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Trial of Nivolumab vs Therapy of Investigator's Choice in Recurrent or Metastatic Head and Neck Carcinoma (CheckMate 141)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02105636
Recruitment Status : Active, not recruiting
First Posted : April 7, 2014
Results First Posted : January 11, 2017
Last Update Posted : October 1, 2019
Sponsor:
Collaborator:
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Squamous Cell Carcinoma of the Head and Neck
Interventions Drug: Nivolumab
Drug: Cetuximab
Drug: Methotrexate
Drug: Docetaxel
Enrollment 506
Recruitment Details 506 enrolled, 361 randomized. Non-randomized reasons: 5 adverse events, 18 withdrew consent, 7 died, 108 no longer met study criteria, 7 other. 347 treated (236 nivo, 111 IC). Non-treatment reasons: 1 disease progression, 3 request to discontinue treatment, 6 withdrew consent, 4 no longer met study criteria. Nivo=nivolumab, IC=investigator's choice
Pre-assignment Details  
Arm/Group Title Nivolumab 3mg/kg Cetuximab/Methotrexate/Docetaxel
Hide Arm/Group Description Nivolumab was provided at a dose of 3 milligrams/kilogram (mg/kg) using an intravenous (IV) solution for Injection every 2 weeks until disease progression. Participants were provided a dose of Cetuximab intravenous (IV) solution for injection at a dose of 400 milligram/meter squared (mg/m2) for the first dose followed that a doses of 250 mg/m2 weekly until disease progression OR a Methotrexate intravenous (IV) solution for Injection at a dose of 40 or 60 mg/m2 weekly until disease progression OR a Docetaxel intravenous (IV) solution for Injection at a dose of 30 or 40 mg/m2 weekly until disease progression. The decision regarding which treatment the participant received was at the discretion of the investigator and referred to as Investigators Choice.
Period Title: Overall Study
Started 236 111
Completed 41 [1] 3 [1]
Not Completed 195 108
Reason Not Completed
Disease Progression             162             83
Study Drug Toxicity             9             11
Adverse Event Unrelated to Study Drug             12             3
Subject Request to Discontinue Treatment             4             6
Subject Withdrew Consent             4             1
Maximum Clinical Benefit             1             1
Poor/Non-compliance             0             1
Reason Not Specified             0             2
Not Reported             3             0
[1]
Completed=Still on Treatment
Arm/Group Title Nivolumab 3mg/kg Cetuximab/Methotrexate/Docetaxel Total
Hide Arm/Group Description Nivolumab was provided at a dose of 3 milligrams/kilogram (mg/kg) using an intravenous (IV) solution for Injection every 2 weeks until disease progression. Participants were provided a dose of Cetuximab intravenous (IV) solution for injection at a dose of 400 milligram/meter squared (mg/m2) for the first dose followed that a doses of 250 mg/m2 weekly until disease progression OR a Methotrexate intravenous (IV) solution for Injection at a dose of 40 or 60 mg/m2 weekly until disease progression OR a Docetaxel intravenous (IV) solution for Injection at a dose of 30 or 40 mg/m2 weekly until disease progression. The decision regarding which treatment the participant received was at the discretion of the investigator and referred to as Investigators Choice. Total of all reporting groups
Overall Number of Baseline Participants 240 121 361
Hide Baseline Analysis Population Description
All Randomized Participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 240 participants 121 participants 361 participants
59.0  (10.15) 59.4  (11.00) 59.1  (10.43)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 240 participants 121 participants 361 participants
< 65 years 172 76 248
>=65 and <75 years 56 39 95
>=75 years 12 6 18
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 240 participants 121 participants 361 participants
Female
43
  17.9%
18
  14.9%
61
  16.9%
Male
197
  82.1%
103
  85.1%
300
  83.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 240 participants 121 participants 361 participants
White 196 104 300
Black or African American 10 3 13
Asian 29 14 43
Other 5 0 5
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 240 participants 121 participants 361 participants
Hispanic/Latino 9 4 13
Not Hispanic/Latino 132 60 192
Not Reported 99 57 156
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 240 participants 121 participants 361 participants
0 49 23 72
1 189 94 283
>=2 1 3 4
Not Reported 1 1 2
[1]
Measure Description: ECOG is a 6-item scale used to assess disease progression, daily functioning, appropriate treatment, and prognosis. Performance status is scored on a scale ranging from 0-5, with (best score) 0=fully active and able to carry on all pre-disease performance without restriction and (worst score) 5=death.
