This is a prospective, open label, phase II, randomised, non-comparative clinical trial, evaluating changes in tumour-responsive T-cells following neoadjuvant stereotactic ablative body radiotherapy (SABR) with or without pembrolizumab, prior to nephrectomy, in patients with localised primary clear cell renal cell carcinoma (ccRCC).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Pembrolizumab 200 mg tobe administered as a 30 minute IV infusion every 21 days for 3 cycles
42Gy delivered in 3 fractions
Partial or total nephrectomy performed 9-12 weeks after first dose of Pembrolizumab
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia
RECRUITINGPeter MacCallum Cancer Centre
Melbourne, Victoria, Australia
RECRUITINGmPR post-SABR with or without pembrolizumab
The mPR rate is defined as \<10% residual tumour at post-nephrectomy specimens
Time frame: At nephrectomy performed 9-12 weeks after first dose of pembrolizumab
CD8+ TRM in baseline biopsy and post-nephrectomy specimen, all measured as a continuous variable.
To describe changes in tumour-responsive T-cells, TRM CD8+ T-cells from baseline to post-nephrectomy in patients treated with SABR with or without pembrolizumab treatment followed by nephrectomy
Time frame: Baseline and at nephrectomy performed 9-12 weeks after first dose of pembrolizumab
TCF-1 + tumour infiltrating lymphocytes (TILs) in baseline biopsy and post-nephrectomy specimen, measured as a continuous variable
To describe changes in TCF-1+ T-cells from baseline to post-nephrectomy in patients treated with SABR with or without pembrolizumab treatment followed by nephrectomy
Time frame: Baseline and at nephrectomy performed 9-12 weeks after first dose of pembrolizumab
Immune response cells in baseline biopsy and post-nephrectomy specimen
Change in immune response from baseline to post-nephrectomy
Time frame: Baseline and at nephrectomy performed 9-12 weeks after first dose of pembrolizumab
The tumour-responsive TRM cells inclusive of CD4+ and CD8+ compartments
Percentage of tumour responsive T-cells (inclusive CD4/CD8) after neo-adjuvant treatment
Time frame: 2 weeks prior to nephrectomy
Safety of SABR with or without pembrolizumab in the neo-adjuvant setting
Adverse events, as measured by CTCAE v5.0
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Time frame: 60 days post nephrectomy
Change in immune response associated with mPR
Immune response cells in baseline biopsy and post-nephrectomy specimens
Time frame: Baseline and at nephrectomy performed 9-12 weeks after first dose of pembrolizumab
Change in PD-L1 and PD-L2 expression in tumour
PD-L1 and PD-L2 expression in baseline biopsy and post-nephrectomy specimens
Time frame: Baseline and at nephrectomy performed 9-12 weeks after first dose of pembrolizumab