8.4.9 Exploratory AnalysesNone planned.9 COLLABORATIVE AGREEMENTSNone. Abbreviated Title: Personalized DC Vaccine Version Date: March 26, 2018 3910 HUMAN SUBJECTS PROTECTIONS RATIONALE FOR PATIENT SELECTION Subjects from both genders and all racial/ethnic groups are eligible for this study if they meet the eligibility criteria. To date, t here is no information that sugg ests that differences in drug metabolism or disease respons e would be expected in one group compared to another. Efforts will be made to extend accrual to a representative population, but in this preliminary study, a balance must be struck between pa tient safety considerations an d limitations on the number of individuals exposed to potentiall y toxic and/or ineffective tre atments on the one hand and the need to explore gender and ethnic aspects of clinical research on the other hand. If differences in outcome that correlate to gender or to ethnic identity are noted, accrual may be expanded or a follow-up study may be written to investigate those differences more fully. We will limit enrollment to patients 70 years of age or less bec ause based on our admittedly limited experience with prior AC T clinical trials, younger patie nts tolerate and recover from these toxicities better than elderly patients. PARTICIPATION OF CHILDREN Since the efficacy of this ex perimental procedure is unknown, it does not seem reasonable to expose children to this risk wit hout further evidence of benefi t. Should results of this study indicate efficacy in t reating metastatic cancer, which is not r esponsive to other standard forms of therapy, future research can be conducted in the pediatric popul ation to evaluate potential benefit in that patient population. PARTICIPATION OF SUBJECTS UNABLE TO GIVE CONSENT Adults unable to give consent are excluded from enrolling in th e protocol. However, re-consent may be necessary and there is a possibility, though unlikely, t hat subjects could become decisionally impaired. For this reason and because there is a p rospect of direct benefit from research particip ation (Section 10.5 DOOVXEMHFWVDJHZLOOEH RIIHUHGWKHRSSRUWXQLW\WRILO O in their wishes for research and care, and assign a substitute decision maker on the “NIH Advance Directive for Health C are and Medical Research Particip ation” form so that another person can make decisions about th eir medical care in the event that they become incapacitated or cognitively impaired during the course of the study. Note: T he PI or AI will contact the NIH Ability to Consent Assessment Team for evaluation. For those sub jects that become incapacitated and do not have pre-de termined substitute decisio n maker, the procedures described in MAS Policy 87-4 for a ppointing a surrogate decision maker for adult subjects who are (a) decisionally impaire d, and (b) who do not have a legal guardian or durable power of attorney, will be followed. EVALUATION OF BENEFITS AND RISKS/DISCOMFORTS The experimental treatment has a chance to provide clinical ben efit though this is unknown. The NCI SB has extensive experience w ith ACT following treatment wit h high-dose aldesleukin, however this experimental treatme nt does not incl ude the standar d NCI SB preparative regimen or high-dose aldesleukin. Alt hough we have seen responses to prior NCI SB ACT treatments, we do not know if this change in our pr ocess will imp rove patient outcome. The risks associated with ACT are substantial, including, a delay in treatment due t o the need to harvest and grow the cells, a surgical procedure (pos sible major) to obtain tumor fo r the cell product, the possibility Abbreviated Title: Personalized DC Vaccine Version Date: March 26, 2018 40that a cell product cannot be ge nerated, infection due to the s urgical procedure, and death. The risks in this treatment are detailed in Section 11.