Clinical Trial to Screen Participants Who Are at High Genetic Risk for Ovarian Cancer

NCT ID: NCT00039559

Last Updated: 2013-06-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 2430 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-05-31
• Study Completion Date: 2014-12-31

Brief Summary

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 cancer antigen 125 (CA125) levels in detecting ovarian cancer in participants who have a high genetic risk of developing ovarian cancer.

Detailed Description

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 CA125 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 breast cancer susceptibility gene (BRCA) mutation criteria or family history criteria undergo a probability of having a BRCA mutation given family history of cancer (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 6 months-7 years. Participants undergo blood draws for measurement of CA125 levels once every 3 months for 6 months-7 years. For each CA125 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 CA125 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 CA125 level prior to TVS. Participants with normal TVS continue CA125 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 CA125 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 CA125 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 CA125 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 CA125 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 CA125 screening as above. Participants who are referred for standard clinical intervention and are not found to have malignancy continue CA125 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.

Conditions

Ovarian Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SCREENING
• Blinding Strategy: NONE

Study Groups

Early detection

Group Type: OTHER

Early detection

Intervention Type: OTHER

CA125 is measured in blood and the longitudinal results interpreted with a statistical algorithm to determine if there has been a significant increase from baseline.

Interventions

Early detection

CA125 is measured in blood and the longitudinal results interpreted with a statistical algorithm to determine if there has been a significant increase from baseline.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 30 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Steven Skates

Steven Skates PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Steven J. Skates, PhD

Role: STUDY_CHAIR

Massachusetts General Hospital

Locations

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, United States

Countries

United States

Other Identifiers

MGH-000084

Identifier Type: -

Identifier Source: secondary_id

CDR0000069397

Identifier Type: -

Identifier Source: org_study_id

NCT00301743

Identifier Type: -

Identifier Source: nct_alias