarian cancer is needed. Participants who are not referred for standard clinical intervention continue CA 125 screening as above. Participants who are referred for standard clinical intervention, have at least 1 ovary remaining, and are found to have no malignancy continue CA 125 screening as above. Participants who are referred for standard clinical intervention, are found to have no malignancy, and then undergo prophylactic bilateral oophorectomy proceed to CA 125 screening as in group B below. Participants who are referred for standard clinical intervention and are found to have malignancy are taken off study.

Group B (no ovaries at baseline) (closed to accrual as of 10/18/04):

• Participants are assigned to 1 of 2 subgroups based on ROCA.
• Subgroup B1: Participants with normal-risk for ovarian cancer (ROCA less than 5%) continue CA 125 screening as above.
• Subgroup B2: Participants with elevated-risk for ovarian cancer (ROCA more than 5%) undergo an additional blood draw for a confirmatory CA 125 level and are then referred to a gynecologic oncologist who decides whether standard clinical intervention for potential ovarian cancer is needed. Participants who are not referred for standard clinical intervention continue CA 125 screening as above. Participants who are referred for standard clinical intervention and are not found to have malignancy continue CA 125 screening as above. Participants who are referred for standard clinical intervention and are found to have malignancy are taken off study. Patients are followed for clinical diagnosis for 1 additional year.

PROJECTED ACCRUAL: Approximately 2,430 participants will be accrued for this study within 12 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Participant meet the criteria for one of the following conditions:
• Participant has tested positive for BRCA1 or BRCA2 mutation or has a first- or second-degree relative with a BRCA1 or BRCA2 mutation
• At least 2 ovarian or breast cancers (including ductal carcinoma in situ) have occurred among the participant and her first- and second-degree relatives within the same lineage
• Condition may be satisfied by multiple primary cancers in the same person
• Where breast cancer is required to meet this criterion, at least 1 breast cancer patient must have been pre-menopausal (age 50 and under at diagnosis if age at menopause unknown)
• Participant is of Ashkenazi Jewish ethnicity and either has had breast cancer or has 1 first-degree or 2 second-degree relatives with breast cancer (including ductal carcinoma in situ) or ovarian cancer
• Where breast cancer is required to meet this criterion, at least 1 breast cancer patient must have been pre-menopausal (age 50 and under at diagnosis if age at menopause unknown)
• Probability of carrying a BRCA1 or BRCA2 mutation exceeds 20% as calculated by BRCAPRO, given family pedigree of breast cancer (including ductal carcinoma in situ) and ovarian cancer
• Participant must have no prior or concurrent ovarian cancer (including low malignant potential (LMP) cancers) or primary papillary serous carcinoma of the peritoneum
• Participant must not be negative for the same BRCA1 or BRCA2 mutation for which a first- or second-degree relative has tested positive
• Participants who test negative for BRCA1 or BRCA2 mutation are still eligible if the pedigree or BRCAPRO criteria are satisfied, including Ashkenazi women who test negative for the three founder mutations
• Documentation of family history is by participant's self-report
• In relatives, ovarian cancer is defined as invasive ovarian epithelial cancers, fallopian tube cancers, or primary papillary serous carcinoma of the peritoneum
• Germ cell or granulosa tumors or LMP ovarian cancers do not qualify
• First- and second-degree relatives include half siblings of the participant or her first-degree relative

PATIENT CHARACTERISTICS: Age:

• 30 and over

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• No hemophilia or other bleeding disorders
• No serious anemia

Hepatic:

• Not specified

Renal:

• Not specified

Pulmonary:

• No emphysema

Other:

• Not pregnant
• Fertile patients must use effective contraception
• No psychiatric, psychological, or other conditions that would preclude informed consent
• No concurrent untreated malignancy except nonmelanoma skin cancer
• No medical conditions that would preclude blood draws during study
• No chronic infectious disease

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• At least 3 months since prior adjuvant anticancer chemotherapy

Endocrine therapy:

• Prior or concurrent adjuvant hormonal therapies (e.g., tamoxifen, leuprolide, or goserelin) allowed
• Concurrent hormonal therapies (e.g., tamoxifen) for prevention allowed

Radiotherapy:

• At least 3 months since prior adjuvant anticancer radiotherapy

Surgery:

• At least 3 months since prior intraperitoneal surgery (laparoscopy or laparotomy)
• No prior prophylactic oophorectomy

Other:

• At least 5 years since prior non-hormonal treatment for metastatic malignancy
• No concurrent participation in other ovarian cancer early detection trials

Alabama
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294-4410,  United States; Recruiting
California
      Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center, Orange,  California,  92868,  United States; Recruiting
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94115,  United States; Recruiting
Colorado
      University of Colorado Cancer Center at University of Colorado Health Sciences Center, Aurora,  Colorado,  80010,  United States; Recruiting
District of Columbia
      Lombardi Cancer Center at Georgetown University Medical Center, Washington,  District of Columbia,  20007,  United States; Recruiting
Georgia
      Winship Cancer Institute of Emory University, Atlanta,  Georgia,  30322,  United States; Recruiting
Iowa
      John Stoddard Cancer Center at Iowa Methodist Medical Center, Des Moines,  Iowa,  50309,  United States; Recruiting
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231-2410,  United States; Recruiting
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
      Massachusetts General Hospital Cancer Center, Boston,  Massachusetts,  02114,  United States; Recruiting
Nebraska
      Creighton University School of Medicine, Omaha,  Nebraska,  68178,  United States; Recruiting
North Carolina
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27705,  United States; Recruiting
      Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill,  North Carolina,  27599-7295,  United States; Recruiting
Pennsylvania
      Abramson Cancer Center at the University of Pennsylvania, Philadelphia,  Pennsylvania,  19104-4283,  United States; Recruiting
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111-2497,  United States; Recruiting
      UPMC Cancer Center at Magee-Womens Hospital, Pittsburgh,  Pennsylvania,  15213,  United States; Recruiting
Texas
      Baylor College of Medicine, Houston,  Texas,  77030,  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,  75390-9032,  United States; Recruiting
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78284-7811,  United States; Recruiting
Utah
      Huntsman Cancer Institute at University of Utah, Salt Lake City,  Utah,  84112-5550,  United States; Recruiting
Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States; Recruiting

Study chairs or principal investigators

Steven J. Skates, PhD,  Study Chair,  Massachusetts General Hospital   

Study ID Numbers:  CDR0000069397; MGH-000084; NCT00039559
Record last reviewed:  December 2004
Last Updated:  April 4, 2005
Record first received:  June 6, 2002
ClinicalTrials.gov Identifier:  NCT00039559
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08