1. Participating Trials A quality of life assessment of patients participating in phase I clinical trials confirms a decrease during treatment (MC0115) Pamela J. Atherton 1, Daniel W. Szydlo 1, Charles Erlichman 2, Jeff A. Sloan 1 1 Division of Biostatistics, Mayo Clinic, Rochester, MN 2 Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, MN Abstract Background Background: There are psychological challenges associated with participation in Phase I clinical trials due to many consenting patients hoping for a cure despite assertions to dissuade such expectations. This study explored the impact of Phase I trial participation on patient quality of life (QOL). Methods: Patients enrolled onto Phase I studies between 9/10/2002 and 3/6/2007 were asked to complete the Control Preferences Scale (CPS) at baseline, the Linear Analogue Self Assessment (LASA) weekly during cycle 1, and the Trial Satisfaction (TS) survey at the end of cycle 1. All QOL was measured on a 0-10 point scale, 10 being best. The primary endpoint was the change in overall QOL at the end of cycle 1. Summary statistics were calculated for baseline covariates, QOL responses, treatment response and adverse events (AEs). Student’s t-test, Kruskall-Wallis and Pearson/Spearman correlation methodology were utilized. Results: 30 patients from 12 different Phase I trials participated. Overall QOL change from baseline was not significant (mean of -0.5, 95% CI [-0.92, 0.05], p=0.08). Four patients experienced a clinically meaningful deficiency by having an overall QOL decrease of at least 2 points. Significant decreases were seen in Physical Well-Being (WB), Emotional WB, and Mood (p=0.04, 0.04, 0.03, respectively). Correlations comparing QOL with the maximum AE grade were weak, the highest being for Emotional WB and Hopefulness (r=- 0.41, -0.35). Gender and performance status were related to QOL domains of Fatigue, Anxiety and Hopefulness. CPS indicates concordance in preferred compared to played roles. CPS results and treatment response were unrelated to QOL scores. According to TS, patients seemed to feel participation in the treatment trial was worthwhile, they would do it again, and they would recommend the treatment trial to others (means of 8.7, 8.7 and 9.2, respectively), but they did not feel that their QOL improved as a result of the trial (mean of 4.0). Conclusions: Despite being satisfied with their participation in Phase I clinical trials, deficits in QOL appeared, independent of AEs or tumor response. It hence would seem advisable to include assessments in Phase I trials in order to identify and improve patient QOL. Supported in part by CA 69912. Phase I patients have hopes for a cure Phase I trials are not designed to be curative The disparity results in psychological challenges for the patient This study explored the impact of Phase I trial participation on patient quality of life (QOL) Methods Patients enrolled onto Phase I studies between 9/10/2002 and 3/6/2007 were asked to complete: the Control Preferences Scale (CPS) at baseline the Linear Analogue Self Assessment (LASA) weekly during cycle 1 the Trial Satisfaction (TS) survey at the end of cycle 1 All QOL was measured on a 0-10 point scale, 10 being best. The primary endpoint was the change in overall QOL at the end of cycle 1. Summary statistics were calculated for baseline covariates, QOL responses, treatment response and adverse events (AEs). Student’s t-test, Kruskall-Wallis and Pearson/Spearman correlation methodology were utilized. Linear Analogue Self Assessment Control Preferences Scale Pain Frequency was the only QOL domain that improved. Results Conclusion Despite being satisfied with their participation in Phase I clinical trials, deficits in QOL appeared independently of AEs or tumor response. It hence would seem advisable to include assessments in Phase I trials in order to identify and improve patient QOL. Contact Information: atherton@mayo.edu (Degner L, Sloan JA, Venkatesh P. The control preferences scale. Canadian Journal of Nursing Research 29:21-43, 1997.) 1.Circle the letter next to the phrase below that best describes the role you have actually been playing in dealing with your cancer diagnosis. The Control Preferences Scale Active RolePassive Role A. I prefer to make the decision about which treatment I will receive. E. I prefer to leave all decisions regarding my treatment to my doctor. B. I prefer to make the final decision about my treatment after seriously considering my doctor’s opinion. D. I prefer that my doctor makes the final decision about which treatment will be used, but seriously consider my options. Collaborative Role C. I prefer that my doctor and I share responsibility for deciding which treatment is best for me. Patients had high trial satisfaction in spite of little QOL improvement. Overall QOL decreased independent of select demographics. AE grade did not affect patient determination of whether it was worthwhile participating in the clinical trial. Also asked other questions regarding overall emotional well being, social activity, spiritual well being, level of hopefulness, average fatigue, level of anxiety, mood and level of social support. Also asked which role the patient would have preferred. Trial Satisfaction Survey Directions: Please circle the number (0-10) best reflecting your response to the following statements: 1. It was worthwhile to go on this clinical trial. 012345678910 Not worthwhile at allVery Worthwhile 2. Your quality of life has improved on this trial. 012345678910 No improvement at allVery much improved 3. If you had to do it over, would you participate in this trial again. 012345678910 Would never participateWould definitely participate 4. You would recommend going on this trial to others. 012345678910 Would never recommendWould definitely recommend Patient Demographics (N=30) Comparison of QOL score means and tumor response indicated no differences between best treatment responses (1 Partial Response, 15 Stable Disease, 12 Progressive Disease). Correlation of QOL scores with Treatment Satisfaction yielded moderate associations at best. The largest correlation occurred when comparing the decrease in pain frequency to the worthwhileness of participating on a clinical trial (Pearson r=0.66). There were no differences in changes in baseline in any QOL scores as compared between patients rating the parent trial as worthwhile (as indicated by a score of 5 or higher in the Trial Satisfaction Survey) vs those who did not. Change from Baseline of LASA Scores Summary of Trial Satisfaction Change from Baseline of Overall QOL Trial Satisfaction with Maximum Severity of AEs Other Results *All patients reported that they were actually playing the role they preferred. No trial enrolled more than 5 patients. ProtocolAgent(s)ProtocolAgent(s) MC0012 PS-341 Paclitaxel Carboplatin MC0014 Flavopiridol 5-FU/Leucovorin CPT-11 MC0111 17-AAG Gemcitabine Cisplatin MC0116 CPT-11 Taxotere Celecoxib MC0112 CPT-11 OSI-774 MC0511 BAY 43-9006 PS-341 MC0622ATM99010217-AAG C0137-34 EKB-539 Capecitabine CA158-011 BMS-214662 Paclitaxel Carboplatin 100647 Geftinib BAY 43-9006 D20001APC8024 Total Age Performance Status N30 013 (43.3%) Mean (SD)54.5 (13.0) 116 (53.3%) Median55.0 21 (3.3%) Range(30.0-78.0) Gender Type of Disease Male14 (46.7%) Missing11 (37%) Female16 (53.3%) Solid tumor19 (63%) Race CPS (Played/Preferred)* White20 (66.7%) Active/Active10 (39%) Black or African American1 (3.3%) Collaborative/Collaborative12 (52%) Not reported9 (30%) Passive/Passive2 (9%) Cycles of Treatment (3 missing)Route of Treatment 0-15 (18.5%) Oral3 (10%) 2-313 (48.1%) IV bolus4 (13.3%) 4-54 (14.8%) IV continuous infusion8 (26.7%) 6+5 (18.5%) A combination of routes 15 (50%) Treatment Setting Outpatient24 (80%) Inpatient6 (20%) Was the study worthwhile? Grade Total 1234 No 12205 Yes 267318 P-value = 0.77