1.Primary Outcome
Title Overall Survival (OS) Time in Months for All Randomized Participants at Primary Endpoint
Hide Description Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. Median OS time was calculated using Kaplan-Meier (KM) method. Hazard ratio (HR) and the corresponding Confidence Interval (CI) were estimated in a stratified Cox proportional hazards model for distribution of OS in each randomized arm. Interim analysis (Primary Endpoint) occurred at 218 deaths.
Time Frame From date of randomization to date of death, approximately 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title Nivolumab 3mg/kg Cetuximab/Methotrexate/Docetaxel
Hide Arm/Group Description:
Nivolumab was provided at a dose of 3 milligrams/kilogram (mg/kg) using an intravenous (IV) solution for Injection every 2 weeks until disease progression.
Participants were provided a dose of Cetuximab intravenous (IV) solution for injection at a dose of 400 milligram/meter squared (mg/m2) for the first dose followed that a doses of 250 mg/m2 weekly until disease progression OR a Methotrexate intravenous (IV) solution for Injection at a dose of 40 or 60 mg/m2 weekly until disease progression OR a Docetaxel intravenous (IV) solution for Injection at a dose of 30 or 40 mg/m2 weekly until disease progression. The decision regarding which treatment the participant received was at the discretion of the investigator and referred to as Investigators Choice.
Overall Number of Participants Analyzed 240 121
Median (95% Confidence Interval)
Unit of Measure: months
7.49
(5.49 to 9.10)
5.06
(4.04 to 6.05)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nivolumab 3mg/kg, Cetuximab/Methotrexate/Docetaxel
Comments Stratified Cox proportional hazard model. HR = Nivolumab over investigator's choice therapy (Cetuximab, Methotrexate, or Docetaxel)
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0101
Comments Log-rank Test stratified by prior treatment with cetuximab (yes, no) as entered into the Interactive Voice Response System (IVRS). For OS the boundary for statistical significance requires the p-value to be less than 0.0227.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
0.53 to 0.92
Estimation Comments [Not Specified]
2.Primary Outcome
Title Overall Survival (OS) Rate in All Randomized Participants at Primary Endpoint
Hide Description The overall survival rate is the probability that a participant will be alive at 3, 6, 9, and 12 months following randomization. Overall survival was defined as the time between the date of randomization and the date of death as a result of any cause. Survival rates were determined via Kaplan-Meier estimates.
Time Frame Randomization to 3, 6, 9, and 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Nivolumab 3mg/kg Cetuximab/Methotrexate/Docetaxel
Hide Arm/Group Description:
Nivolumab was provided at a dose of 3 milligrams/kilogram (mg/kg) using an intravenous (IV) solution for Injection every 2 weeks until disease progression.
Participants were provided a dose of Cetuximab intravenous (IV) solution for injection at a dose of 400 milligram/meter squared (mg/m2) for the first dose followed that a doses of 250 mg/m2 weekly until disease progression OR a Methotrexate intravenous (IV) solution for Injection at a dose of 40 or 60 mg/m2 weekly until disease progression OR a Docetaxel intravenous (IV) solution for Injection at a dose of 30 or 40 mg/m2 weekly until disease progression. The decision regarding which treatment the participant received was at the discretion of the investigator and referred to as Investigators Choice.
Overall Number of Participants Analyzed 240 121
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percent probability of OS
3 months
71.5
(65.3 to 76.8)
74.0
(65.1 to 81.0)
6 months
55.6
(48.9 to 61.8)
41.8
(32.6 to 50.7)
9 months
43.4
(36.2 to 50.3)
29.1
(20.3 to 38.5)
12 months
36.0
(28.5 to 43.4)
16.6
(8.6 to 26.8)
3.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide Description PFS was defined as the time between the date of randomization and the first date of documented progression, as determined by the investigator (as per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria), or death due to any cause, whichever occurs first. Participants who die without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants without any on study tumor assessments and did not die were censored on their date of randomization. Participants who received subsequent systemic anti-cancer therapy prior to documented progression were censored at the date of the last tumor assessment prior to the initiation of the new therapy.
