Background: Cancer-related cognitive impairment (CRCI) can include persistent memory symptoms, and affects many cancer survivors. Memory and Attention Adaptation Training (MAAT) is an evidence-based cognitive behavioral therapy (CBT) that improves CRCI with demonstrated efficacy in telehealth delivery. MAAT consists of 8 weekly (45-minute) video visits. The aims of this study are to confirm MAAT telehealth efficacy in a phase III RCT (MAAT versus Supportive Therapy; ST) across large catchment areas of two comprehensive cancer centers. A secondary aim is to evaluate treatment-induced brain activation as assessed by functional MRI (fMRI) in a subset of participants. We present remote treatment and data capture methods of this open NCI-sponsored (R01CA244673) randomized clinical trial (NCT 04586530). These methods have high success in participant accrual despite COVID-19 pandemic conditions, and can be readily adopted to other clinical trials to enhance rural/underserved enrollment. Methods: We are enrolling 200 adult, stage I-III breast cancer survivors 1-5 years post-chemotherapy with cognitive complaints. Individuals with CNS disease, previous brain injury, dementia or psychiatric disorder are excluded. All study procedures are completed from the participant’s home (except fMRI). Eligibility screening is a semi-structured phone interview followed by detailed informed consent online (Research Electronic Data Capture: REDCap) with staff phone guidance. Consented participants complete baseline brief phone-based neurocognitive assessment and validated patient-reported outcome measures (PROs) of cognition and quality of life via REDCap. Participants are randomized to MAAT or ST and assigned treating clinicians at respective cancer centers. All 8 visits are completed through secure telehealth platforms, followed by repeat phone/online assessment post-treatment and again at 6 months. Enrollment began in 3/2021. As of 1/2022 (9 months), 56 participants are enrolled (28% of the planned sample), 47 randomized (MAAT 24; ST 23), with 24 completing post-treatment assessments. If all assessments and treatment visits were in person, travel burden per participant is 968 miles/20.5 hours driven, and $542 (US 2021 Federal rate). Thus, study travel savings to date are $30,352. Participant feedback indicates telehealth makes participation possible, similar to previous MAAT research. The current RCT demonstrates utility, efficiency and cost-savings of telehealth and remote data capture technology in the conduct of cancer control research. Elements of methods described can also be adopted for cancer therapeutic trials. Comprehensive cancer centers, where most clinical trials are based, can enhance participation of remote and/or underserved populations that have higher rates of cancer, more disease burden and less opportunity for trial participation. Clinical trial information: NCT04586530.