A Dose Frequency Optimization,Trial of Nivolumab 240 mg Every 2 Weeks vs Nivolumab 480 mg Every 4 Weeks in Subjects With Advanced or Metastatic Non-small Cell Lung Cancer Who Received Up to 12 Months of Nivolumab at 3 mg/kg or 240 mg Every 2 Weeks
- Conditions
- Lung Cancer
- Interventions
- Biological: Nivolumab
- Registration Number
- NCT02713867
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The primary objective of this study is to compare PFS (progression-free survival) rate at 6 months and at 1 year after randomization, of Nivolumab 480 mg every 4 weeks with nivolumab 240 mg every 2 weeks in subjects with advanced/metastatic (Stage IIIb/IV) NSCLC (non-Sq and Sq).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 363
- Histologically or cytologically documented Squamous or non-Squamous Non-small cell lung cancer (NSCLC) (Stage IIIB/IV), or recurrent or progressive disease following multimodal therapy
- Patients must have received pre-study nivolumab for up to 12 months and have 2 consecutive tumor assessments confirming Complete response (CR), Partial response (PR), or Stable disease (SD)
- Measurable disease before start of pre-study nivolumab treatment
- Eastern Cooperative Oncology Group (ECOG) Performance status (PS) 0-2
- Carcinomatous meningitis
- Untreated, symptomatic Central nervous system (CNS) metastases
- Symptomatic interstitial lung disease
Other protocol defined inclusion/exclusion criteria could apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Nivolumab 480 mg Nivolumab Nivolumab 480 mg Every 4 Weeks Nivolumab 240 mg Nivolumab Nivolumab 240 mg Every 2 Weeks
- Primary Outcome Measures
Name Time Method Progression Free Survival Rate (PFSR) at 6 Months At 6 Months The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as 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. Note: the appearance of one or more new lesions is also considered progression.
Progression Free Survival Rate (PFSR) at 12 Months At 12 Months The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as 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. Note: the appearance of one or more new lesions is also considered progression.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) Rate at 12 Months At 12 Months The proportion of participants alive at 12 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive.
Overall Survival (OS) Rate up to 60 Months From randomization to the date of death, Up to 60 Months The proportion of participants alive up to 60 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive.
Overall Survival Rate by Response Criteria at 12 Months 12 Months The proportion of participants alive at 12 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive.
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Stable Disease (SD): Neither sufficient shrinkage from the baseline study to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
OS rate by response did not have data collected after 12 months randomization.Percentage of Participants With an Adverse Events (AEs) Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) Percentage of participants with an Adverse Event due to any cause
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.Percentage of Participants With an Adverse Events Leading to Discontinuation (AEsDC) Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) Percentage of Participants with an Adverse Event leading to discontinuation (AEsDC) due to any cause.
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.Percentage of Participants Who Experienced Death Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) Percentage of Participants who experienced Death due to any cause
Progression Free Survival Rate (PFSR) at 24 Months At 24 Months The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as 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. Note: the appearance of one or more new lesions is also considered progression.
Progression Free Survival Rate (PFSR) by Tumor Histology at 12 Months At 12 Months The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as 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. Note: the appearance of one or more new lesions is also considered progression.
Percentage of Participants With an Immune Mediated Adverse Events (IMAEs) Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) Percentage of Participants with an Immune Mediated Adverse Events treated with Immune-Modulating Medication
Percentage of Participants With an Event of Special Interest (ESI) Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) Other ESI included the following categories: demyelination, encephalitis, Guillain-Barré syndrome (GBS), myasthenic syndrome, pancreatitis, uveitis, myositis, myocarditis, rhabdomyolysis, and Graft Versus Host Disease (GVHD).
Percentage of Participants With an Serious Adverse Events (SAEs) Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) Percentage of participants with an Serious Adverse Event due to any cause.
A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose:
1. results in death
2. is life-threatening (defined as an event in which the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe)
3. requires inpatient hospitalization or causes prolongation of existing hospitalization
4. results in persistent or significant disability/incapacity
5. is a congenital anomaly/birth defect
6. is an important medical event (defined as a medical event(s) that may not be immediately life-threatening or result in death or hospitalization but, based upon appropriate medical and scientific judgment, may jeopardize the participant or may require intervention \[eg, medical, surgical\] to prevent one of the other serious outcomes listed in the definition above.)Progression Free Survival Rate (PFSR) by Response Criteria at 12 Months At 12 Months The proportion of participants remaining progression free and surviving at 12 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Stable Disease (SD): Neither sufficient shrinkage from the baseline study to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.Overall Survival Rate by Histology at 12 Months at 12 Months The proportion of participants alive at 12 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive.
