A Presurgical Window-of-Opportunity Trial of the Effect of Aspirin on Immunological Features of Ovarian Tumors
Abstract
Rationale and Objective of the Proposed Work: Recently, there has been an increasing focus on “repurposing” existing medications with well-known benefits and risks in oncology treatment. Aspirin, a non-steroidal anti-inflammatory drug (or NSAID), is used by nearly 30% of adults in the United States, primarily for cardiovascular disease and colorectal cancer prevention. A recent epidemiologic study conducted by our research team and published in Lancet Oncology observed that women who took aspirin after diagnosis had about a 30% lower risk of death due to ovarian cancer compared to never aspirin users. This, in conjunction, with experimental studies showing that aspirin can improve immune function, reduce inflammation, and lower platelet activation, provides a rationale for the conduct of a randomized trial of aspirin in ovarian cancer patients to examine specific mechanisms by which aspirin might improve survival. The objective of this project is to conduct a randomized-controlled clinical trial in ovarian cancer patients to assess the efficacy and safety of standard-dose aspirin in improving prognosis-related tumor characteristics. The study uses a “window-of opportunity” design, with women starting on aspirin or placebo during neoadjuvant chemotherapy to ensure enough time for aspirin to influence the outcomes of interest. Central Problem Addressed by the Proposed Research: Unfortunately, ovarian cancer is a highly fatal disease, with less than half of patients surviving at least 5 years. Thus, substantial research is focused on improving survival and enhancing quality of life. We propose that adding aspirin in combination with regular chemotherapy may improve a number of factors that are associated with survival or quality of life. Our primary outcome in the trial is the change in the immune cell profiles in the tumor between diagnostic biopsy and interval debulking surgery. Increasing evidence shows that ovarian tumors are characterized by immune suppression, which can prevent the immune system from identifying the tumor as “foreign” and killing the tumor cells. Aspirin can block several pathways that lead to immune suppression and has been shown in studies of ovarian cancer development to change tumor immune profiles. We will secondarily examine other tumor markers that have been associated with poor survival, as well as markers of inflammation and platelet activation. Importantly, in consultation with our patient advocates, we propose to evaluate when women on aspirin compared to placebo pill have fewer physical (fatigue, nausea, peripheral neuropathy, sleep problems) and emotional (depression, anxiety, cognitive function) symptoms during their neoadjuvant chemotherapy. Individuals Who Would Benefit from the Proposed Research: Our goal is to help identify ways to improve ovarian cancer treatment that will extend survival and improve the quality of life in all women with ovarian cancer. Importantly, our study will examine the risk/benefit ratio of aspirin in ovarian cancer patients overall and within certain subgroups. This is because some studies in healthy women suggest that the side effects of aspirin, like gastrointestinal bleeding, may outweigh the benefits in some people, particularly those older than age 70. However, no data exist on this risk-benefit balance in ovarian cancer patients. We want to identify women who could most benefit from aspirin in improving tumor markers related to survival and those who will not have significant negative side effects from including this medication to their treatment plan. Clinical Applications, Benefits, and Risks: The ultimate goal of this development clinical trial is to provide critical data that will inform the conduct of a large-scale randomized, controlled trial of aspirin on ovarian cancer-specific and progression-free survival in patients. This study will provide key biologic and risk-benefit data as well as demonstrate the feasibility and
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010488
Entities
People
- Shelley S. Tworoger
Organizations
- H. Lee Moffitt Cancer Center & Research Institute
- United States Army