Time Frame Randomization to disease progression or death, whichever occurs first; Approximately 5 years
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description ORR was defined as the proportion of randomized participants who achieved a best response of complete response (CR) or partial response (PR) using the RECIST1.1 criteria as per investigator assessment. Best overall response (BOR) was defined as the best response designation, recorded between the date of randomization and the date of progression, as assessed by the investigator per RECIST 1.1 or the date of subsequent anticancer therapy (including tumor-directed radiotherapy and tumor-directed surgery), whichever occurs first. For participants without evidence of RECIST 1.1 progression or subsequent anticancer therapy, all available response assessments will contribute to the BOR assessment. For participants who continue treatment beyond progression, the BOR was determined based on response assessments up to the time of initial RECIST 1.1 progression.
Time Frame Randomization to disease progression or study drug is discontinued, whichever occurs first; Approximately 5 years
Outcome Measure Data Not Reported
5.Other Pre-specified Outcome
Title Number of Participants With Death, Study Drug-Related Death, Serious Adverse Events (SAEs), and Study Drug-Related SAEs in All Treated Participants at Primary Endpoint
Hide Description AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug.
Time Frame Date of first dose of study drug to 30 days post last dose of study drug, approximately 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Participants: All randomized participants who received at least one dose of study drug
Arm/Group Title Nivolumab 3mg/kg Cetuximab/Methotrexate/Docetaxel
Hide Arm/Group Description:
Nivolumab was provided at a dose of 3 milligrams/kilogram (mg/kg) using an intravenous (IV) solution for Injection every 2 weeks until disease progression.
Participants were provided a dose of Cetuximab intravenous (IV) solution for injection at a dose of 400 milligram/meter squared (mg/m2) for the first dose followed that a doses of 250 mg/m2 weekly until disease progression OR a Methotrexate intravenous (IV) solution for Injection at a dose of 40 or 60 mg/m2 weekly until disease progression OR a Docetaxel intravenous (IV) solution for Injection at a dose of 30 or 40 mg/m2 weekly until disease progression. The decision regarding which treatment the participant received was at the discretion of the investigator and referred to as Investigator's Choice.
Overall Number of Participants Analyzed 236 111
Measure Type: Number
Unit of Measure: participants
Deaths 50 21
Study Drug-Related Deaths 2 0
SAEs 127 66
Study Drug-Related SAEs 16 17
AEs Leading to Discontinuation 51 27
Study Drug-Related AEs Leading to Discontinuation 9 11
Time Frame From first dose to last dose plus 30 days up to Primary Endpoint, approximately 18 months (November 2015)
Adverse Event Reporting Description Study initiated: May 2014; Primary Endpoint: November 2015 (study on-going)
 
Arm/Group Title Nivolumab 3 mg/kg Cetuximab/Methotrexate/Docetaxel
Hide Arm/Group Description Nivolumab was provided at a dose of 3 milligrams/kilogram (mg/kg) using an intravenous (IV) solution for Injection every 2 weeks until disease progression. Participants were provided a dose of Cetuximab intravenous (IV) solution for injection at a dose of 400 milligram/meter squared (mg/m2) for the first dose followed that a doses of 250 mg/m2 weekly until disease progression OR a Methotrexate intravenous (IV) solution for Injection at a dose of 40 or 60 mg/m2 weekly until disease progression OR a Docetaxel intravenous (IV) solution for Injection at a dose of 30 or 40 mg/m2 weekly until disease progression. The decision regarding which treatment the participant received was at the discretion of the investigator and referred to as Investigators Choice.
