Randomized trial of REVITALIZE: A telehealth intervention to reduce fatigue interference among adults with advanced ovarian cancer on PARP inhibitors

In the era of precision oncology, more patients are living longer with advanced cancer, yet many of the new strategies require years of fatiguing treatment. While cognitive behavioral therapy (CBT) is an effective treatment for fatigue in early-stage cancer, for advanced cancer a recent Cochrane meta-analysis found few trials and “very low-quality evidence” for its enduring benefit on fatigue at follow-up. It is also unknown if addressing fatigue improves adherence to cancer treatment. Finally, given that advanced cancer typically requires ongoing treatment, it is more realistic to reduce the negative interference of fatigue with quality of life (“fatigue interference”) than to eliminate fatigue itself. Thus, fully powered trials of promising interventions for fatigue interference are critically needed to improve outcomes in advanced cancer survivors. Ovarian cancer represents an ideal context to test such interventions as most patients are diagnosed with advanced disease and, after initial treatment, are prescribed oral poly ADP-ribose polymerase (PARP) inhibitors for 2-3 years. PARP inhibitors, which are increasingly used to treat other cancers, cause life-interfering fatigue in nearly half of patients (relative to placebo). To address these limitations, we developed, refined, and piloted REVITALIZE – a telehealth intervention to address fatigue interference among patients with advanced ovarian cancer taking PARP inhibitors. Based on Acceptance and Commitment Therapy (ACT), a CBT variant well-matched to the context of advanced cancer, REVITALIZE has patients identify and reduce contributors to fatigue beyond PARP inhibitors, clarify and align their behavior with their values, and use active acceptance strategies to reduce fatigue interference in daily life. In a pilot randomized trial (N=44), relative to enhanced usual care (EUC), REVITALIZE reduced fatigue interference at 12-week follow-up, p=.008, by a large effect; improved fatigue severity, selfefficacy, and catastrophizing, and quality of life; and led to fewer dose delays and reductions. We propose to conduct a fully-powered, randomized controlled trial that includes adherence outcomes and longer follow-up across both community and academic cancer clinics that serve diverse communities, comparing REVITALIZE to EUC (N=240) assessed at baseline, mid-intervention (to assess mechanisms), post-intervention, and 4- and 6month follow-up. Aims are (1) To evaluate REVITALIZE vs. EUC effects on fatigue interference (primary outcome), fatigue severity, self-efficacy, and catastrophizing, and quality of life (secondary outcomes); (2) To assess the effect of REVITALIZE vs. EUC on objective PARP inhibitor monthly adherence, dose interruptions and reductions, and persistence using Wisepill medication monitoring devices and chart review; (3) To assess the theory-driven mechanisms of REVITALIZE–active acceptance and alignment of behavior with values–by examining mediators of REVITALIZE effects compared to EUC. If efficacious, REVITALIZE will provide a scalable telehealth intervention to improve survivorship in advanced ovarian cancer, that can be readily adapted to address fatigue among the growing community of advanced cancer survivors.