NCT03226236

Vaccination With Dendritic Cells Pulsed With Autologous Tumor Homogenate in Combination With HD-IL2 and Immunomodulating Radiotherapy in Metastatic RCC

Vaccination With Dendritic Cells Pulsed With Autologous Tumor Homogenate in Combination With HD-IL2 and Immunomodulating Radiotherapy in Metastatic RCC: a Phase II Trial (RENALVax-2)

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS · Academic / Other
• Sex: All
• Age: 19 Years
• Healthy volunteers: Not accepted

Summary

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).

Detailed description

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: 1. Toxicity 2. Overall Survival 3. Duration of response 4. PFS 5. ORR by RECIST 1.1 6. Prognostic and predictive marker response 7. 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.

Conditions

• Carcinoma, Renal Cell
• Vaccination
• Secondary

Interventions

Type	Name	Description
RADIATION	boost radiotherapy (XRT)	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
BIOLOGICAL	Autologous DC vaccine	The first dose (7 to 14 x 10\_6 total dendritic cells) will be performed with freshly prepared vaccine, 9 days after leukapheresis; on day +1 starting from cycle 2 (3 weeks after the first cycle, on completion of QA assessments on the cryopreserved products), 5 additional doses will be administered every 3 weeks until maximum six vaccines.
DRUG	High-Dose IL-2	high dose IL-2: 18 MIU/m2/day in 500cc administered by continuous IV infusion for 72 hours starting day +2.

Timeline

• Start date: 2016-03-01
• Primary completion: 2019-03-01
• Completion: 2019-03-01
• First posted: 2017-07-21
• Last updated: 2018-11-13

Locations

1 site across 1 country: Italy