Risk-guided cardioprotection with carvedilol in patients with breast cancer (CCT guide): a phase 1 randomized clinical trial.

Purpose: Breast cancer treatment results in increased cardiotoxicity risk; a risk-guided approach to cardioprotection has not been fully tested.

Methods: This single-center, randomized Phase I trial enrolled patients with Stage I-III breast cancer who planned to receive anthracycline and/or trastuzumab therapy. An internally validated cardiotoxicity risk score classified participants as low or elevated risk. Elevated risk participants were randomized to receive open-label carvedilol or usual care for 12 months, beginning at cancer therapy initiation. Study visits occurred at baseline, 3, 6, 9, 12, and 24 months. Primary outcomes included feasibility, safety, and tolerability. Exploratory outcomes included echocardiography, biologic, and patient-reported measures.

Results: Of the 166 eligible patients approached, 68 (41%) agreed to participate and ultimately enrolled. Among these participants (median age 52, 35% Black), 49 were classified as low and 19 elevated risk. Within the elevated risk group, 13 were randomized to carvedilol and 6 usual care. For those randomized to carvedilol, the median maximum dose was 6.25 mg twice daily, with 93% adherence. Adverse events of interest (grade 3 + bradycardia, hypotension, or fatigue) occurred in 9% with carvedilol, 13% in usual care, and 4% in low risk groups. One (1.5%) low risk participant experienced cardiac dysfunction. There were no substantial differences in secondary outcomes across groups. The participant withdrawal rate was 7%.

Conclusions: This Phase 1 trial demonstrates that a risk-guided strategy can be applied to patients with active cancer. However, additional strategies are necessary to optimize the design and execution of non-treatment intervention trials in patients with active cancer.

Trial registration: NCT04023110.