A Study to Evaluate the Safety of Nivolumab and Ipilimumab in Subjects With Previously Untreated Advanced or Metastatic Renal Cell Cancer
- Registration Number
- NCT02982954
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
To investigate the safety of Nivolumab in combination with Ipilimumab in subjects with previously untreated advanced or metastatic Renal Cell Cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 211
-
Type of Participant and Target Disease Characteristics
-
Advanced or metastatic RCC
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Histologically confirmed, previously untreated (treatment-naive) RCC
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No prior systemic therapy for RCC except for one prior adjuvant or neoadjuvant therapy for completely resectable RCC
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Measurable disease as per RECIST 1.1. Subject must have extracranial metastasis as measurable disease
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Karnofsky Performance Status (KPS) of at least 70% for Cohort 1, 2, and 3; KPS of 50-60% for Cohort 4
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Tumor tissue need be received by the central vendor (block or unstained slides). Note: Fine Needle Aspiration (FNA)and bone metastases samples are not acceptable for submission.
-
Medical Conditions
- Subjects with any active autoimmune disease or a history of known autoimmune disease
- Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured
- Known HIV or AIDS-related illness
- Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection.
-
Prior/Concomitant Therapy
- Prior systemic treatment in the metastatic setting with Vascular epithelial growth factor(VEGF) or VEGF receptor targeted therapy
- Prior treatment with an anti-Programmed Death (PD) -1, anti-PD-L1, anti-PD-L2, anti-cluster of differentiation 137 (CD137), or anti-cytotoxic T-lymphocyte-associated antigen 4(CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. This includes the utilization of these agents in the neo-adjuvant or adjuvant setting.
- Anti-cancer therapy less than 28 days prior to the first dose of study drug or palliative, focal radiation therapy less than 14 days prior to the first dose of study drug.
Other protocol defined inclusion/exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ccRCC KPS ≥ 70% Nivolumab Clear-Cell Renal Cell Carcinoma (ccRCC) with Karnofsky Performance Status (KPS) ≥ 70% Non-ccRCC, KPS ≥ 70% Nivolumab Non Clear-Cell Renal Cell Carcinoma (nccRCC) with KPS ≥ 70% ccRCC KPS ≥ 70% Ipilimumab Clear-Cell Renal Cell Carcinoma (ccRCC) with Karnofsky Performance Status (KPS) ≥ 70% Non-ccRCC, KPS ≥ 70% Ipilimumab Non Clear-Cell Renal Cell Carcinoma (nccRCC) with KPS ≥ 70% RCC with non-active Brain Mets, KPS ≥70% Nivolumab Renal Cell Carcinoma (RCC) with non-active Brain Metastases, with KPS ≥70% RCC with non-active Brain Mets, KPS ≥70% Ipilimumab Renal Cell Carcinoma (RCC) with non-active Brain Metastases, with KPS ≥70% any RCC with KPS 50%-60% Nivolumab Renal Cell Carcinoma (RCC), regardless of any histology or existing non-active brain metastasis, with KPS 50%-60% any RCC with KPS 50%-60% Ipilimumab Renal Cell Carcinoma (RCC), regardless of any histology or existing non-active brain metastasis, with KPS 50%-60%
- Primary Outcome Measures
Name Time Method Number of Participants With High Grade (Grade 3-4) Immune Mediated Adverse Events (IMAEs) Approximately 39 Months Number of participants with IMAEs in the following categories: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity
Number of Participants With High Grade (Grade 5) Immune Mediated Adverse Events (IMAEs) Approximately 39 Months Number of participants with IMAEs in the following categories: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity
- Secondary Outcome Measures
Name Time Method Number of Participants Who Received Hormone Replacement Therapy for High Grade (Grades 3-5) Immune Mediated Adverse Events (IMAEs) From first dose up to 100 days post last dose (up to approximately 29 months) The number of participants who received Hormone Replacement Therapy for experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the last dose (2) regardless of causality (3) with no clear alternate etiology based on investigator assessment, or with an immune-mediated component and (4) treated with immune-modulating medication. Grade 3= Severe reaction, Grade 4 = Life-threatening, Grade 5 = Death
Time to Response Rate (TRR) From the date of first dose to first documented CR or PR, up to approximately 15 months TTR is defined as the median percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable participants. Best overall response is defined as the best response recorded from the start of the study treatment until the end of treatment. The participant's best overall response assignment will depend on the findings of both target and non-target disease and will also take into consideration the appearance of new lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all lesions and normalization of tumor marker level. All lymph nodes (whether target or non-target) must be non-pathological in size (\< 10mm short axis).
