Clinical Predictors of Early Trial Discontinuation for Patients Participating in Phase I Clinical Trials in Oncology

SIMPLE SUMMARY: About 20% of patients with cancer who participate in a phase I clinical trial discontinue the trial early. Early trial discontinuation is undesirable both for the wellbeing of the patient as well as for the trial efficiency and the development of new anticancer drugs. We investigated which clinical predictors at baseline were significantly associated with early trial discontinuation of patients with cancer who participated in phase I clinical trials. The clinical predictors which were identified in this study were hyponatremia, elevated alkaline phosphatase level, performance score of 1 or higher and opioid use. Hyponatremia especially, which was the strongest predictor, should be considered to be used as an additional eligibility criterion in order to reduce the early trial discontinuation of patients with cancer who participate in phase I clinical trials. ABSTRACT: Despite stringent eligibility criteria for trial participation, early discontinuation often occurs in phase I trials. To better identify patients unlikely to benefit from phase I trials, we investigated predictors for early trial discontinuation. Data from 415 patients with solid tumors who participated in 66 trials were pooled for the current analysis. Early trial discontinuation was defined as (i) trial discontinuation within 28 days after start of treatment or (ii) discontinuation before administration of the first dosage in eligible patients. Multilevel logistic regression analyses were conducted to identify predictors for early trial discontinuation. Eighty-two participants (20%) demonstrated early trial discontinuation. Baseline sodium level below the lower limit of normal (OR = 2.95, 95%CI = 1.27–6.84), elevated alkaline phosphatase level > 2.5 times the upper limit of normal (OR = 2.72, 95%CI = 1.49–4.99), performance score ≥ 1 (OR = 2.07, 95%CI = 1.03–4.19) and opioid use (OR = 1.82, 95%CI = 1.07–3.08) were independent predictors for early trial discontinuation. Almost 50% of the patients with hyponatremia and all four patients in whom all four predictors were present together discontinued the trial early. Hyponatremia, elevated alkaline phosphatase level, performance score ≥ 1 and opioid use were identified as significant predictors for early trial discontinuation. Hyponatremia was the strongest predictor and deserves consideration for inclusion in eligibility criteria for future trials.