Grant Number:	5U01CA271278-02 Interpret this number
Primary Investigator:	Irwin, Melinda
Organization:	Yale University
Project Title:	Trial of Exercise and Lifestyle (TEAL) in Women with Ovarian Cancer
Fiscal Year:	2023

Project Abstract/Summary Ovarian cancer (OC) is the most lethal gynecologic malignancy, with disparities in survival by race and ethnicity. Nearly all stages of OC require aggressive treatment, such that 90% of women diagnosed receive chemotherapy. First-line treatment includes surgery and six cycles of platinum- and taxane-based chemotherapy. Timely and successful completion of chemotherapy is critical, as delayed or reduced chemotherapy dosage for OC is associated with decreased survival; yet chemotherapy dose delays and dose reductions are common. The primary reason for dose delays and reductions is chemotoxicity, including neuropathy, cognitive dysfunction, fatigue, depression, arthralgia, and gastrointestinal toxicities. Muscle loss is an additional consequence of chemotherapy in women with OC. Strategies to manage chemotoxicities include nutrition and exercise. Our team has extensive experience in leading multi-site nutrition and exercise interventions in women with OC and relevant experience with trials specifically addressing chemotherapy completion rates. We will leverage this expertise to address a critical gap: how to reduce chemotoxicity and treatment delays in women with OC. We propose to conduct a multi-site randomized trial of an 18-week medical nutrition therapy and exercise intervention vs. attention control in a racially and ethnically diverse sample of 200 women newly diagnosed with OC (stage I-IV) and initiating curative intent chemotherapy to assess the effect of the intervention on: Aim 1: Relative dose intensity (RDI), an integrated measure of chemotherapy dose delays and reductions; Aim 2: Patient-reported chemotoxicities including neuropathy, cognitive function, depression, fatigue, arthralgia, and gastrointestinal disturbances; Aim 3: Body composition and muscle mass assessed via CT scans and urinary D3‐Creatine dilution method; and Aim 4: Long-term lifestyle behaviors, body composition, patient-reported chemotoxicities, and health care utilization assessed 3- months post-intervention and 12-months post-diagnosis. We hypothesize women randomized to intervention will have higher RDI as compared to women in the attention control arm because of fewer patient-reported chemotoxicities. The intervention will result in attenuated declines in body composition compared with attention control, and women randomized to the intervention will maintain healthy lifestyle behaviors long-term, in turn favorably impacting lingering chemotoxicities and body composition, resulting in less health care utilization compared with attention control. Strengths of our approach is that baseline, follow-up visits and the intervention duration are timed with standard of care in that first-line chemotherapy is completed at ~18 weeks (when our primary endpoint will be assessed) with women undergoing repeat imaging assessments at this timepoint and 3 months later. Positive results would accelerate a paradigm shift with OC patients receiving nutrition and exercise programming as standard of care in tandem with chemotherapy treatment to minimize chemotoxicity and optimize treatment dose delivery for a curative outcome.





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