Vaccination with dendritic cells pulsed with autologous tumor homogenate in combination with HD-IL2 and immunomodulating radiotherapy in metastatic RCC: a phase II trial Proof of Principle phase II study Study Design Single center, open-label trial to assess response rate Study Duration Total duration: 36 months Enrollment: 24 months Treatment: 5 months per patient Follow-up every three months Primary objectives: Overall Response Rate (ORR) by irRC~Secondary end points:~Toxicity~Overall Survival~Duration of response~PFS~ORR by RECIST 1.1~Prognostic and predictive marker response~Immunological response Study Product, Dose, Route, Regimen and duration of administration Three daily doses boost radiotherapy (XRT) at 6-12 Gy to at least 1, and up to a maximum of 5, metastatic fields, will be administrated on days -4 -3 -2 or -3 -2 -1 before the first and the third cycle of vaccine+IL-2. The first day of administration of vaccine is day +1 and of IL-2 is day +2.~The intradermal autologous dendritic cell vaccine loaded with autologous tumor homogenate plus IL-2 (dose 18 MIU/m2/day in 500cc by continuous IV infusion for 72 hours) will be administered every 3 weeks up to 6 cycles.~Statistical Methodology~This is a Proof of Principle trial with a minimax two stage design:~• Step 1: 12 patients enrolled; A 5% response rate will preclude further study, whereas a 20% response rate will indicate that further study would be warranted.~Using alfa and beta errors of 0.10, if an objective response is observed in at least 1 of the 12 patients enrolled during the first stage the study will go on with a:~• Step 2: recruitment of an additional 25 patients The treatments will be considered active if an objective response is observed in 4 out of 37 patients treated.~The enrolment period will be 24 months. To ensure patients' safety, a continued safety evaluation by an independent DSMB will be performed and formal rules will be planned to continue or stop the recruitment; in particular, the enrollment will be interrupted when six patients completed at least one cycle of the combo treatment and they will be evaluated for safety: if grade ≥3 AEs (except for fever and rash that will be consider only for grade 4) in 2 (two) or more patients will be observed within 30 days after completion of the first dose of combo treatment, the study will be interrupted.
Single center, open-label Proof of Principle phase II trial to assess objective response (ORR).~Three daily doses boost radiotherapy (XRT) at 6-12 Gy to at least 1, and up to a maximum of 5, metastatic fields, will be administrated on days -4 -3 -2 or -3 -2 -1 before the first and the third cycle of vaccine+IL-2. The first day of administration of vaccine is day +1 and of IL-2 is day +2.~Treatment vaccine plus IL-2 (dose 18 MIU/m2/day in 500cc by continuous IV infusion for 72 hours) will be administered every 3 weeks up to 6 cycles.~Total duration of the trial: 36 months~Enrolment period: 24 months~Treatment: maximum of 6 cycles (5 months) per patient~Follow-up every three months until patient died (follow-up until PD and only survival contacts and subsequent therapy for metastatic disease after PD).