Abstract OT-38-01: MEDEA: A randomized trial of weight loss to reduce cancer-related fatigue (CRF) among overweight and obese breast cancer (BC) patients
Authors: Di Meglio Antonio , Martin Elise , Michiels Stefan , Charles Cecile , Crane Tracy E. , Barbier Aude , Raynard Bruno , Mangin Anthony , Tredan Olivier , Cottu Paul H. , Vanlemmens Laurence , Segura-Djezzar Carine , Lesur Anne , Pistilli Barbara , Joly Florence , Ginsbourger Thomas , Coquet Bernadette , Jacob Guillemette , Sirven Aude , Bonastre Julia , Ligibel Jennifer A. , Vaz-Luis Ines 
Published: February 2021

Abstract
Rationale: Overweight and obesity are highly prevalent among BC patients and are linked to poorer prognosis and worse patient-reported outcomes (PROs). Weight loss interventions, based on caloric restriction, increased physical activity (PA) and behavioral counselling, are safe and feasible among BC survivors and hold the promise to improve BC-specific outcomes. MEDEA: Motivating to Exercise and Diet, and Educating to healthy behaviors After breast cancer (ClinicalTrials.gov NCT04304924) will evaluate the impact of weight loss on CRF.
Trial design: French multi-center 1:1 randomized controlled trial comparing a 12-month personalized, telephone-based weight loss program + health education intervention vs health education alone in overweight or obese BC patients.
Endpoints and measures: Primary endpoint: difference in self-reported CRF 12 months post-randomization between arms, measured using the EORTC QLQ-C30 CRF subscale. Secondary endpoints: 1) PROs (EORTC QLQ-C30, -B45, -FA12), anxiety and depression (Hospital Anxiety and Depression Scale); 2) weight and body mass index (BMI), diet habits and quality, PA, sleep; 3) cost-effectiveness (number and length of hospital-admissions, all-drug consumption, number and duration of sick leaves). Accelerometer data will be collected to track PA and sleep measures. Qualitative analyses will evaluate patient motivation and satisfaction.
Main eligibility criteria: stage I-II-III BC, primary BC treatment completed within the prior 12 months (definitive surgery, adjuvant chemo-, and/or radio-therapy, if administered), BMI ≥25 kg/m2, ability to walk at least 400 meters at any pace, ECOG PS 0-1, not participating in another weight loss, dietary or PA intervention clinical trial.
Intervention and Control arms: The intervention and health education program are adapted from the BWEL: Breast Cancer WEight Loss study (ClinicalTrials.gov NCT02750826; PI Ligibel JA). The behavior change program is based on the Social Cognitive Theory. Patients in the intervention arm are paired with an individual lifestyle coach, who delivers the intervention through 24 semi-structured telephone calls of 30-60 minutes, supplemented by a detailed participant workbook and scheduled as follows: 1) intensive phase (weeks 1-12), 12 weekly calls; 2) consolidation phase (weeks 13-24), 6 bi-weekly calls; 3) maintenance phase (weeks 25-52), 1 monthly call. Coaches were hired and trained specifically for MEDEA, they are located at a centralized call center and receive support from coordinating nutrition, PA, and behavioral experts. Regular meetings with study team and investigators assure standardized delivery of the intervention and troubleshooting. Intervention goals include weight loss ≥10% of baseline weight, caloric restriction of 500-1000 Kcal/day, increased PA to 150 minutes/week in the initial phase and 225-300 minutes/week in the maintenance phase. Toolbox solutions are offered to tailor the intervention and meet the needs of specific ethnic, socioeconomic or other patient populations with difficulties in achieving intervention goals. All participants in both arms receive a health education program focusing on healthy living.
Accrual: MEDEA will enroll 220 patients overall. Recruitment started in June 2020.
Statistical considerations: The primary analysis of MEDEA will compare the primary endpoint of CRF scores at the 12-month post-randomization time point between arms. The study has 90.0% power at two-sided α=0.05 to detect a standardized effect size of 0.40 (sample size inflated for drop outs). For interpreting the clinical significance of effects, 0.2, 0.5 and 0.8 standard deviation effects will be considered as small, moderate, and large (Cohen, 1988). All other measures, time points and analyses will be considered secondary or exploratory.
Citation Format: Antonio Di Meglio, Elise Martin, Stefan Michiels, Cecile Charles, Tracy E. Crane, Aude Barbier, Bruno Raynard, Anthony Mangin, Olivier Tredan, Paul H. Cottu, Laurence Vanlemmens, Carine Segura-Djezzar, Anne Lesur, Barbara Pistilli, Florence Joly, Thomas Ginsbourger, Bernadette Coquet, Guillemette Jacob, Aude Sirven, Julia Bonastre, Jennifer A. Ligibel, Ines Vaz-Luis. MEDEA: A randomized trial of weight loss to reduce cancer-related fatigue (CRF) among overweight and obese breast cancer (BC) patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-38-01.