All-Cause Mortality
Nivolumab 3 mg/kg Cetuximab/Methotrexate/Docetaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Nivolumab 3 mg/kg Cetuximab/Methotrexate/Docetaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   127/236 (53.81%)   66/111 (59.46%) 
Blood and lymphatic system disorders     
Anaemia † 1  0/236 (0.00%)  2/111 (1.80%) 
Leukopenia † 1  0/236 (0.00%)  1/111 (0.90%) 
Cardiac disorders     
Acute myocardial infarction † 1  1/236 (0.42%)  0/111 (0.00%) 
Atrial flutter † 1  1/236 (0.42%)  1/111 (0.90%) 
Cardiac arrest † 1  0/236 (0.00%)  1/111 (0.90%) 
Cardiac failure † 1  2/236 (0.85%)  0/111 (0.00%) 
Cardio-respiratory arrest † 1  1/236 (0.42%)  0/111 (0.00%) 
Atrial fibrillation † 1  0/236 (0.00%)  1/111 (0.90%) 
Pericarditis † 1  1/236 (0.42%)  0/111 (0.00%) 
Cardiovascular disorder † 1  0/236 (0.00%)  1/111 (0.90%) 
Supraventricular tachycardia † 1  0/236 (0.00%)  1/111 (0.90%) 
Cardiopulmonary failure † 1  1/236 (0.42%)  0/111 (0.00%) 
Congenital, familial and genetic disorders     
Tracheo-oesophageal fistula † 1  0/236 (0.00%)  1/111 (0.90%) 
Ear and labyrinth disorders     
Vertigo † 1  0/236 (0.00%)  1/111 (0.90%) 
Endocrine disorders     
Hypophysitis † 1  1/236 (0.42%)  0/111 (0.00%) 
Secondary hypothyroidism † 1  1/236 (0.42%)  0/111 (0.00%) 
Secondary adrenocortical insufficiency † 1  1/236 (0.42%)  0/111 (0.00%) 
Eye disorders     
Visual acuity reduced † 1  0/236 (0.00%)  1/111 (0.90%) 
Blindness unilateral † 1  1/236 (0.42%)  0/111 (0.00%) 
Gastrointestinal disorders     
Abdominal pain † 1  1/236 (0.42%)  2/111 (1.80%) 
Colitis † 1  0/236 (0.00%)  1/111 (0.90%) 
Gastric haemorrhage † 1  1/236 (0.42%)  0/111 (0.00%) 
Gastritis † 1  0/236 (0.00%)  1/111 (0.90%) 
Gastric disorder † 1  1/236 (0.42%)  0/111 (0.00%) 
Nausea † 1  0/236 (0.00%)  1/111 (0.90%) 
Pneumoperitoneum † 1  1/236 (0.42%)  0/111 (0.00%) 
Stomatitis † 1  1/236 (0.42%)  1/111 (0.90%) 
Tongue haemorrhage † 1  2/236 (0.85%)  0/111 (0.00%) 
Parotid gland haemorrhage † 1  1/236 (0.42%)  0/111 (0.00%) 
Diarrhoea † 1  0/236 (0.00%)  2/111 (1.80%) 
Oesophageal stenosis † 1  1/236 (0.42%)  0/111 (0.00%) 
Dysphagia † 1  2/236 (0.85%)  3/111 (2.70%) 
General disorders     
Face oedema † 1  0/236 (0.00%)  1/111 (0.90%) 
Asthenia † 1  1/236 (0.42%)  2/111 (1.80%) 
Pyrexia † 1  3/236 (1.27%)  4/111 (3.60%) 
Mucosal inflammation † 1  0/236 (0.00%)  1/111 (0.90%) 
Pain † 1  0/236 (0.00%)  1/111 (0.90%) 
General physical health deterioration † 1  0/236 (0.00%)  1/111 (0.90%) 
Catheter site pain † 1  1/236 (0.42%)  0/111 (0.00%) 
Localised oedema † 1  1/236 (0.42%)  0/111 (0.00%) 
Malaise † 1  0/236 (0.00%)  2/111 (1.80%) 
Ulcer haemorrhage † 1  1/236 (0.42%)  0/111 (0.00%) 
Disease progression † 1  1/236 (0.42%)  0/111 (0.00%) 
Drug intolerance † 1  0/236 (0.00%)  1/111 (0.90%) 
Chills † 1  1/236 (0.42%)  1/111 (0.90%) 
Device occlusion † 1  0/236 (0.00%)  1/111 (0.90%) 
Fatigue † 1  2/236 (0.85%)  1/111 (0.90%) 
Immune system disorders     
