We propose to conduct a randomized controlled trial (RCT) to compare safety, feasibility and positive predictive value (PPV) of two ovarian cancer screening strategies, one using CA125 and HE4 together as a first-line screen, the other introducing HE4 as a second-line screen. Women aged 35-80 will be eligible if they are at elevated risk based on a documented mutation in BRCA1 or BRCA2 or a pedigree suggestive of inherited susceptibility;800 such women will be enrolled and screened semi-annually. Women aged 50-80 will be eligible if they have elevated risk based on a previously developed OvCaRisk model;400 such women will be enrolled and screened annually. We will interpret serum markers using the previously developed parametric empirical Bayes (PEB) longitudinal algorithm (above a threshold corresponding to 90%, 95% or 99% specificity) to take advantage of rise in a marker as a signal of disease, a phenomenon that has been well documented. We will target a positive predictive value of 10% in both arms, corresponding to a ratio of 10 surgeries per cancer detected.
In Aim 1 we will document protocol-indicated surgical procedures and malignancies detected in order to rule out a ratio of surgeries to malignancies greater than 20.
In Aim 2 we will document compliance with first- and second-line screens and test the null hypothesis that compliance does not differ between the two arms.
In Aim 3 we will document effects on health-related quality of life (HRQOL) and test the null hypotheses that 1) effects on HRQOL do not differ between the two arms and 2) effects on cancer worry do not differ between women who do and do not experience a false-positive first-line screen. Our goal is that the results of this RCT together with results of ongoing large efficacy trials will lead to clinical implementation of screening using novel markers within 5 years. We have partnered with Abbott Diagnostics and the Canary Foundation to accelerate translation. Four clinical centers (Swedish Medical Cancer, Cedars-Sinai, Stanford and City of Hope) will participate, and participation will be offered to all Ovarian SPORE institutions. Data will also support analyses ofthe cost- effectiveness of screening using each strategy, and estimation of the costs of conducting a full-scale efficacy trial should such a trial be required in the future.

Public Health Relevance

This project will introduce HE4 as an early detection and diagnostic marker for the first time in a prospective clinical trial. We will denhonstrate and evaluate better strategies than are currently used for screening high- risk women. Clinical implementation may follow without the need for another large trial, by combining data from this study with reports from ongoing efficacy trials.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA083636-15
Application #
8523015
Study Section
Special Emphasis Panel (ZCA1-RPRB-M)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
15
Fiscal Year
2013
Total Cost
$138,833
Indirect Cost
$41,441
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
Stephan, Sirkka B; Taber, Alexandria M; Jileaeva, Ilona et al. (2015) Biopolymer implants enhance the efficacy of adoptive T-cell therapy. Nat Biotechnol 33:97-101
Karlan, Beth Y; Thorpe, Jason; Watabayashi, Kate et al. (2014) Use of CA125 and HE4 serum markers to predict ovarian cancer in elevated-risk women. Cancer Epidemiol Biomarkers Prev 23:1383-93
Cecil, Denise L; Holt, Gregory E; Park, Kyong Hwa et al. (2014) Elimination of IL-10-inducing T-helper epitopes from an IGFBP-2 vaccine ensures potent antitumor activity. Cancer Res 74:2710-8
Palanca-Wessels, Maria Corinna; Press, Oliver W (2014) Advances in the treatment of hematologic malignancies using immunoconjugates. Blood 123:2293-301
Miller, Chris P; Thorpe, Jason D; Kortum, Amanda N et al. (2014) JAK2 expression is associated with tumor-infiltrating lymphocytes and improved breast cancer outcomes: implications for evaluating JAK2 inhibitors. Cancer Immunol Res 2:301-6
Topp, Monique D; Hartley, Lynne; Cook, Michele et al. (2014) Molecular correlates of platinum response in human high-grade serous ovarian cancer patient-derived xenografts. Mol Oncol 8:656-68
Pennington, Kathryn P; Walsh, Tom; Harrell, Maria I et al. (2014) Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas. Clin Cancer Res 20:764-75
Cheon, Dong-Joo; Orsulic, Sandra (2014) Ten-gene biomarker panel: a new hope for ovarian cancer? Biomark Med 8:523-6
Duggan, Catherine; Wang, Ching-Yun; Xiao, Liren et al. (2014) Aspirin and serum estrogens in postmenopausal women: a randomized controlled clinical trial. Cancer Prev Res (Phila) 7:906-12
Emori, Megan M; Drapkin, Ronny (2014) The hormonal composition of follicular fluid and its implications for ovarian cancer pathogenesis. Reprod Biol Endocrinol 12:60

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