OS rate by histology did not have data collected after 12 months randomization.Percentage of Participants With an Select Adverse Events Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) Percentage of Participants with an Select Adverse Event due to any cause
Select adverse events include adverse events in the following systems: Gastrointestinal, Hepatic, Pulmonary, Renal, Skin, Hypersensitivity/Infusion reaction and Endocrine.Number of Participants With Laboratory Test Abnormalities Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months) Number of participants with any laboratory test result that is clinically significant or meets the definition of an SAE (Grade 3+4 combined)
Trial Locations
- Locations (116)
Local Institution - 0089
🇺🇸Hollywood, Florida, United States
Hematology And Oncology Associates
🇺🇸Canton, Ohio, United States
Local Institution - 0116
🇺🇸Tupelo, Mississippi, United States
Local Institution - 0035
🇺🇸Albany, New York, United States
Local Institution - 0038
🇺🇸Fort Myers, Florida, United States
Mercy Medical Research Institute
🇺🇸Springfield, Missouri, United States
Hematology Oncology Consultants, Pc
🇺🇸Medford, Oregon, United States
Texas Oncology, P.A.
🇺🇸Sugar Land, Texas, United States
Local Institution - 0011
🇺🇸Dallas, Texas, United States
St Jude Hospital Yorba Linda
🇺🇸Fullerton, California, United States
Local Institution - 0143
🇺🇸Urbana, Illinois, United States
Local Institution - 0130
🇺🇸Vallejo, California, United States
Local Institution - 0136
🇺🇸Southfield, Michigan, United States
Local Institution - 0001
🇺🇸Pensacola, Florida, United States
Local Institution - 0044
🇺🇸Santa Maria, California, United States
Local Institution - 0008
🇺🇸Athens, Georgia, United States
Local Institution - 0122
🇺🇸Fort Collins, Colorado, United States
Local Institution - 0129
🇺🇸Massillon, Ohio, United States
Local Institution - 0127
🇺🇸Pinehurst, North Carolina, United States
Local Institution - 0023
🇺🇸Abilene, Texas, United States
Texas Oncology - Amarillo
🇺🇸Amarillo, Texas, United States
Local Institution - 0141
🇺🇸Lebanon, New Hampshire, United States
Local Institution - 0013
🇺🇸Johnson City, New York, United States
Local Institution - 0025
🇺🇸Flower Mound, Texas, United States
Local Institution - 0010
🇺🇸Santa Barbara, California, United States
Local Institution - 0099
🇺🇸Fort Wayne, Indiana, United States
Local Institution - 0137
🇺🇸New Orleans, Louisiana, United States
Southern California Permanente Medical Group
🇺🇸Bellflower, California, United States
Torrance Health Association
🇺🇸Redondo Beach, California, United States
Local Institution - 0039
🇺🇸Saint Petersburg, Florida, United States
Local Institution - 0026
🇺🇸Ocala, Florida, United States
Local Institution - 0109
🇺🇸Brewer, Maine, United States
Local Institution - 0118
🇦🇺Waratah, New South Wales, Australia
Shenandoah Oncology
🇺🇸Winchester, Virginia, United States
Mary Bird Perkins Cancer Center
🇺🇸Baton Rouge, Louisiana, United States
Local Institution - 0119
🇺🇸Midland, Texas, United States
Local Institution - 0145
🇨🇦Montreal, Quebec, Canada
Local Institution - 0031
🇺🇸Vancouver, Washington, United States
Local Institution - 0117
🇦🇺Westmead,, New South Wales, Australia
Local Institution - 0055
🇦🇺Kurralta Park, South Australia, Australia
Local Institution - 0034
🇺🇸Wichita Falls, Texas, United States
Yakima Valley Memorial Hospital/North Star Lodge
🇺🇸Yakima, Washington, United States
Local Institution - 0073
🇩🇪Berlin, Germany
Local Institution - 0053
🇦🇺Heidelberg, Victoria, Australia
Local Institution - 0075
🇫🇷Suresnes Cedex, France
Local Institution - 0064
🇩🇪Kassel, Germany
Local Institution - 0063
🇩🇪Dresden, Germany
Local Institution - 0081
🇫🇷Angers, France
Local Institution - 0072
🇫🇷Mulhouse, France
Local Institution - 0079
🇫🇷Tours, France
Local Institution - 0093
🇦🇺Woolloongabba, Queensland, Australia
Local Institution - 0078
🇫🇷Nimes, France
Local Institution
🇩🇪Lostau, Germany
Local Institution - 0058
🇦🇺Murdoch, Western Australia, Australia
Local Institution - 0054
🇦🇺Bedford Park, South Australia, Australia
Local Institution - 0146
🇨🇦Laval, Quebec, Canada
Local Institution - 0086
🇮🇹Localita San Filippo Lucca, Italy
Local Institution - 0061
🇩🇪Hamburg, Germany
Local Institution - 0087
🇮🇹Roma, Italy
Local Institution - 0113
🇩🇪Hannover, Germany
Local Institution - 0068
🇪🇸Las Palmas de Gran Canaria, Spain
Local Institution - 0046
🇺🇸Los Angeles, California, United States
MetroHealth Cancer Care Center
🇺🇸Cleveland, Ohio, United States
Local Institution - 0005
🇺🇸Pittsburgh, Pennsylvania, United States
Sharp Memorial Hospital
🇺🇸San Diego, California, United States
Local Institution - 0037
🇺🇸Cincinnati, Ohio, United States
Local Institution - 0132
🇺🇸Cincinnati, Ohio, United States
Local Institution - 0070
🇪🇸Sevilla, Spain
Local Institution - 0126
🇺🇸Orange, California, United States
CBCC Global Research, Inc.
