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12109 Background: Up to 75% of patients with breast cancer report cognitive decline following chemotherapy. There is no standard of care prevention or treatment of cognitive problems in these patients. This trial (NCT04033419) examines the feasibility of using memantine to prevent cognitive decline during chemotherapy for breast cancer. Methods: We enrolled patients with stage I-III breast cancer scheduled to receive neo/adjuvant chemotherapy. Participants completed a cognitive battery (4 traditional neuropsychological measures and 3 computerized tests) and surveys of self-reported cognition (PROMIS Cognitive Function Short Form 8a) and other neuropsychiatric symptoms at pre-treatment (baseline) and 4 weeks after the last cycle of chemotherapy (post-assessment). Memantine (10 mg BID) was initiated within 1 week of starting chemotherapy and continued until the post-assessment. Adherence and adverse event (AE) monitoring occurred every 2-3 weeks during chemotherapy infusion visits. We used descriptive statistics to evaluate recruitment, retention, and tolerability, adherence, and acceptability of memantine. To evaluate objective cognition, we standardized individual measures using population-based data and averaged them to calculate composite scores of 1) global cognition; 2) attention, working memory, and executive function; and 3) learning and memory. Improvement or decline was defined as ≥ 0.5 SD change between the two assessments. For self-reported cognition, established cutpoints were used to define clinically meaningful change. Results: Of 154 eligible patients approached, 56 (36%) enrolled. Of 51 who completed the baseline assessment and started memantine, 44 (86%) completed the post-assessment; 2 remain active. Among evaluable participants, 92% reported taking ≥ 90% of scheduled doses. Only 36% self-reported cognitive decline, while no change was reported in 57% and improvement in 7%. Decline in objective cognitive domains was observed in 7 - 14% (see Table). There were 7 ≥ grade 3 AEs 2 were possibly related to memantine (diarrhea and hypokalemia). Only 3 participants expressed worry about memantine and only 2 felt that taking memantine disrupted their lives. Conclusions: Our findings suggest that memantine is a safe and feasible intervention for chemotherapy-related cognitive decline and may ameliorate cognitive loss. Randomized controlled trials are needed to determine its preliminary efficacy. Clinical trial information: NCT04033419. [Table: see text]