Nivolumab in Treating Patients With Localized Kidney Cancer Undergoing Nephrectomy
Brief description of study
This randomized phase III trial compares nephrectomy (surgery to remove a kidney or part of a
kidney) with or without nivolumab in treating patients with kidney cancer that is limited to
a certain part of the body (localized). Monoclonal antibodies, such as nivolumab, may
interfere with the ability of tumor cells to grow and spread. Giving nivolumab before
nephrectomy may make the tumor smaller and reduce the amount of normal tissue that needs to
be removed, and after nephrectomy to increase survival. It is not yet known whether nivolumab
and nephrectomy is more effective than nephrectomy alone in treating patients with kidney
Clinical Study Identifier: NCT03055013
Detailed Study Description
I. To compare recurrence-free survival (RFS) between patients with locally advanced renal
cell carcinoma randomly assigned to perioperative nivolumab in conjunction with radical or
partial nephrectomy with patients randomized to surgery alone.
I. To evaluate for differences in recurrence-free survival associated with perioperative
nivolumab compared to surgery alone among the subset of patients with clear cell histology.
II. To compare the overall survival between patients randomized to perioperative nivolumab in
addition to resection to patients randomized to primary tumor resection alone.
III. To describe the safety and tolerability of perioperative nivolumab.
I. To correlate the primary tumor's expression of programmed cell death 1 ligand 1 (PD-L1)
II. To correlate the expression of PD-L1 on tumor tissue at recurrence with outcome.
III. To archive images for central confirmation of recurrence and for future correlative work
with American College of Radiology Imaging Network (ACRIN), including markers predicting
outcome or response.
IV. To prospectively collect tumor and biologic specimens (e.g., serum, peripheral blood
mononuclear cells [PBMCs]) for future correlative studies.
V. To characterize the pharmacokinetics of nivolumab and explore exposure response
relationships with respect to safety and efficacy.
VI. To characterize the immunogenicity of nivolumab. VII. To evaluate differences in change
from baseline in patient-reported symptoms and toxicities among patients randomized to
treatment with nivolumab compared to surgery alone.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive nivolumab intravenously (IV) over 60 minutes on day 1. Treatment
repeats every 14 days for 2 courses. Patients then undergo partial or radical nephrectomy.
Patient then receive nivolumab IV on day 1. Treatment repeats every 14 days for 6 courses,
and then every 28 days for 6 courses in the absence of disease progression or unacceptable
ARM II: Patients undergo partial or radical nephrectomy followed by observation.
After completion of study treatment, patients are followed up every 3 months for 2 years,
every 6 months for 3 years, and every 12 months for 5 years.