🇺🇸Bakersfield, California, United States
Local Institution - 0142
🇺🇸Columbus, Georgia, United States
Local Institution - 0121
🇺🇸Marietta, Georgia, United States
Local Institution - 0098
🇺🇸Niles, Illinois, United States
Local Institution - 0100
🇺🇸Peoria, Illinois, United States
Local Institution - 0050
🇺🇸Fort Wayne, Indiana, United States
Innova Schar Cancer Institute
🇺🇸Falls Church, Virginia, United States
Local Institution - 0112
🇺🇸Paducah, Kentucky, United States
Local Institution - 0123
🇺🇸Wichita, Kansas, United States
Local Institution - 0125
🇺🇸Springfield, Massachusetts, United States
Local Institution - 0124
🇺🇸Sioux Falls, South Dakota, United States
Jones Clinic PC
🇺🇸Germantown, Tennessee, United States
Local Institution - 0022
🇺🇸Dallas, Texas, United States
Cancer Care Northwest
🇺🇸Spokane Valley, Washington, United States
Local Institution - 0052
🇦🇺St. Leonards, New South Wales, Australia
Local Institution - 0056
🇦🇺Elizabeth Vale, South Australia, Australia
Local Institution - 0057
🇦🇺Hobart, Tasmania, Australia
Local Institution - 0059
🇨🇦Newmarket, Ontario, Canada
Local Institution - 0060
🇨🇦St. Jerome, Quebec, Canada
Local Institution - 0080
🇫🇷Bayonne, France
Local Institution - 0105
🇫🇷Angers, France
Local Institution - 0076
🇫🇷Clermont-Ferrand Cedex 01, France
Local Institution - 0077
🇫🇷Le Mans, France
Local Institution - 0095
🇫🇷Paris, France
Local Institution - 0083
🇫🇷Paris, France
Local Institution - 0097
🇫🇷Vandoeuvre-les-Nancy, France
Local Institution - 0096
🇫🇷Villefranche-sur-Saone Cedex, France
Local Institution - 0102
🇩🇪Gauting, Germany
Local Institution - 0062
🇩🇪Greifenstein, Germany
Local Institution - 0106
🇩🇪Kiel, Germany
Local Institution - 0066
🇩🇪Moers, Germany
Local Institution - 0065
🇩🇪Leipzig, Germany
Local Institution - 0085
🇮🇹Monza, Italy
Local Institution - 0088
🇮🇹Napoli, Italy
Local Institution - 0069
🇪🇸Barcelona, Spain
Local Institution - 0104
🇪🇸El Palmar, Spain
Local Institution - 0067
🇩🇪Nürnberg, Germany
Ingalls Health System
🇺🇸Harvey, Illinois, United States
Local Institution - 0004
🇺🇸Birmingham, Alabama, United States
Local Institution - 0030
🇺🇸Phoenix, Arizona, United States
Local Institution - 0041
🇺🇸Phoenix, Arizona, United States
Local Institution - 0017
🇺🇸Denver, Colorado, United States
Local Institution - 0042
🇺🇸Bethesda, Maryland, United States
Local Institution - 0014
🇺🇸Omaha, Nebraska, United States
Local Institution - 0036
🇺🇸Nashville, Tennessee, United States
Local Institution - 0120
🇺🇸Minneapolis, Minnesota, United States
Local Institution - 0020
🇺🇸Charleston, South Carolina, United States