e18579 Background: Clinical trials (CTs) are essential for advancing care for individuals with cancer, yet a minority of patients participate in CTs. We conducted an exploratory analysis of CT perceptions (knowledge, attitudes, and barriers) among patients with GI cancer. Methods: We prospectively surveyed a convenience sample of patients treated for GI cancer at Massachusetts General Hospital from 11/2020–12/2021. We obtained sociodemographic/clinical characteristics via patient report and chart review. We assessed CT perceptions, communication confidence (Perceived Efficacy in Patient-Physician Interactions Questionnaire, PEPPI, range 0-50; higher score indicates higher confidence), and illness perceptions (Brief Illness Perceptions Questionnaire, BIPQ, range 0-80; higher score indicates more negative perceptions). Using descriptive statistics, we examined associations of CT perceptions with patient characteristics, communication confidence, and illness perceptions. Results: We enrolled 80 patients (median age = 66 years [range 24-85], 54% men, 93% white, 48% had metastatic disease, 69% had college/postgraduate degrees, 15% had participated in CTs [25% phase I, 75% phase II-III]). Cancer types were pancreatic (38%), colorectal/bowel (23%), hepatobiliary (18%), gastroesophageal (16%), and other (6%). Median PEPPI was 43 (range 16-50). Median BIPQ was 44 (range 1-66); 63% reported negative illness perceptions (BIPQ≥40). Most (89%) agreed CTs are essential to improving standard treatment, yet only 42% had discussed CTs during care. Overall, 38% reported a clear idea of what a CT means, and 8% thought most people are cured on CTs. Unmarried patients were more likely to think most people are cured on CTs (21% vs 4%, p = .017). Most (76%) saw CTs as opportunities to obtain new treatment; only 15% believed enrolling would mean missing out on standard care. Only 16% thought most patients like them enroll in CTs. Younger patients (≤65 years) were more likely to think most patients like them enroll (25% vs 8%, p = .046). Most (61%) felt confident differentiating a CT from other treatments. Older patients (> 65 years) were more likely than younger patients to agree/strongly agree that they feel confident differentiating a CT from other treatments (74% vs 49%, p = .025), as were men versus women (76% vs 43%, p = .003). Those with higher communication confidence (Medians [M]: 44 vs 40, p = .04) or more positive illness perceptions (M: 41 vs 50, p = .003) were also more likely to be confident differentiating a CT. Conclusions: In this exploratory analysis of CT perceptions among patients with GI cancer, we found high levels of CT knowledge and positive CT perceptions. We demonstrated hypothesis-generating associations among patient factors and CT perceptions, underscoring the need for future research to confirm our findings and to develop interventions to enhance CT decision-making and participation.