Nivolumab Plus Stereotactic Body Radiotherapy in II and III Line of Patients With Metastatic Renal Cell Carcinoma

Browse trials for

• Carcinoma, Renal Cell 1,960
• Kidney Neoplasms 954

Study arms

• Experimental
  Nivolumab

  Hypofractionated radiation will be administered to a metastatic disease site at a dose and schedule of 30 Gy in 3 consecutive fractions. The day of first administration of Nivolumab will be designated as Time 1. Nivolumab will be given as flat dose of 240 mg in intravenous infusion beginning on day 1 every 14 days for 6 months, than switch to 480 mg q4-weekly in responding (CR, PR, SD) patients until PD or unacceptable toxicity . SRT will be administered between the first and second administration of Nivolumab (7 days after the first infusion of Nivolumab).

  Drug: Nivolumab

Interventions

• DrugNivolumab

  Hypofractionated radiation will be administered to a metastatic disease site at a dose and schedule of 30 Gy in 3 consecutive fractions. The day of first administration of Nivolumab will be designated as Time 1. Nivolumab will be given as flat dose of 240 mg in intravenous infusion beginning on day 1 every 14 days for 6 months, than switch to 480 mg q4-weekly in responding (CR, PR, SD) patients until PD or unacceptable toxicity . SRT will be administered between the first and second administration of Nivolumab (7 days after the first infusion of Nivolumab).

Primary outcomes

1. ORR Objective Response Rate

   Objective Response Rate (ORR) , as determined by investigator assessment per RECIST 1.1 Secondary as determined by investigator assessment per RECIST 1.1

   Time frame: 36 months from the first administration of nivolumab

Secondary outcomes

1. PFS Progression Free Survival

   the time between the date of registration and the first date of documented progression, based on invesigator assessment (as per RECIST 1.1 criteria), or death due to any cause, whichever occurs first

   Time frame: 36 months from the first administration of nivolumab

2. OS Overall Survival

   the time from registration to the date of death from any cause

   Time frame: 36 months from the first administration of nivolumab

3. ORR (Objective Response Rate) of irradiated and non-irradiated metastases and duration of response

   determined by investigator assessment per RECIST 1.1

   Time frame: 36 months from the first administration of nivolumab

4. Incidence, nature and severity of Adverse Event (safety and tolerability)

   All Adverse Events (AEs) and laboratory abnormalities will be collected and graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v. 4.03

   Time frame: 36 months from the first administration of nivolumab

Other outcomes

1. Analysis of expression of PD-L1

   Immune checkpoint inhibitors act by shortcutting the communication between immune cells and tumor cells mediated by the PD1-PDL1 interaction. Discordant results about the correlation of PDL1 expression and response to immunotherapy exist. Thus, we will investigate the expression of PDL1 in the tumor using four available IHC test (Dako 28.8, Dako 22C3, Ventana SP142, Ventana SP 263) and we will correlate levels of expression with response to treatment.

   Time frame: 36 months from the first administration of nivolumab

2. Analysis of the genetic background of the tumor and its impact on the response to therapy

   To evaluate whether and how the initial genetic background of the renal carcinoma may impact on response to treatment in the present setting a deep sequencing analysis will be performed to assess mutational status of 578 cancer genes using the Comprehensive Cancer Design panel (Roche) and MySeq Illumina Next Generation Sequencer. The overall mutations load and the type of mutations detected will be correlated with the response to treatment.

   Time frame: 36 months from the first administration of nivolumab

3. Analysis of the immuno-modulation during therapy.

   To investigate the effect of stereotactic radiotherapy on the modulation of the immune system we propose to analyze variation in the plasma levels of soluble immune-modulators during treatment. Will be use the Bio-Plex Pro™ Human Inflammation Assay (Bioplex, Biorad) that enables to detect and quantify a panel of 24 key biomarkers of inflammation including TNF superfamily proteins, IFN family proteins, and Treg cytokines

   Time frame: 36 months from the first administration of nivolumab

4. Identification of somatic mutations associated with acquired resistance to checkpoint inhibitors

   we will investigate JAK1, JAK2 and B2M mutations by in the circulating free tumor DNA (ctDNA) obtained from the plasma samples. The ctDNA will be analyzed with a multiplexed sequencing assay that generates reads containing targeted regions along with a molecular tag that allows the accompanying optimized variant analysis software to assemble the reads into families of molecules originating from the same initial ctDNA molecules and model errors accumulated during library amplification, templating, and sequencing to accurately reconstruct the sequence of the original ctDNA molecule. The resulting sequence is then used to make variant calls down to 0.05% allele ratio with high sensitivity and specificity.

   Time frame: 36 months from the first administration of nivolumab

Publications

• Maia MC, Salgia M, Pal SK. Harnessing cell-free DNA: plasma circulating tumour DNA for liquid biopsy in genitourinary cancers. Nat Rev Urol. 2020 May;17(5):271-291. doi: 10.1038/s41585-020-0297-9. Epub 2020 Mar 17. PubMed 32203306 ↗

Individual participant data

Plan to share: No