Clinical Trials /

Nivolumab in Treating Patients With Localized Kidney Cancer Undergoing Nephrectomy

NCT03055013

Description:

This 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). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and 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 cancer.

Related Conditions:
  • Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab in Treating Patients With Localized Kidney Cancer Undergoing Nephrectomy
  • Official Title: A Phase 3 Randomized Study Comparing Perioperative Nivolumab vs. Observation in Patients With Localized Renal Cell Carcinoma Undergoing Nephrectomy (PROSPER RCC)

Clinical Trial IDs

  • ORG STUDY ID: NCI-2016-00326
  • SECONDARY ID: NCI-2016-00326
  • SECONDARY ID: EA8143
  • SECONDARY ID: EA8143
  • SECONDARY ID: EA8143
  • SECONDARY ID: U10CA180820
  • NCT ID: NCT03055013

Conditions

  • Sarcomatoid Renal Cell Carcinoma
  • Stage II Renal Cell Cancer AJCC v7
  • Stage III Renal Cell Cancer AJCC v7
  • Unclassified Renal Cell Carcinoma

Interventions

DrugSynonymsArms
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoArm I (nivolumab, nephrectomy)

Purpose

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 cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      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.

      SECONDARY OBJECTIVES:

      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.

      TERTIARY OBJECTIVES:

      I. To correlate the primary tumor's expression of programmed cell death 1 ligand 1 (PD-L1)
      with outcome.

      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
      toxicity.

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (nivolumab, nephrectomy)ExperimentalPatients receive nivolumab 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 toxicity.
    Arm II (nephrectomy)Active ComparatorPatients undergo partial or radical nephrectomy followed by observation.

      Eligibility Criteria

              Inclusion Criteria:
      
                -  ELIGIBILITY CRITERIA FOR PREREGISTRATION (STEP 0):
      
                -  Preoperative biopsy for confirmation of renal cell carcinoma (RCC) must be performed
                   within four (4) months prior to randomization
      
                     -  If biopsy was performed as part of patients standard care, and will not be
                        performed during step 0 proceed directly to randomization
      
                -  ELIGIBILITY CRITERIA FOR RANDOMIZATION (STEP 1):
      
                -  Patients with newly diagnosed higher risk RCC of any histology including sarcomatoid
                   or (if preoperative biopsy was uninformative) - "unknown" histology; RCC must have
                   been confirmed by biopsy within 4 months prior to randomization; if the biopsy clearly
                   demonstrated a benign condition or a different type of cancer, the patient is not
                   eligible to be randomized
      
                -  Clinical stage >= T2NxM0 or TanyN+ disease for which radical or partial nephrectomy is
                   planned
      
                -  Patients must have no clinical or radiological evidence of distant metastases (M0)
      
                -  No concurrent or prior systemic or local anti-cancer therapy for RCC is permitted;
                   examples of these prohibited therapies include:
      
                     -  Radical or partial nephrectomy for prior RCC
      
                     -  Metastectomy for RCC
      
                     -  Radiation therapy to the renal bed or any distant metastatic sites
      
                     -  Antineoplastic systemic therapies for RCC: i.e., chemotherapy, hormonal therapy,
                        immunotherapy, or standard or investigational agents for treatment of RCC
      
                     -  Prior treatment with an anti-programmed cell death 1 (PD-1), anti-programmed cell
                        death-ligand 1 (PD-L1), anti-PD-L2, anti-cluster of differentiation (CD)137, or
                        anti-cytotoxic T-lymphocyte protein 4 (CTLA-4) antibody, or any other antibody or
                        drug specifically targeting T-cell co-stimulation or checkpoint pathways
      
                -  Eastern Cooperative Oncology Group (ECOG) performance status: 0 or 1
      
                -  Women must not be pregnant or breast-feeding; all females of childbearing potential
                   must have a blood test or urine study within 2 weeks prior to registration to rule out
                   pregnancy; a female of childbearing potential is any woman, regardless of sexual
                   orientation or whether they have undergone tubal ligation, who meets the following
                   criteria:
      
                     -  Has not undergone a hysterectomy or bilateral oophorectomy, or
      
                     -  Has not been naturally postmenopausal for at least 24 consecutive months (i.e.,
                        has had menses at any time in the preceding 24 consecutive months)
      
