Efficacy of PErioperative PEmbrolizumab Treatment in Patients With Resectable Metastases From Kidney Cancer. (The PE-PE Study).
This is a phase II trial aiming at assessing the efficacy of pembrolizumab to delay tumor progression in patients with oligometastatic clear cell metastatic Renal Cell Carcinoma (mRCC). Eligible patients for this trial should have received previous surgery for primary tumor and have maximum of three metastases considered eligible for radical therapy (surgery or metastases directed radiotherapy). Eligible patients will be randomized 2:1 to receive: * ARM A: pembrolizumab at flat dose of 400 mg every six weeks for a total of 9 cycles (one year of therapy) and metastasis directed treatment (surgery or RT) from day 21 of cycle 1 to day 42 of cycle 1; or * ARM B: local therapy alone within 42 days.
⁃ Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of clear cell renal cell carcinoma will be enrolled in this study.
⁃ Have undergone a partial nephrectomy or radical complete nephrectomy with negative surgical margins.
⁃ Evidence of oligo-metastatic disease eligible for local treatment with radiotherapy or surgery, defined as:
∙ Appearance of new metastases within 5 years from previous eradication of primary tumors or previous metastasectomy.
‣ Presence of maximum 3 metastases in the same site or in different sites with the exception of bone metastases that cannot exceed the number of 2 if they are the sole disease site or one in case of multiple sites.
‣ Each metastasis should be less than 3 cm in the maximum diameter and less than 5 cm in the sum of the longest tumor diameters (this evaluation should apply also for lymph nodes).
⁃ Has received no prior systemic therapy for Renal Cell Carcinoma (RCC).
⁃ Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 7 days of before the start of study intervention.
⁃ The participant (or legally acceptable representative) has provided documented informed consent/assent for the study.
⁃ Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a primary tumor or tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slide. Newly obtained biopsies are preferred to archived tissue.
⁃ Female participants:
⁃ A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
∙ Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 of the Study protocol OR
‣ A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days (corresponding to time needed to eliminate any study treatment(s)) plus 30 days (a menstruation cycle) for study treatments with risk of genotoxicity after the last dose of study treatment.
⁃ Adequate organ function defined as:
• System - Laboratory Value
• Hematological
• Absolute neutrophil count (ANC): ≥ 1500/μl
• Platelets: ≥ 100 000/μl
• Hemoglobin: ≥ 9.0 g/dL or ≥ 5.6 mmol/L
• Renal
• Creatinine: ≤1.5 x Upper Limit of Normal (ULN) OR
• Measured or calculated creatinine clearance: ≥ 30 mL/min for participant with creatinine levels \> 1.5 x institutional ULN (GFR can also be used in place of creatinine or CrCl)
• Hepatic
• Total bilirubin: ≤ 1.5 x ULN OR direct bilirubin ≤ ULN for participants with total bilirubin levels \> 1.5 x ULN
• Aspartate transaminase (AST or SGOT) and alanine transaminase (ALT or SGPT): ≤ 2.5 x ULN (≤ 5 ULN for participants with liver metastases)
• Coagulation
• International normalized ratio (INR) OR prothrombin time (PT)
• Activated partial thromboplastin time (aPTT): ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants