Background: SD have been described as a significant symptom burden for cancer patients and their caregivers. However, in advanced cancer, the prevalence of SD and its impact on the quality of life (QOL) and psychological morbidity of ACP over time has not been described. Methods: A prospective cohort of ACP participating in phase I trials was assessed at baseline (T1) and one month (T2) using psychosocial instruments: cognition (MMSE); depression(CES-D), state anxiety (STAI-S), QOL(FACIT-Pal), global health (SF-36). Semi-structured interviews evaluated SD patterns including: quality/latency, habitual efficiency, daytime dysfunction. Results: To date,152 subjects (76 ACP and 76 CG) have been separately interviewed at T1 and T2. For the total population: median age 61 (28-78y); 51% male; 100% married; 90% Ca; 64% > HS educ; 52% GI dx; 51% income < $65,000 yr; ACP median survival 7.9 months (0.41-18.2). At T1, 57% of ACP reported experiencing SD within the past week including: 55.6% insomnia, 44% nonrestorative sleep, 49% low energy, 48% daytime somnolence. For CG, 72% reported experiencing SD: 68% insomnia, 64% nonrestorative sleep, 69% fatigue, 66% daytime somnolence. At T2, rates remained consistent over time for both ACP and CG across time with the exception of increased insomnia at 61% and 76% respectively. After controlling for pain, mood, and fatigue, ACP with self-reported SD had higher STAI-S (33 ±11 v 29 ±8 , p = 0.02) and poor global health (54 ± 19 v. 64 ± 21, p = 0.01) at T2. CG with SD had higher STAI-S anxiety (39 ± 17 v 35 ± 13, p = 0.03) and poor global health (75 ±26 v 88±16, p = .0002) at T2.Regression analyses revealed ACP with self-reported insomnia had poorer FACIT-Pal QOL (59 ± 9 v 63 ± 10, p = 0.01) over time. Prior chemotherapy was associated with ACP SD (70% v. 33%, p = 0.02). Regarding prognosis, ACP with insomnia had shorter median survival (5.5 v. 7.2 months, p = 0.01). Conclusions: SD are prevalent among ACP participating in clinical trials and were associated with disease progression, QOL, and anxiety. Multidisciplinary supportive care interventions designed to address SD are warranted.