Median Progression Free Survival (PFS) From first dose to the date of the first documented progressive disease, up to approximately 12 months PFS is defined as the time from first dose to the date of the first documented progressive disease (PD) as determined by the investigator (per RECIST 1.1 criteria or clinical) or death due to any cause whichever occur first. Progressive disease is defined as progression of existing non-target lesions or at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Number of Participants Who Received Immune Modulating Medication for High Grade (Grades 3-5) Immune Mediated Adverse Events (IMAEs) From first dose up to 100 days post last dose (up to approximately 29 months) The number of participants who received immune modulating medication for participants experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the last dose (2) regardless of causality (3) with no clear alternate etiology based on investigator assessment, or with an immune-mediated component and (4) treated with immune-modulating medication. Grade 3= Severe reaction, Grade 4 = Life-threatening, Grade 5 = Death
Time to Onset of Grade 3-5 Immune Mediated Adverse Events (IMAEs) From first dose to the earliest IMAE (grade 3-5) event onset date (up to approximately 116 weeks) Time to onset is defined as the duration of time in weeks from the first dosing to the immune modulating adverse event onset date. Participants experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the last dose (2) regardless of causality (3) with no clear alternate etiology based on investigator assessment, or with an immune-mediated component and (4) treated with immune-modulating medication. Grade 3= Severe reaction, Grade 4 = Life-threatening, Grade 5 = Death
Time to Resolution of Grade 3-5 Immune Mediated Adverse Events (IMAEs) From the IMAE onset date to the IMAE end date, up to approximately 194 weeks Time to resolution is defined as the longest time from IMAE onset date to complete resolution or improvement to the grade at baseline experienced by the participant (the IMAE end date). Participants experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the last dose (2) regardless of causality (3) with no clear alternate etiology based on investigator assessment, or with an immune-mediated component and (4) treated with immune-modulating medication. Grade 3= Severe reaction, Grade 4 = Life-threatening, Grade 5 = Death
Number of Participants Who Received ≥ 40mg of Prednisone for High Grade (Grades 3-5) Immune Mediated Adverse Events (IMAEs) From first dose up to 100 days post last dose (up to approximately 29 months) The number of participants who received ≥ 40mg of prednisone for high grade (grades 3-5) IMAEs. Participants experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the last dose (2) regardless of causality (3) with no clear alternate etiology based on investigator assessment, or with an immune-mediated component and (4) treated with immune-modulating medication. Grade 3= Severe reaction, Grade 4 = Life-threatening, Grade 5 = Death
Objective Response Rate (ORR) From first dose up to the date of objectively documented progression or the date of subsequent therapy, whichever occurs first (up to approximately 26 months) ORR is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable participants. Best overall response is defined as the best response recorded from the start of the study treatment until the end of treatment. The participant's best overall response assignment will depend on the findings of both target and non-target disease and will also take into consideration the appearance of new lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all lesions and normalization of tumor marker level. All lymph nodes (whether target or non-target) must be non-pathological in size (\< 10mm short axis).
Duration of Response (DOR) From first confirmed response to the date of the first documented tumor progression or death, up to approximately 48 months DOR is defined as the time between the date of first confirmed response to the date of the first documented tumor progression per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, or death due to any cause, whichever occurs first. DOR will be computed for participants who achieve partial response (PR) or complete response (CR) only. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all lesions and normalization of tumor marker level. All lymph nodes (whether target or non-target) must be non-pathological in size (\< 10mm short axis).
