This study will evaluate women who are at increased genetic risk of developing ovarian cancer because they or a close relative have a mutation in the BRCA1 or BRCA2 gene (the genes that cause most of the genetic forms of ovarian cancer) or because they have a very strong family history of breast and/or ovarian cancer. The study has two aspects. There will be two groups of subjects in this study. One group of women who will have their ovaries and fallopian tubes surgically removed as a prophylactic (preventive) measure against developing ovarian/fallopian tube cancer. These women will be studied to determine whether the surgery does, in fact, decrease the risk of ovarian or tubal cancer and whether it decreases the risk of breast and other cancers. The tissue removed at surgery will also be investigated to see whether a new way of examining the ovaries after they are removed provides better information about cancer-related tissue changes. A second group of subjects will be women who choose not to have preventive surgery. These women will be followed closely to see if screening with multiple CA-125 blood testing over time (see below) can detect ovarian or tubal cancers in their early stages. Both groups of women will undergo examination of the process by which women decide upon various options for lowering their ovarian cancer risk and a detailed assessment of how their choice impacts their quality of life. It will look at how those who opt for ovariectomy feel after their surgery and how those who choose screening feel during the time of screening.

All participants will undergo the following procedures:

- Medical history, physical examination, and blood drawing upon entering the study, including blood samples for future ovarian cancer research.

- Screening mammogram, CA-125 blood test, and transvaginal ultrasound upon entering the study, with yearly repeat mammograms for all participants and yearly transvaginal ultrasound exams for women in the screening arm of the study. CA-125 is a protein found in the blood whose levels are elevated in most women with ovarian cancer. Transvaginal ultrasound is a way of taking pictures of the ovaries using sound waves. If the results of these tests are not normal, additional tests may be required to learn the reason for the abnormality.

- Questionnaires about personal, medical and family history, ovarian cancer risk factors, medication use, medical choices, and quality of life on entering the study, with repeat quality of life and medication use questionnaires every 6 months during the study period.

- Blood samples for follow-up visits and for CA-125 testing every 3 months as a screen for ovarian/fallopian tube cancers. Some blood from these samples will be saved for future ovarian cancer research.

- Semi-annual report during the duration of the study regarding health and quality of life changes that occur over the prior 6-month period.

Researchers will use the pattern and rate of change of CA-125 levels over time in women in the screening group to decide if more tests are needed to test for ovarian cancer. Women in the surgery portion will undergo surgical removal of their ovaries and fallopian tubes. The removed tissues will be studied using new methods to examine the cells more closely than usual, and a portion of the tissues will be stored for future research on ovarian cancer. This study is being conducted in collaboration with the Gynecologic Oncology Group (GOG), and is designated GOG Protocol 0199. Subjects may join the study at any participating GOG institution (http://www.gog.org).

Condition
Ovarian Neoplasms Breast Neoplasms

Further Study Details: 

Expected Total Enrollment:  30

We propose a nationwide, multi-institution, prospective cohort study of women at increased genetic risk of ovarian cancer. This project is a collaboration between the Clinical Genetics Branch of NCI's Intramural Research Program, the Gynecologic Oncology Group and the Cancer Genetics Network (CGN). This is a two-arm, non-randomized study of women contemplating prophylactic salpingo-oophorectomy (RRSO) in order to reduce their genetic risk of ovarian cancer. At-risk women will make the decision as to whether to undergo RRSO in consultation with their referring and primary physicians. All study participants will complete a battery of demographic, epidemiologic and psychosocial instruments upon study enrollment, and they will provide blood samples for research-based genetic testing for germline mutations in BRCA1/2, CA125 and serum storage.

Women who choose to undergo RRSO will have their surgical material collected under a standardized protocol that will govern its processing in the operating room and in the pathology laboratory. The presence of clinically occult primary cancers and histologic precursor lesions will be sought, and material will be banked for subsequent molecular studies. These subjects will be followed with quarterly CA125 levels and twice yearly administration of the psycho-social instruments.

Women who decline RRSO will enroll in a study of ovarian cancer screening, using longitudinal changes in CA125 [as assessed by a mathematical algorithm known as ROCA]. CA125 levels will be measured quarterly. Each CA125 determination will result in an estimate of the likelihood that the subject has ovarian cancer. For those in whom the suspicion is high, transvaginal ultrasound (TVUS) and gynecologic oncology consultation will be arranged. TVUS will be done, at a minimum, on an annual basis.

