Quality-of-Life (QOL) during Screening for Phase 1 Trial Studies in Patients with Advanced Solid Tumors and Its Impact on Risk for Serious Adverse Events.

Sidra Anwar,Grace K Dy,Austin Miller,Dawn Depaolo,Chi-Chen Hong,Amy Whitworth,Ann Marie Diraddo,Askia Dozier,Wen Wee Ma,Wei Tan,Sonal Admane,Alex A Adjei,Sandra M Jacob,Francine Siedlecki

doi:10.3390/cancers9070073

Abstract

Background: Serious adverse events (SAEs) and subject replacements occur frequently in phase 1 oncology clinical trials. Whether baseline quality-of-life (QOL) or social support can predict risk for SAEs or subject replacement among these patients is not known. Methods: Between 2011–2013, 92 patients undergoing screening for enrollment into one of 22 phase 1 solid tumor clinical trials at Roswell Park Cancer Institute were included in this study. QOL Questionnaires (EORTC QLQ-C30 and FACT-G), Medical Outcomes Study Social Support Survey (MOSSSS), Charlson comorbidity scores (CCS) and Royal Marsden scores (RMS) were obtained at baseline. Frequency of dose limiting toxicities (DLTs), subject replacement and SAEs that occurred within the first 4 cycles of treatment were recorded. Fisher’s exact test and Mann-Whitney-Wilcoxon test were used to study the association between categorical and continuous variables, respectively. A linear transformation was used to standardize QOL scores. p-value ≤ 0.05 was considered statistically significant. Results: Baseline QOL, MOSSSS, CCS and RMS were not associated with subject replacement nor DLTs. Baseline EORTC QLQ-C30 scores were significantly lower among patients who encountered SAEs within the first 4 cycles (p = 0.04). Conclusions: Lower (worse) EORTC QLQ-C30 score at baseline is associated with SAE occurrence during phase 1 oncology trials.

Highlights

Phase 1 oncology trials are mainly designed to evaluate the toxicity and pharmacokinetic profiles of investigational agents in order to determine the appropriate dose for subsequent phase 2 testing.Phase 1 trial participants typically have advanced cancer for which standard therapies are either not available or have been exhausted
A total of 104 patients consented to this study. 92 patients had lactate dehydrogenase (LDH) level drawn at baseline for Royal Marsden scores (RMS) calculation
There was no significant difference in baseline QOL scores according to RMS across the different QOL questionnaires (Table 3)

Summary

Introduction

Phase 1 oncology trials are mainly designed to evaluate the toxicity and pharmacokinetic profiles of investigational agents in order to determine the appropriate dose for subsequent phase 2 testing.Phase 1 trial participants typically have advanced cancer for which standard therapies are either not available or have been exhausted. While patient performance status and organ function data are routinely used to determine eligibility for phase 1 study involvement, a recent retrospective review showed a 50% SAE rate in cycle 1 among patients participating in phase 2 trials of molecularly-targeted agents [7]. This demonstrates a gap in our current process for optimizing patient selection to minimize non-treatment related AEs. Serious adverse events (SAEs) and subject replacements occur frequently in phase 1 oncology clinical trials.

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Discussion

Conclusion