NeoAdjuvant Pembrolizumab and STEreotactic Radiotherapy Prior to Nephrectomy for Renal Cell Carcinoma: Investigating Induced Immune Context Changes
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).
• Patient has provided written informed consent
• Male or female aged 18 years or older at written informed consent
• Histologically or cytologically confirmed diagnosis of RCC with clear cell, rhabdoid or sarcomatoid components
• Tumour stage T1B-T3, N0 or N1, M0 or low volume M1 planned for nephrectomy
• Patients must have adequate bone marrow, hepatic and renal function documented within 28 days prior to randomisation:
‣ White Blood Cell (WBC) ≥ 3 X 10\^9/L
⁃ Absolute neutrophil count (ANC) ≥1.5 X 10\^9/L
⁃ Platelets ≥ 100 X 10\^9/L
⁃ Haemoglobin ≥ 100 g/L independent of transfusion
⁃ Serum Creatinine ≤1.5 X Upper Limit of Normal (ULN) or measured or calculated CrCl calculated as per institutional standard ≥ 30 ml/min. GFR can also be used in place of serum creatinine or CrCl.
⁃ Total bilirubin ≤1.5 X ULN except for patients with known Gilbert's Syndrome
⁃ Albumin \> 30 g/L
⁃ AST and ALT ≤1.5 X ULN
⁃ INR or PT ≤1.5 X ULN unless patient is receiving anticoagulant therapy
• ECOG performance status of 0 or 1
• Women of child birth potential (WOCBP) must have a negative urine or serum pregnancy test within 72 hours prior to randomisation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• WOCBP should be willing to use two methods of birth control, or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilised or have not been free from menses for more than 1 year
• Male patients should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
⁃ Patient agrees to the collection and use of their fresh tumour samples and peripheral blood for translational research
⁃ Patient is willing and able to comply with the protocol for the duration of the study including undergoing biopsies, treatment, and scheduled visits and examination