                -  Women of childbearing potential and sexually active males must be strongly advised to
                   use accepted and effective methods of contraception, as described in the informed
                   consent form (ICF), or to abstain from sexual intercourse for the duration of their
                   participation in the study; women of childbearing potential should use adequate
                   methods to avoid pregnancy for 23 weeks after the last dose of nivolumab; sexually
                   active males should use adequate methods to avoid pregnancy for 31 weeks after the
                   last dose of nivolumab
      
                -  Patient must have no prior history of RCC that was resected with curative intent
                   within the past 5 years
      
                -  Patients must not have other current malignancies:
      
                     -  Adequately treated basal cell or squamous cell skin cancer, in situ cervical
                        cancer, adequately treated stage I or II cancer from which the patient is
                        currently in complete remission, or any other cancer from which the patient has
                        been disease-free for 3 years prior to the time of registration and they are not
                        receiving any current treatment
      
                     -  Prior or current prostate cancer is excluded
      
                          -  A history of superficial Ta urothelial cancer is permitted (not being
                             currently treated) but T1 or greater disease is excluded
      
                -  No active known or suspected autoimmune disease; the following are permitted: patients
                   with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune or
                   non-autoimmune condition requiring hormone replacement, asymptomatic hypothyroidism
                   not requiring treatment, psoriasis not requiring systemic treatment, or conditions not
                   expected to recur
      
                -  No ongoing condition requiring systemic treatment with either corticosteroids (> 10 mg
                   daily prednisone equivalent) or other immunosuppressive medications; no treatment with
                   other immunosuppressive agents within 14 days prior to the first dose of study drug;
                   topical, ocular, intra-articular, intranasal, inhaled steroids and adrenal replacement
                   steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of
                   active autoimmune disease.; a brief (less than 3 weeks) course of corticosteroids (any
                   amount) for prophylaxis (for example: contrast dye allergy) or for treatment of
                   non-autoimmune conditions (for example: delayed-type hypersensitivity reaction caused
                   by a contact allergen) is permitted if > 14 days since last dose
      
                -  No uncontrolled adrenal insufficiency
      
                -  No known chronic active liver disease or evidence of acute or chronic hepatitis B
                   virus (HBV) or hepatitis C (HCV)
      
                -  Patients must not have a serious intercurrent illness, including ongoing or active
                   infection requiring parental antibiotics
      
                -  No known evidence of human immunodeficiency virus (HIV) infection
      
                -  No known medical condition (e.g. a condition associated with uncontrolled diarrhea
                   such as ulcerative colitis or acute diverticulitis) that, in the investigator's
                   opinion, would increase the risk associated with study participation or interfere with
                   the interpretation of safety results
      
                -  No major surgery within 28 days prior to randomization
      
                -  Patients currently enrolled in other clinical trials testing a therapeutic
                   intervention
      
                -  White blood cells >= 2000/uL, within 4 weeks of randomization
      
                -  Absolute granulocyte count (AGC) >= 1,500/mm^3, within 4 weeks of randomization
      
                -  Platelet count >= 100,000/mm^3, within 4 weeks of randomization
      
                -  Hemoglobin >= 9.0 g/dL, within 4 weeks of randomization
      
                -  Serum creatinine =< 1.5 x upper limit of normal (ULN) or calculated creatinine
                   clearance (CrCl) >= 40 mL/min, within 4 weeks of randomization
      
                -  Total bilirubin =< 1.5 x ULN (except subjects with Gilbert syndrome, who can have
                   total bilirubin < 3.0 x ULN), within 4 weeks of randomization
      
                -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN,
                   within 4 weeks of randomization
      
                -  No history of severe hypersensitivity to a monoclonal antibody
      
                -  Signed, dated informed consent
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Recurrence-free survival (RFS)
      Time Frame:Time from randomization to disease recurrence or death from any cause, assessed up to 10 years
      Safety Issue:
      Description:Will be assessed among all randomized patients using a stratified log rank test, with nominal one-sided type I error of 2.5%. The type I error will be adjusted for interim analyses.

      Secondary Outcome Measures

      Measure:Overall survival
      Time Frame:Time from randomization to death from any cause, assessed up to 10 years
      Safety Issue:
      Description:
      Measure:RFS among patients with clear cell cancer
      Time Frame:Up to 10 years
      Safety Issue:
      Description:The stratified logrank test will be used.
      Measure:Incidence of toxicity using Common Criteria for Adverse Events version 4.0
      Time Frame:Up to 10 years
      Safety Issue:
      Description:Adverse events will be described separately for patients treated on each arm to evaluate safety and tolerability.

      Details

      Phase:Phase 3
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:National Cancer Institute (NCI)

      Last Updated

      March 5, 2018