Abstract Background: Knowledge gained through cancer clinical trials (CTs) has been proven critical to preventing, diagnosing and treating the disease, and providing the evidence base for clinical practice. Major advances in cancer treatment, which are essential for improving patients’ outcomes, come from investigations of new therapeutic agents in CTs. Despite the large number of available studies and improvements in public awareness about CTs, participation of underrepresented minorities in clinical research has been persistently low, with only 2-5% of Latinos and African Americans participating in cancer treatment trials. Barriers to participation are multilevel, complex, and multifactorial, including study design, healthcare system barriers, and patient- and medical team-related factors. Structural inequities, social determinants of health (SDoH), distrust of government, patient-doctor communications, cultural and language barriers, and lower levels of health literacy are barriers for Latino and African American populations. Purpose: To improve informed decision-making about cancer CT participation among cancer patients and community members through a bilingual multilevel, multi-communication approach, including: 1) a 2-group parallel randomized controlled educational trial, and 2) a community awareness campaign. Methods: The randomized study involves 400 patients from the Mays Cancer Center. The intervention group receives 1) a bilingual educational video on CTs with patients’ testimonials, 2) a low literacy booklet, 3) support from a patient navigator (PN), and 4) Salud America! weekly emails with links to online/social media posts on CT. The control group receives a general fact sheet on CTs. Healthcare providers involved in clinical research are invited to participate in Webinars to raise awareness of implicit bias and the importance of inclusive research. The community intervention features a prospective single-group pre/post design, where participants (400) act as their own controls. They receive an educational session on CTs provided by a community health educator + a low literacy booklet. Results: Focus groups guided the development of the video script, booklet, and educational materials. The short video features real cancer patients sharing their experiences with CTs and how they overcame common barriers. Study recruitment began in February 2023. So far, we have recruited 36 cancer patients with a mean age of 51 years, 80% White and 61% Hispanic/Latino, 64% married, 44% had Medicare/Medicaid; 36% < high school education; and 33% earned <$40K. Preliminary results will be presented. Conclusions: Multilevel interventions involving culturally tailored decision aids (i.e., video, booklet) in combination with PN support can effectively address common barriers influencing patient decision-making, raise awareness of CTs, and increase positive attitudes, intentions, and participation in CTs among groups experiencing SDoH. Citation Format: Patricia Chalela, Vivian Cortez, Armida Flores, Sandra Sivak, Edgar Munoz, Cliff Despres, Callie Rainosek, Alyssa Gonzalez, Mio Kitano, Virginia Kaklamani, Kate Lathrop, Sukeshi Arora, Andrew Brenner, Deepak K. Pruthi, Amelie G. Ramirez. My Choices: A multilevel, multicomponent intervention to improve informed decision-making about clinical trial participation among cancer patients [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A064.