Allergic granulomatous angiitis † 1  1/236 (0.42%)  0/111 (0.00%) 
Infections and infestations     
Infection † 1  2/236 (0.85%)  0/111 (0.00%) 
Respiratory tract infection † 1  5/236 (2.12%)  1/111 (0.90%) 
Skin infection † 1  0/236 (0.00%)  1/111 (0.90%) 
Lower respiratory tract infection † 1  3/236 (1.27%)  3/111 (2.70%) 
Peritonitis † 1  1/236 (0.42%)  0/111 (0.00%) 
Pneumonia bacterial † 1  1/236 (0.42%)  0/111 (0.00%) 
Lymphangitis † 1  1/236 (0.42%)  0/111 (0.00%) 
Otitis media † 1  1/236 (0.42%)  0/111 (0.00%) 
Upper respiratory tract infection † 1  0/236 (0.00%)  1/111 (0.90%) 
Tracheitis † 1  1/236 (0.42%)  0/111 (0.00%) 
Urinary tract infection † 1  4/236 (1.69%)  0/111 (0.00%) 
Cellulitis † 1  0/236 (0.00%)  1/111 (0.90%) 
Gastrointestinal infection † 1  0/236 (0.00%)  1/111 (0.90%) 
Neutropenic sepsis † 1  1/236 (0.42%)  1/111 (0.90%) 
Purulent discharge † 1  1/236 (0.42%)  0/111 (0.00%) 
Clostridium difficile colitis † 1  1/236 (0.42%)  1/111 (0.90%) 
Pneumonia † 1  10/236 (4.24%)  1/111 (0.90%) 
Sepsis † 1  5/236 (2.12%)  3/111 (2.70%) 
Device related infection † 1  0/236 (0.00%)  2/111 (1.80%) 
Localised infection † 1  1/236 (0.42%)  1/111 (0.90%) 
Lung infection † 1  4/236 (1.69%)  4/111 (3.60%) 
Wound infection † 1  1/236 (0.42%)  1/111 (0.90%) 
Injury, poisoning and procedural complications     
Wound haemorrhage † 1  1/236 (0.42%)  0/111 (0.00%) 
Post procedural haemorrhage † 1  1/236 (0.42%)  1/111 (0.90%) 
Tracheostomy malfunction † 1  1/236 (0.42%)  0/111 (0.00%) 
Vascular pseudoaneurysm ruptured † 1  1/236 (0.42%)  0/111 (0.00%) 
Infusion related reaction † 1  1/236 (0.42%)  1/111 (0.90%) 
Investigations     
Blood alkaline phosphatase increased † 1  1/236 (0.42%)  0/111 (0.00%) 
Blood bilirubin increased † 1  1/236 (0.42%)  0/111 (0.00%) 
Liver function test abnormal † 1  1/236 (0.42%)  0/111 (0.00%) 
Platelet count decreased † 1  0/236 (0.00%)  1/111 (0.90%) 
Transaminases increased † 1  1/236 (0.42%)  0/111 (0.00%) 
Metabolism and nutrition disorders     
Hypernatraemia † 1  0/236 (0.00%)  1/111 (0.90%) 
Malnutrition † 1  2/236 (0.85%)  0/111 (0.00%) 
Hyponatraemia † 1  2/236 (0.85%)  0/111 (0.00%) 
Hypophagia † 1  1/236 (0.42%)  0/111 (0.00%) 
Decreased appetite † 1  4/236 (1.69%)  1/111 (0.90%) 
Dehydration † 1  3/236 (1.27%)  0/111 (0.00%) 
Hyperglycaemia † 1  1/236 (0.42%)  0/111 (0.00%) 
Hypophosphataemia † 1  1/236 (0.42%)  0/111 (0.00%) 
Hypercalcaemia † 1  3/236 (1.27%)  1/111 (0.90%) 
Musculoskeletal and connective tissue disorders     
Back pain † 1  2/236 (0.85%)  0/111 (0.00%) 
Bone pain † 1  1/236 (0.42%)  0/111 (0.00%) 
Musculoskeletal chest pain † 1  1/236 (0.42%)  0/111 (0.00%) 
Pain in extremity † 1  1/236 (0.42%)  0/111 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tumour haemorrhage † 1  2/236 (0.85%)  0/111 (0.00%) 
Cancer pain † 1  1/236 (0.42%)  0/111 (0.00%) 
Head and neck cancer † 1  1/236 (0.42%)  0/111 (0.00%) 
Tumour pain † 1  0/236 (0.00%)  1/111 (0.90%) 
Malignant pleural effusion † 1  1/236 (0.42%)  0/111 (0.00%) 
