Early Supportive Versus Standard Care in Phase I Cancer Trials: A Randomized Controlled Trial.

Abstract

Patients enrolled in Phase I clinical trials often face substantial physical and psychological challenges. Although supportive and palliative care interventions have been previously investigated in cancer, evidence regarding their early and structured integration in Phase I populations remains limited. Multidisciplinary supportive approaches may improve symptom control and patient-centered outcomes in this context. To evaluate the impact of a structured early supportive care (ESC) program on overall quality of life, encompassing physical, psychological, and social dimensions, in patients participating in Phase I clinical trials, delivered through a systematic referral process to psycho-oncology, hospital social work, and palliative care. Participants were randomized 1:1 to receive either standard care (SC) or ESC program. The primary outcome was symptom burden, assessed with the Edmonton symptom assessment system (ESAS) which served as a proxy for overall quality of life. Secondary endpoints included psychosocial needs, assessed with the evaluation of psychosocial needs in palliative care (ENP-E) and ad hoc items on sociofamilial needs. The intervention involved multidisciplinary case discussions and referrals to appropriate supportive care services. Data were collected at baseline and at three monthly follow-ups. Longitudinal continuous outcomes were analyzed using linear mixed-effects models, and sociofamilial outcomes were analyzed using generalized estimating equations with a binomial distribution and logit link. A total of 186 patients were randomized. ESC participants improved over time, whereas SC participants worsened in both symptom burden and psychosocial needs. Linear mixed-effects models showed significantly lower ESAS scores in the ESC group (group effect β = -14.44, 95% confidence interval [95% CI] -18.13 to -10.75), with significant group × time interactions indicating attenuation of the between-group difference over time (ESC × T1: β = -14.50, 95% CI -19.21 to -9.78; ESC × T2: β = -6.75, 95% CI -10.67 to -2.83). Similar patterns were observed for psychosocial needs assessed with ENP-E (group effect: β = -3.38, 95% CI -4.52 to -2.24; ESC × T1: β = -3.61, 95% CI -5.08 to -2.14; ESC × T2: β = -1.87, 95% CI -3.14 to -0.61). Improvements in sociofamilial needs were limited to distance-related and guidance-related items. At baseline, 54% of ESC participants accessed palliative medicine, with 27% referred to psycho-oncology and social work. By T3, referrals declined to 39%, 21%, and 13%. Early integration of supportive care significantly improves symptom control and psychosocial well-being in patients enrolled in early-phase cancer trials. These findings highlight the value of early, structured multidisciplinary supportive care models specifically tailored to the needs and clinical context of Phase I cancer research.