Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Related Information
Registry Information

Alternate Title

Screening Study of Surgery and CA 125 Levels in Participants at Increased Genetic Risk of Ovarian Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs No phase specified Prevention, Screening Closed 30 and over NCI GOG-0199 NCI-02-C-0268, NCT00049049

Objectives

Primary

1. 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.
2. Determine the prevalence of clinically occult ovarian cancer and fallopian tube cancer and precursor lesions in participants who undergo RRSO.
3. 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.
4. 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.
5. Compare changes in these quality of life parameters over time in these participants.
6. 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

1. 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.
2. 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.
3. Monitor these participants' and their health care providers' adherence to recommendations regarding the management of non-oncologic morbidity related to premature menopause.
4. Analyze the factors (regarding cancer risk reduction and screening activities) that influence a woman's choice between RRSO vs screening.
5. 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.

Entry 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



• At least 1 intact ovary



• 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-degree relatives may include half-siblings of the participant]

   [Note: **Breast cancer in first- or second-degree male relatives is allowed]

   [Note: ***For patients whose eligibility is based on the combination of Ashkenazi heritage, the Ashkenazi heritage must be on the same side of the family as are the breast and ovarian cancers]




• 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 are not considered 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)

Prior/Concurrent Therapy:

Biologic therapy

• No prior anticancer biologic therapy

Chemotherapy

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

Endocrine therapy

• Concurrent adjuvant hormonal therapy (e.g., tamoxifen, raloxifene, anastrozole, letrozole, exemestane, or leuprolide acetate) 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

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

Expected Enrollment

A total of 2,332 participants will be accrued for this study.

Outcomes

Incidence of reported occurrences of breast, ovarian, fallopian tube, and peritoneal cancer 5 years after study completion
Prevalence of clinically occult ovarian cancer and precursor lesions in prophylactically-excised ovaries and fallopian tubes by using standardized tissue processing and histological examination of surgical tissue after completion of accrual to the surgical arm of this trial (projected for December 2006)
Quantify the positive predictive value and specificity of the risk of ovarian cancer screening algorithm (ROCA) among women enrolled in the screening arm of this study by occurrence of ovarian, fallopian tube, and peritoneal cancer at completion of accrual to the screening arm after the five year followup
Longitudinal serum, plasma, and tissue repository for biomarker studies and translational research projects by specific studies as sufficient materials are accrued within the repository

Patterns of use of hormonal medications (MHT, SERMs, and bisphosphonates) in surgical and screening arm enrollees by the self-report of medication use at one year after study completion and additional analyses as appropriate
Mortality and incidence of various diseases which complicate long-term estrogen deficiency (e.g., osteoporosis, skeletal fractures, coronary disease, myocardial infarction, and stroke) by self-reported medical history information questionnaire 5 years after study completion
Adherence by study participants to recommendations made regarding the management of non-oncologic morbidity related to premature menopause by annual questionnaire at 2 and 5 years after study completion
Decision-making with reference to cancer risk reduction and screening activities by custom-designed questionnaires administered at the time of study enrollment and at time of cross-over from screening to surgery arms of the study to the first 600 subjects enrolled in the study
Normal ranges and distributions of high-risk women for CA-125 values over time stratified by menopausal status, MHT usage, surgical status, and other risk factors by combining data from 0199 and the CGN ROCA cohorts at conclusion of enrollment into the CGN ROCA cohort (December 2005)
Refine the ROCA algorithm by accounting for defined modifiers of CA-125 level as identified in prior analysis at study completion

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; transvaginal ultrasound (TVUS); and CA 125 measurement. CA 125 is measured every 3 months and the Risk of Ovarian Cancer Algorithm (ROCA) is determined.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; TVUS; and CA 125 measurement. Participants then undergo risk-reducing salpingo-oophorectomy (RRSO). CA 125 is measured and ROCA calculated every 6 months. A mammogram is performed annually. Abnormal screening results are treated as in group I.

Quality of life is assessed at baseline and at 6, 12, 24, and 60 months for some participants.

Participants in group I who decide to undergo RRSO may cross-over to group II at any time.

Greene MH, Piedmonte M, Alberts D, et al.: A prospective study of risk-reducing salpingo-oophorectomy and longitudinal CA-125 screening among women at increased genetic risk of ovarian cancer: design and baseline characteristics: a Gynecologic Oncology Group study. Cancer Epidemiol Biomarkers Prev 17 (3): 594-604, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Gynecologic Oncology Group

Mark Greene, MD, Protocol chair		Ph: 301-594-7642 Email: greenem@mail.nih.gov

Related Information

Featured trial article

Registry Information
Official Title		Prospective Study of Prophylactic Salpingo-Oophorectomy and Longitudinal CA-125 Screening Among Women at Increased Genetic Risk of Ovarian Cancer
Trial Start Date		2003-04-16
Registered in ClinicalTrials.gov		NCT00049049
Date Submitted to PDQ		2002-09-04
Information Last Verified		2006-11-03
NCI Grant/Contract Number		CA27469