Trial Locations
- Locations (59)
Los Angeles Cancer Network
🇺🇸Los Angeles, California, United States
Tennessee Oncology, PLLC - SCRI - PPDS
🇺🇸Chattanooga, Tennessee, United States
Hollings Cancer Center
🇺🇸Charleston, South Carolina, United States
University of Wisconsin Clinical Science Center
🇺🇸Madison, Wisconsin, United States
Local Institution - 0028
🇺🇸Fayetteville, Arkansas, United States
Coastal Integrative Cancer Care
🇺🇸San Luis Obispo, California, United States
Hattiesburg Clinic
🇺🇸Hattiesburg, Mississippi, United States
Sharp Memorial Hospital
🇺🇸San Diego, California, United States
Broome Oncology
🇺🇸Johnson City, New York, United States
Local Institution - 0052
🇺🇸New York, New York, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
University Of Miami/Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Yakima Valley Memorial Hospital/North Star Lodge
🇺🇸Yakima, Washington, United States
Local Institution - 0042
🇺🇸Fairfax, Virginia, United States
University of Washington - Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Virginia Cancer Institute
🇺🇸Richmond, Virginia, United States
Bon Secours St Francis Hospital
🇺🇸Midlothian, Virginia, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Local Institution - 0002
🇺🇸Nashville, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Southdale Cancer Clinic
🇺🇸Burnsville, Minnesota, United States
Park Nicollet Clinic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Local Institution - 0009
🇺🇸Coon Rapids, Minnesota, United States
Medical Oncology Associates
🇺🇸Spokane, Washington, United States
Ironwood Cancer And Research Centers, Pc
🇺🇸Chandler, Arizona, United States
Northwest Alabama Cancer Center, Pc
🇺🇸Muscle Shoals, Alabama, United States
Alaska Urological Institute dba Alaska Clinical Research Center
🇺🇸Anchorage, Alaska, United States
eCare
🇺🇸Encinitas, California, United States
Kaiser Permanente Medical Group - Southern California
🇺🇸Riverside, California, United States
UCLA Hematology Oncology
🇺🇸Los Angeles, California, United States
Torrance Health Association
🇺🇸Redondo Beach, California, United States
Central Coast Med Oncology
🇺🇸Santa Maria, California, United States
Florida Cancer Specialists S.
🇺🇸Fort Myers, Florida, United States
Emory University - Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Florida Cancer Specialists
🇺🇸Saint Petersburg, Florida, United States
Illinois Cancer Specialists
🇺🇸Niles, Illinois, United States
Local Institution - 0012
🇺🇸Fort Wayne, Indiana, United States
Cancer Center Of Kansas
🇺🇸Wichita, Kansas, United States
Jackson Oncology Associates, Pllc
🇺🇸Jackson, Mississippi, United States
HCA Midwest Division
🇺🇸Kansas City, Missouri, United States
Local Institution - 0023
🇺🇸Hackensack, New Jersey, United States
University Of New Mexico
🇺🇸Albuquerque, New Mexico, United States
Maimonides Medical Center
🇺🇸Brooklyn, New York, United States
St. Francis Cancer Treatment Center
🇺🇸Grand Island, New York, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Southeastern Medical Oncology Center
🇺🇸Goldsboro, North Carolina, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Local Institution - 0071
🇺🇸Pittsburgh, Pennsylvania, United States
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
Charleston Hematology Oncology Associates, Pa
🇺🇸Charleston, South Carolina, United States
Oklahoma Cancer Specialists and Research Institute, LLC-Clinical Research
🇺🇸Tulsa, Oklahoma, United States
Texas Oncology
🇺🇸San Antonio, Texas, United States
Texas Oncology-Fort Worth 12th Ave
🇺🇸Fort Worth, Texas, United States
Texas Oncology-Midland Allison Cancer Center
🇺🇸Midland, Texas, United States
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
UF Health Cancer Center at Orlando Health
🇺🇸Orlando, Florida, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Pacific Shores Medical Group
🇺🇸Long Beach, California, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States