Neoplasm malignant † 1  1/236 (0.42%)  0/111 (0.00%) 
Metastases to central nervous system † 1  1/236 (0.42%)  0/111 (0.00%) 
Malignant neoplasm progression † 1  43/236 (18.22%)  25/111 (22.52%) 
Nervous system disorders     
Cerebrovascular accident † 1  1/236 (0.42%)  0/111 (0.00%) 
Headache † 1  0/236 (0.00%)  1/111 (0.90%) 
Neuralgia † 1  0/236 (0.00%)  1/111 (0.90%) 
Syncope † 1  1/236 (0.42%)  1/111 (0.90%) 
Hydrocephalus † 1  1/236 (0.42%)  0/111 (0.00%) 
Speech disorder † 1  1/236 (0.42%)  0/111 (0.00%) 
Dizziness † 1  0/236 (0.00%)  2/111 (1.80%) 
Encephalopathy † 1  1/236 (0.42%)  0/111 (0.00%) 
Ischaemic stroke † 1  1/236 (0.42%)  0/111 (0.00%) 
Complex partial seizures † 1  1/236 (0.42%)  0/111 (0.00%) 
Psychiatric disorders     
Delirium † 1  1/236 (0.42%)  0/111 (0.00%) 
Agoraphobia † 1  0/236 (0.00%)  1/111 (0.90%) 
Renal and urinary disorders     
Acute kidney injury † 1  0/236 (0.00%)  1/111 (0.90%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure † 1  1/236 (0.42%)  0/111 (0.00%) 
Dyspnoea † 1  9/236 (3.81%)  1/111 (0.90%) 
Laryngeal stenosis † 1  1/236 (0.42%)  0/111 (0.00%) 
Obstructive airways disorder † 1  1/236 (0.42%)  0/111 (0.00%) 
Hypoxia † 1  0/236 (0.00%)  1/111 (0.90%) 
Bronchopneumopathy † 1  0/236 (0.00%)  1/111 (0.90%) 
Pneumothorax † 1  1/236 (0.42%)  0/111 (0.00%) 
Pneumothorax spontaneous † 1  1/236 (0.42%)  0/111 (0.00%) 
Pharyngeal oedema † 1  1/236 (0.42%)  0/111 (0.00%) 
Respiratory distress † 1  1/236 (0.42%)  2/111 (1.80%) 
Haemoptysis † 1  2/236 (0.85%)  1/111 (0.90%) 
Pneumonia aspiration † 1  8/236 (3.39%)  2/111 (1.80%) 
Laryngeal oedema † 1  1/236 (0.42%)  1/111 (0.90%) 
Pleural effusion † 1  2/236 (0.85%)  3/111 (2.70%) 
Stridor † 1  2/236 (0.85%)  0/111 (0.00%) 
Pneumonitis † 1  2/236 (0.85%)  0/111 (0.00%) 
Respiratory failure † 1  4/236 (1.69%)  0/111 (0.00%) 
Skin and subcutaneous tissue disorders     
Dermatomyositis † 1  0/236 (0.00%)  1/111 (0.90%) 
Angioedema † 1  0/236 (0.00%)  1/111 (0.90%) 
Skin mass † 1  1/236 (0.42%)  0/111 (0.00%) 
Skin ulcer † 1  1/236 (0.42%)  0/111 (0.00%) 
Vascular disorders     
Haematoma † 1  0/236 (0.00%)  1/111 (0.90%) 
Hypertensive crisis † 1  1/236 (0.42%)  0/111 (0.00%) 
Superior vena cava syndrome † 1  1/236 (0.42%)  0/111 (0.00%) 
Hypovolaemic shock † 1  0/236 (0.00%)  1/111 (0.90%) 
Shock haemorrhagic † 1  1/236 (0.42%)  0/111 (0.00%) 
Haemorrhage † 1  1/236 (0.42%)  0/111 (0.00%) 
Hypotension † 1  0/236 (0.00%)  1/111 (0.90%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Nivolumab 3 mg/kg Cetuximab/Methotrexate/Docetaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   202/236 (85.59%)   105/111 (94.59%) 
Blood and lymphatic system disorders     
Thrombocytopenia † 1  3/236 (1.27%)  6/111 (5.41%) 
Neutropenia † 1  1/236 (0.42%)  9/111 (8.11%) 
Anaemia † 1  44/236 (18.64%)  36/111 (32.43%) 
Cardiac disorders     
Tachycardia † 1  3/236 (1.27%)  6/111 (5.41%) 
Endocrine disorders     
Hypothyroidism † 1  15/236 (6.36%)  6/111 (5.41%) 
Eye disorders     
