Stereotactic Radiotherapy and Anti-PD1 Antibody (Pembrolizumab) for Oligometastatic Renal Tumours

Inclusion Criteria

• Has provided written informed consent for the trial.
• Be at least 18 years of age on day of signing informed consent.
• Have oligometastases (1-5 metastases), and measurable disease based on RECIST 1.1.
• Participants must have a histologically or cytologically confirmed metastatic renal cell carcinoma. Oligometastatic lesions do not need to be biopsied but they must be clinically consistent to represent metastatic disease.
• Patient can either be treatment naïve or have previously received up to 2 lines of systemic treatment (eg. Pazopanib or Sunitinib). The total number of metastases throughout the pre-trial period should not number more than 5.
• Must have had surgical consideration for metastasectomy and thought appropriate for SABR due to medical inoperability, technical factors or patient declining surgery.
• Must have at least one metastasis for which SABR is technically deliverable.
• Be willing to provide archival tissue from a previously biopsied or excised primary or metastatic RCC lesion (if available). If safe to do so, a request for newly obtained specimen (obtained up to 4 weeks prior to initiation of treatment) will be made, however participation for this biopsy is entirely optional.
• Have a performance status of 0-2 on the ECOG Performance Scale
• Demonstrate adequate organ function as defined below all screening labs should be performed within 10 days of registration.
• Absolute neutrophil count (ANC) - ≥1.5 X 10^9/L
• Platelets - ≥100 X 10^9/L
• Hemoglobin - ≥90 g/L or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
• Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) - ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for participant with creatinine levels > 1.5 X institutional ULN
• Serum total bilirubin - ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for participants with total bilirubin levels > 1.5 ULN
• AST (SGOT) and ALT (SGPT) - ≤ 2.5 X ULN OR ≤ 5 X ULN for participants with liver metastases
• Albumin - >2.5 mg/dL
• International Normalized Ratio (INR) or Prothrombin Time (PT) - ≤1.5 X ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Activated Partial Thromboplastin Time (aPTT) - ≤1.5 X ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Life expectancy > 12 months.
• Be willing and able to comply with all study requirements, including treatment, attending assessments and follow-up.
• Female participant of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female participants of childbearing potential should be willing to use 2 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 (see Section 9.4.2: Contraception). Participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
• Male participants 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

Exclusion Criteria

• Based on clinician assessment of disease volume and rate of progression of patient's tumor deposits, the patient requires immediate TKI therapy.
• Has had previous high dose radiotherapy (biological equivalent of 30Gy in 10#) to an area to be treated which includes vertebral bodies (see below).

Note: Previous high dose radiotherapy is defined as a biological equivalent dose to above that of 30 Gy in 10 fractions using an alph