All women in both study groups will be monitored with quarterly CA125 and twice yearly administration of the psycho-social instruments. Primary outcomes will be the development of ovarian cancer, primary peritoneal carcinoma and breast cancer. Information on events related to estrogen deficiency will be collected, although the study is not powered to detect significant differences in these parameters. We intend to enroll approximately 1000 subjects in the RRSO group, and 2400 subjects in the screening group, each to include at least 400 BRCA1/2 mutation carriers.

This study represents a unique collaboration between intramural and extramural investigators responsible for studying hereditary ovarian cancer. These will be the first prospective data ever collected from high risk women which address the incidence of critical cancer endpoints and quality of life in these challenging patients.

Genders Eligible for Study:  Female

Criteria

INCLUSION CRITERIA
To be considered at increased genetic risk of ovarian cancer, subjects must have:
Age greater than or equal to 30;
No prior history of ovarian cancer, including low malignant potential cancers (LMP), or primary papillary serous carcinoma of the peritoneum;
Ovary status:
To be eligible for the RRSO arm of this study, subjects must have at least one intact ovary;
To be eligible for the screening arm of this study, which targets primary ovarian cancer as the endpoint, subjects must have at least one intact ovary;
To be eligible for the screening arm of this study, which targets primary peritoneal cancer as the endpoint, both ovaries and fallopian tubes must have been removed.
Satisfied one of the following additional criteria:
The family of the subject has a documented deleterious BRCA1 or BRCA2 mutation - either:
- the subject herself has tested positive for a BRCA1 or BRCA2 mutation; OR
-the subject has a first- or second-degree relative with a BRCA1 or BRCA2 mutation
OR
The family contains at least two ovarian and/or breast cancers among the subject or first- or second-degree relatives of the subject within the same lineage. This condition is satisfied by multiple primary cancers in the same person. Where breast cancer is required to meet this criterion, at least one breast cancer must be diagnosed prior to menopause (age at diagnosis less than or equal to 50 if age at menopause is unknown); OR
The subject is of Ashkenazi Jewish ethnicity with one first-degree or two second-degree relatives with breast and/or ovarian cancer. Where breast cancer is required to meet this criterion, at least one case must have been diagnosed prior to menopause (or at age less than or equal to 50, if age at menopause is unknown).
OR
The subject is of Ashkenazi ancestry and has had breast cancer herself. To meet this criterion, her breast cancer must have been diagnosed prior to menopause (age at diagnosis less than or equal to 50 if age at menopause is unknown).
OR
The probability of carrying a BRCA1/2 mutation given the family pedigree of breast and ovarian cancers exceeds 20% as calculated by BRCAPRO.
Signed an approved informed consent.
EXCLUSION CRITERIA
A first- or second-degree relative has a deleterious BRCA1/2 mutation, and the subject has tested NEGATIVE for the exact same mutation.
Women who are currently pregnant or planning pregnancy during the study.
Women who are participating in another ovarian cancer early detection trial (except for the ROCA study being run by the Cancer Genetics Network. Women who have enrolled in the ROCA study prior to GOG activating GOG 0199 and who subsequently choose to undergo surgery may enroll in the surgical arm of GOG 0199).
Women with psychiatric, psychological or other conditions which prevent fully informed consent.
Women with current untreated malignancy (excluding non-melanoma skin cancer).
Women with adjuvant radiation therapy or chemotherapy within the past 1 month (31 days).
Women who have been treated for prior metastatic malignant disease within the past 5 years.
Women who have undergone intraperitoneal surgery within the prior 3 months (includes laparoscopy).
Women with a history of any medical condition which places the subject at risk related to the need for donating blood for research purposes, e.g., chronic infectious diseases, severe anemia, hemophilia.

Maryland
      National Cancer Institute (NCI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  020268; 02-C-0268
Record last reviewed:  June 17, 2004
Last Updated:  November 23, 2004
Record first received:  August 8, 2002
ClinicalTrials.gov Identifier:  NCT00043472
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08