Lacrimation increased † 1  1/236 (0.42%)  6/111 (5.41%) 
Gastrointestinal disorders     
Gastrooesophageal reflux disease † 1  2/236 (0.85%)  8/111 (7.21%) 
Constipation † 1  36/236 (15.25%)  20/111 (18.02%) 
Nausea † 1  45/236 (19.07%)  34/111 (30.63%) 
Stomatitis † 1  7/236 (2.97%)  11/111 (9.91%) 
Vomiting † 1  27/236 (11.44%)  14/111 (12.61%) 
Dry mouth † 1  7/236 (2.97%)  6/111 (5.41%) 
Diarrhoea † 1  35/236 (14.83%)  25/111 (22.52%) 
Dysphagia † 1  28/236 (11.86%)  13/111 (11.71%) 
General disorders     
Face oedema † 1  10/236 (4.24%)  8/111 (7.21%) 
Oedema peripheral † 1  18/236 (7.63%)  5/111 (4.50%) 
Asthenia † 1  24/236 (10.17%)  23/111 (20.72%) 
Pyrexia † 1  29/236 (12.29%)  12/111 (10.81%) 
Mucosal inflammation † 1  8/236 (3.39%)  17/111 (15.32%) 
Fatigue † 1  62/236 (26.27%)  35/111 (31.53%) 
Infections and infestations     
Respiratory tract infection † 1  4/236 (1.69%)  6/111 (5.41%) 
Oral candidiasis † 1  6/236 (2.54%)  6/111 (5.41%) 
Investigations     
Aspartate aminotransferase increased † 1  12/236 (5.08%)  4/111 (3.60%) 
Blood alkaline phosphatase increased † 1  17/236 (7.20%)  3/111 (2.70%) 
Weight decreased † 1  31/236 (13.14%)  16/111 (14.41%) 
Metabolism and nutrition disorders     
Hyponatraemia † 1  21/236 (8.90%)  14/111 (12.61%) 
Decreased appetite † 1  41/236 (17.37%)  21/111 (18.92%) 
Hyperglycaemia † 1  12/236 (5.08%)  9/111 (8.11%) 
Hypercalcaemia † 1  15/236 (6.36%)  7/111 (6.31%) 
Hypokalaemia † 1  8/236 (3.39%)  8/111 (7.21%) 
Musculoskeletal and connective tissue disorders     
Back pain † 1  12/236 (5.08%)  0/111 (0.00%) 
Neck pain † 1  12/236 (5.08%)  8/111 (7.21%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tumour pain † 1  13/236 (5.51%)  6/111 (5.41%) 
Nervous system disorders     
Headache † 1  21/236 (8.90%)  3/111 (2.70%) 
Neuropathy peripheral † 1  4/236 (1.69%)  8/111 (7.21%) 
Psychiatric disorders     
Insomnia † 1  12/236 (5.08%)  7/111 (6.31%) 
Anxiety † 1  8/236 (3.39%)  7/111 (6.31%) 
Respiratory, thoracic and mediastinal disorders     
Cough † 1  32/236 (13.56%)  10/111 (9.01%) 
Dyspnoea † 1  27/236 (11.44%)  11/111 (9.91%) 
Productive cough † 1  12/236 (5.08%)  2/111 (1.80%) 
Epistaxis † 1  4/236 (1.69%)  11/111 (9.91%) 
Pleural effusion † 1  5/236 (2.12%)  6/111 (5.41%) 
Skin and subcutaneous tissue disorders     
Rash † 1  20/236 (8.47%)  5/111 (4.50%) 
Pruritus † 1  20/236 (8.47%)  0/111 (0.00%) 
Dry skin † 1  11/236 (4.66%)  12/111 (10.81%) 
Erythema † 1  3/236 (1.27%)  6/111 (5.41%) 
Alopecia † 1  2/236 (0.85%)  14/111 (12.61%) 
Vascular disorders     
Hypertension † 1  14/236 (5.93%)  3/111 (2.70%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
EMail: Clinical.Trials@bms.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02105636    
Other Study ID Numbers: CA209-141
2013-003622-86 ( EudraCT Number )
First Submitted: April 3, 2014
First Posted: April 7, 2014
Results First Submitted: November 15, 2016
Results First Posted: January 11, 2017
Last Update Posted: October 1, 2019