An Investigational Immuno-therapy Safety Trial of Nivolumab in Patients With Advanced or Metastatic Renal Cell Carcinoma (CheckMate 374)

A Phase 3b/4 Safety Trial of Nivolumab (BMS-936558) in Subjects With Advanced or Metastatic Renal Cell Carcinoma (CheckMate 374: CHECKpoint Pathway and Nivolumab Clinical Trial Evaluation 374)

This study will generate safety data on Nivolumab given by itself in treatment of advanced Renal Cell Carcinoma (RCC). The primary objective of this study is to assess immune related side effects, also known as immune-mediated adverse events (IMAEs), in patients treated with Nivolumab.

Study Overview

• Status: Completed
• Conditions: Renal Cell Carcinoma
• Intervention / Treatment: Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 197
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Local Institution - 0030
  • California
    • Bakersfield, California, United States, 93309
      • Comprehensive Blood and Cancer Center
    • Fullerton, California, United States, 92835
      • St. Jude Hospital Yorba Linda
    • Redondo Beach, California, United States, 90277
      • Cancer Care Associates Medical Group, Inc.
    • Santa Barbara, California, United States, 93105
      • Sansum Santa Barbara Medical Foundation Clinic
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
    • Grand Junction, Colorado, United States, 81501
      • Local Institution - 0028
    • Lakewood, Colorado, United States, 80228
      • Local Institution - 0018
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Local Institution - 0008
    • Miami, Florida, United States, 33176
      • Baptist Health Medical Group Oncology
    • Saint Petersburg, Florida, United States, 33705
      • Local Institution - 0007
    • Tampa, Florida, United States, 33612-9497
      • Local Institution - 0054
  • Illinois
    • Niles, Illinois, United States, 60714
      • Illinois Cancer Specialists
  • Indiana
    • Fort Wayne, Indiana, United States, 46845
      • Local Institution - 0052
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • HCA Midwest Division
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Southeast Nebraska Hematology & Oncology Consultants, P.C.
    • Omaha, Nebraska, United States, 68130
      • Local Institution - 0011
    • Omaha, Nebraska, United States, 68130
      • Urology Cancer Center Laboratory
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Local Institution - 0014
  • New York
    • Buffalo, New York, United States, 14263
      • Local Institution - 0053
    • Johnson City, New York, United States, 13790
      • Broome Oncology
    • New York, New York, United States, 10065
      • Local Institution - 0055
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74146
      • Local Institution - 0001
  • Oregon
    • Portland, Oregon, United States, 97213-2982
      • Local Institution - 0016
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Local Institution - 0020
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Local Institution - 0005
    • Germantown, Tennessee, United States, 38138
      • Local Institution - 0012
    • Nashville, Tennessee, United States, 37203
      • Local Institution - 0004
  • Texas
    • Dallas, Texas, United States, 75246
      • Local Institution - 0015
    • Fort Worth, Texas, United States, 76104
      • The Center for Cancer and Blood Disorders
    • Houston, Texas, United States, 77024
      • Local Institution - 0034
    • San Antonio, Texas, United States, 78217
      • Local Institution - 0021
    • Sherman, Texas, United States, 75090-0504
      • Texas Cancer Center - Sherman
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Local Institution - 0032
    • Richmond, Virginia, United States, 23230
      • Local Institution - 0047
    • Roanoke, Virginia, United States, 24014
      • Local Institution - 0017
  • Washington
    • Seattle, Washington, United States, 98109
      • Local Institution - 0039

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Advanced or Metastatic renal cell carcinoma (RCC)

• Predominant clear cell histology:

  1. At least 1 but no more than 2 prior systemic anti vascular endothelial growth factor (anti-VEGF) treatments
  2. No more than 3 total prior systemic treatment regimens in the advanced or metastatic setting
  3. Subjects with prior treatment with a mechanistic target of rapamycin (mTOR) are eligible
• Non-clear cell histology: 0-3 prior systemic therapies and may include mTOR inhibitor
• Brain metastases allowed if asymptomatic, without edema, and not receiving corticosteroids or radiation
• Performance Status (PS): ≥ 70% Karnofsky Performance Scale (KPS)
• All Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic scores allowed

Exclusion Criteria:

• Subjects with any active autoimmune disease or a history of known autoimmune disease
• History of severe hypersensitivity reaction to other monoclonal antibodies
• Prior malignancy, active within the last 3 years, except for locally curable cancers which have been apparently cured
• Known HIV or AIDS-related illness
• Any positive tests for Hepatitis B or Hepatitis C virus indicating acute or chronic infection

Other protocol-defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nivolumab; Nivolumab dose as specified	Drug: Nivolumab; Other Names: Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs)	IMAEs were tabulated using worst grade per Common Terminology Criteria for Adverse Events, National Cancer Institute (NCI CTCAE) Version 4.0 criteria by system organ class and MedDRA version 20.1 preferred term.	Up to 100 days of the last dose of study drug (Approximately 2 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Time to Onset of High Grade (Grade 3-5) Immune Mediated Adverse Events	Time to onset was calculated from first dosing date to the event onset date. If a participant never experienced the given AE, the participant will be censored at the last contact date.	Up to 100 days of the last dose of study drug (Approximately 10 months up to 26 months)
Median Time to Resolution of High Grade (Grade 3-5) Immune Mediated Adverse Events	Time-to resolution of grade 3-5 AE was defined as the longest time from onset to complete resolution or improvement to the grade at baseline among all clustered select AEs in the category experienced by the participant. Events which worsened into grade 5 events (death) or have a resolution date equal to the date of death are considered unresolved. If a clustered AE is considered as unresolved, the resolution date will be censored to the last known date alive.	From onset of grade 3-5 IMAEs to resolution of IMAEs (Approximately 4 years and 7 months)
Percentage of Participants Who Receive Immune Modulating Medication for the Immune-Mediated Event (Any Grade)	Immune modulating medication includes corticosteroids, infliximab, cyclophosphamide, Intravenous immunoglobulin (IVIG), and mycophenolate mofetil	Up to 100 days of the last dose of study drug (Approximately 3 years and 2 months)
Percentage of Participants Who Receive More Than Equal to (>=) 40 mg Prednisone Equivalents for the Immune-Mediated Event	Immune modulating medication includes corticosteroids, infliximab, cyclophosphamide, Intravenous immunoglobulin (IVIG), and mycophenolate mofetil	Up to 100 days of the last dose of study drug (Approximately 3 years and 2 months)
Total Duration of All Immune Modulating Medications Given for the Immune-Mediated Event	Immune modulating medication includes corticosteroids, infliximab, cyclophosphamide, Intravenous immunoglobulin (IVIG), and mycophenolate mofetil.	From the initiation of Immune modulating medication to discontinuation (approximately 4 years and 9 months).)
Percentage of Participants With a Resolution of IMAEs After Initiating Immune Modulating Medication	Percentage of participants with a resolution of IMAEs after initiating immune modulating medication.	Up to 100 days of the last dose of study drug (Approximately 2 years)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2016
• Primary Completion (Actual): March 19, 2018
• Study Completion (Actual): May 24, 2021

Study Registration Dates

• First Submitted: November 2, 2015
• First Submitted That Met QC Criteria: November 2, 2015
• First Posted (Estimate): November 4, 2015

Study Record Updates

• Last Update Posted (Actual): October 27, 2022
• Last Update Submitted That Met QC Criteria: October 25, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: CA209-374; 2015-003286-28 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No