Screening for Ovarian Cancer in Older Patients (PLCO Screening Trial)

Study Overview
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Brief Summary
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This clinical trial studies whether screening methods used to diagnose cancer of the prostate, lung, colon, rectum, or ovaries can reduce deaths from these cancers. Screening tests may help doctors find cancer cells early and plan better treatment for ovarian cancer. The ovarian cancer screening tests are part of a trial that addresses the screening of four cancer sites, each with their own results record: prostate (NCT00002540), lung (NCT01696968), colorectal (NCT01696981), and ovarian (NCT01696994).

Detailed Description
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PRIMARY OBJECTIVES: I. To determine whether screening with CA125 and transvaginal ultrasound (TVU) can reduce mortality from ovarian cancer in women aged 55-74 at entry. SECONDARY OBJECTIVES: I. To assess screening variables, other than mortality, for each of the interventions including sensitivity, specificity, and positive predictive value. II. To assess the incidence, stage, and survival of cancer cases. III. To investigate the mortality predictive value of biologic and/or prognostic characterizations of tumor tissue as intermediate endpoints. IV. To conduct biomolecular and genetic research into factors associated with cancer carcinogenesis and promotion, as well as the early detection of these factors. OUTLINE: Participants in the overall PLCO study are stratified by screening center, gender, and age (55-59 vs 60-64 vs 65-69 vs 70-74). Participants are randomized to 1 of 2 arms (control vs screening). ARM I (Control): Participants receive standard medical care. Participants complete a Diet History Questionnaire (DHQ) at baseline. ARM II (Ovarian Screening): Participants undergo blood sample collection for CA125 analysis at baseline annually for 5 years. Serum that is not used in the study will be stored in an NCI biorepository. Participants also undergo an ovarian palpation exam (OVR, discontinued in December 1998) and TVU at baseline and annually for 3 years. A scheduling and tracking procedure is implemented to ensure regular attendance at repeat screens for participants screened negative or for those who are designated suspicious or positive at screening but for whom subsequent diagnostic procedures do not reveal ovarian cancer (follow-up diagnostic procedures are through their own medical care environment). Participants diagnosed with ovarian cancer via a screening test are referred for treatment in accordance with current accepted practice for appropriate stage of disease, patient age, and medical condition; a procedure is provided for contact with qualified medical personnel to insure appropriate therapy. Participants complete a Dietary Questionnaire (DQX) at baseline and DHQ at year 3. An Annual Study Update (ADU) (previously referred to as the Periodic Survey of Health [PSH] questionnaire) is mailed to each participant annually for 13 years to identify all prevalent and incident cancers of the ovaries as all deaths that occur among both screened and control subjects during the trial. After completion of screening, participants are followed up for at least 13 years.

Official Title
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Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial

Conditions
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Ovarian Carcinoma, Ovarian Germ Cell Tumor

Intervention / Treatment
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* Other: Laboratory Biomarker Analysis
* Other: Screening Questionnaire Administration
* Procedure: Ultrasound Imaging


Participation Criteria
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Eligibility Criteria
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Exclusion Criteria: Women who at the time of randomization are less than 55 or greater than or equal to 75 years of age Individuals undergoing treatment for cancer at this time, excluding basal-cell and squamous-cell skin cancer Individuals with known prior cancer of the colon, rectum, lung, or ovary This includes primary or metastatic PLCO cancers Individuals with previous surgical removal of the entire colon or one lung Until October 1996, women with previous surgical removal of both ovaries were excluded from the trial. In order to increase the enrollment of women into the trial, beginning in October 1996, these women were no longer excluded for this reason. Individuals who are participating in another cancer screening or cancer primary prevention trial Prior to April 1, 1999 women were excluded from the trial if they were currently taking or had taken Tamoxifen or Evista\Raloxifene in the past 6 months. As of April 1999 based on a decision from the PLCO Ovary Subcommittee, women who have or are currently taking Tamoxifen or Evista\Raloxifene are not excluded from participation. Individuals who are unwilling or unable to sign the informed consent form Individuals who have had a colonoscopy, sigmoidoscopy, or barium enema in the past three years

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Participants receive standard medical care. Participants complete a DHQ at baseline. | |
| Active Comparator: Ovarian Screening<br>Participants undergo blood sample collection for CA125 analysis at baseline annually for 5 years. Serum that is not used in the study will be stored in an NCI biorepository. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years. Participants complete a DQX at baseline and DHQ at year 3. An ADU (previously referred to as the PSH questionnaire) is mailed to each participant annually for 13 years to identify all prevalent and incident cancers of the ovaries as all deaths that occur among both screened and control subjects during the trial. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Screening Questionnaire Administration<br>* Undergo questionnaire assessments<br>Procedure: Ultrasound Imaging<br>* Undergo TVU<br>* Other names: US;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ovarian Cancer Deaths (Including Primary Peritoneal and Fallopian Tube Cancers) | Ovarian cancer deaths confirmed in participants by a death review committee if available, otherwise by death certificate. | Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years. | 
| Ovarian Cancer Death Rates (Including Primary Peritoneal and Fallopian Tube Cancers) | Ovarian cancer deaths confirmed in participants by a death review committee if available, otherwise by death certificate. Rate is the number of deaths divided by person years of follow-up in the study. | Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Deaths From All Causes | Deaths from all causes were compared between the ovarian cancer screening arm and the usual care arm. | Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years. | 
| Death Rates From All Causes | Deaths from all causes were compared between the ovarian cancer screening arm and the usual care arm. Rate is the number of deaths divided by person years of follow-up in the study. | Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years. | 
| Ovarian Cancer Incidence (Including Primary Peritoneal and Fallopian Tube Cancers) | Ovarian cancer diagnoses confirmed by medical record abstraction. | Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years. | 
| Ovarian Cancer Incidence Rates (Including Primary Peritoneal and Fallopian Tube Cancers). | Ovarian cancer diagnoses confirmed by medical record abstraction. Incidence rate (cumulative) defined as ovarian cancer diagnoses divided by person years at risk for ovarian cancer. | Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years. | 
| Complications of Diagnostic Evaluation (DE) Following a Positive Screening Test | Number of positive screens with complications | One year from screening examination | 
| T0 (Baseline) CA-125 Screening Results | Cancer Antigen 125 (CA-125) result. | T0 (at study entry) | 
| T0 (Baseline) TVU Screening Results | Transvaginal Ultrasound (TVU) result. | T0 (at study entry) | 
| T1 CA-125 Screening Results | Cancer Antigen 125 (CA-125) result. | T1 (one year after entry) | 
| T1 TVU Screening Results | Transvaginal Ultrasound (TVU) result. | T1 (one year after entry) | 
| T2 CA-125 Screening Results | Cancer Antigen 125 (CA-125) result. | T2 (two years after entry) | 
| T2 TVU Screening Results | Transvaginal Ultrasound (TVU) result. | T2 (one year after entry) | 
| T3 CA-125 Screening Results | Cancer Antigen 125 (CA-125) result. | T3 (three years after entry) | 
| T3 TVU Screening Results | Transvaginal Ultrasound (TVU) result. | T3 (three years after entry) | 
| T4 CA-125 Screening Results | Cancer Antigen 125 (CA-125) result. | T4 (four years after entry) | 
| T5 CA-125 Screening Results | Cancer Antigen 125 (CA-125) result. | T5 (five years after entry) |