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A Study of Necitumumab Monotherapy and the QT/QTc Interval in Patient With Advanced Solid Tumors

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: NCT01624467
Recruitment Status : Completed
First Posted : June 20, 2012
Results First Posted : January 29, 2016
Last Update Posted : July 25, 2016
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Solid Tumors
Intervention Biological: Necitumumab
Enrollment 75
Recruitment Details  
Pre-assignment Details Completers are defined as the QTc complete participants who received full doses of necitumumab for ≥1 full 6-week cycle or did not complete the first cycle because of QTc prolongation, and had pretreatment and post-infusion triplicate ECGs at the times specified in all versions of the protocol.
Arm/Group Title Necitumumab
Hide Arm/Group Description 800 milligram (mg) necitumumab, administered once per week as an intravenous infusion (IV)
Period Title: Overall Study
Started 75
Received at Least One Dose of Study Drug 75
Completed 44
Not Completed 31
Reason Not Completed
Withdrawal by Subject             2
Lost to Follow-up             1
Adverse Event             7
Progressive Disease             19
Per Sponsor Requirement             1
Subject Withdrew from Treatment             1
Arm/Group Title Necitumumab
Hide Arm/Group Description 800 mg necitumumab, administered once per week IV
Overall Number of Baseline Participants 75
Hide Baseline Analysis Population Description
All QTc evaluable participants who received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 75 participants
60.3  (9.92)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 75 participants
Female
31
  41.3%
Male
44
  58.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 75 participants
Hispanic or Latino
3
   4.0%
Not Hispanic or Latino
72
  96.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 75 participants
American Indian or Alaska Native
1
   1.3%
Asian
1
   1.3%
Native Hawaiian or Other Pacific Islander
1
   1.3%
Black or African American
7
   9.3%
White
63
  84.0%
More than one race
1
   1.3%
Unknown or Not Reported
1
   1.3%
1.Primary Outcome
Title Change From Time-Matched Baseline in QT Interval Corrected for Heart Rate (QTc)
Hide Description The corrected QT interval was calculated using Fridericia's correction (QTcF) from electrocardiogram (ECG) data. Each participant had triplicate QT intervals measured at each timepoint and the average was calculated for each participant at each timepoint. For each timepoint, a participant's corresponding baseline (Day -1, pretreatment) QTcF interval was subtracted from the average QTcF intervals to create the change from time-matched baseline in the QTcF interval
Time Frame Baseline, Cycle1 Day 1, 8,15, 22, 29, and 36: Pre-infusion, End of Infusion, 1 Hour (hr), 2, 4, 24, 48, 72 hr Post Infusion
Hide Outcome Measure Data
Hide Analysis Population Description
QTC evaluable population: all participants who received at least 1 dose of study drug and at least 1 post-infusion ECG.
Arm/Group Title Necitumumab
Hide Arm/Group Description:
800 mg necitumumab, administered once per week IV
Overall Number of Participants Analyzed 75
Mean (90% Confidence Interval)
Unit of Measure: milliseconds (msec)
Cycle 1, Day 1(D1), Pre-Infusion (n=74)
1.00
(-0.44 to 2.44)
Cycle 1, D1, End of Infusion (n=75)
1.72
(0.17 to 3.28)
Cycle 1, D1, 1 hr Post-Infusion (n=75)
0.63
(-1.20 to 2.36)
Cycle 1,D1, 2 hr Post-Infusion (n=75)
-0.17
(-1.84 to 1.51)
Cycle 1,D1, 4 hr Post-Infusion (n=75)
-2.02
(-3.81 to -0.24)
Cycle 1,D1, 24 hr Post-Infusion (n=73)
-3.12
(-4.74 to -1.50)
Cycle 1,D1, 48 hr Post-Infusion (n=73)
-2.67
(-4.44 to -0.91)
Cycle 1,D1, 72 hr Post-Infusion (n=72)
-1.88
(-3.87 to 0.11)
Cycle 1, D8, Pre-Infusion (n=72)
5.19
(2.86 to 7.52)
Cycle 1, D8, End of Infusion (n=71)
8.20
(5.93 to 10.47)
Cycle 1 D8, 1 hr Post-Infusion (n=70)
5.34
(3.12 to 7.57)
Cycle 1, D8, 2 hr Post-Infusion (n=71)
4.41
(2.41 to 6.40)
Cycle 1, D8, 4 hr Post-Infusion (n=72)
3.42
(1.45 to 5.38)
Cycle 1, D15, Pre-Infusion (n=63)
4.92
(2.49 to 7.52)
Cycle 1, D15, End of Infusion (n=63)
6.47
(4.07 to 8.88)
Cycle 1, D15, 1 hr Post-Infusion (n=61)
5.07
(2.57 to 7.58)
Cycle 1, D15, 2 hr Post-Infusion (n=62)
4.04
(1.13 to 6.95)
Cycle 1, D15 4 hr Post-Infusion (n=62)
3.04
(0.44 to 5.63)
Cycle 1, D22, Pre-Infusion (n=61)
3.87
(1.79 to 5.96)
Cycle 1, D22, End of Infusion (n=59)
6.89
(4.47 to 9.31)
Cycle 1, D22, 1 hr Post-Infusion (n=59)
5.03
(2.56 to 7.50)
Cycle 1, D22, 2 hr Post-Infusion (n=60)
2.48
(0.27 to 4.69)
Cycle 1, D22 4 hr Post-Infusion (n-60)
1.53
(-0.66 to 3.72)
Cycle 1, D29, Pre-Infusion (n=59)
3.68
(1.38 to 5.98)
Cycle 1, D29, End of Infusion (n=59)
6.95
(4.74 to 9.16)
Cycle 1, D29, 1 hr Post-Infusion (n=59)
3.99
(1.54 to 6.44)
Cycle 1, D29, 2 hr Post-Infusion (n=59)
3.25
(1.01 to 5.48)
Cycle 1, D29, 4 hr Post-Infusion (n=59)
1.62
(-0.40 to 3.64)
Cycle 1, D36, Pre-Infusion (n=53)
4.47
(2.11 to 6.84)
Cycle 1, D36, End of Infusion (n=49)
5.14
(2.94 to 7.34)
Cycle 1, D36, 1 hr Post-Infusion (n=50)
3.59
(0.82 to 6.36)
Cycle 1, D36, 2 hr Post-Infusion (n-50)
2.77
(0.25 to 5.29)
Cycle 1, D36, 4 hr Post-Infusion (n=49)
1.15
(-1.11 to 3.40)
Cycle 1, D36, 24 hr Post-Infusion (n=49)
-0.64
(-2.83 to 1.55)
Cycle 1, D36, 48 hr Post-Infusion (n=50)
0.09
(-2.75 to 2.93)
Cycle 1, D36, 72 hr Post-Infusion (n=50)
-0.20
(-2.51 to 2.12)
2.Secondary Outcome
Title Change From Time-Matched Baseline ≥ 25% and Absolute Value of QRS >110 Msec (Electrocardiographic Parameters: QRS Interval)
Hide Description [Not Specified]
Time Frame Baseline, Cycle1 Day 1, 8, 15, 22, 29, 36: Pre-infusion, End of Infusion, 1 Hour (hr), 2, 4, 24, 48, 72 hr Post Infusion
Hide Outcome Measure Data
Hide Analysis Population Description
QTC evaluable population: all participants who received at least 1 dose of study drug and at least 1 post-infusion ECG
Arm/Group Title Necitumumab
Hide Arm/Group Description:
800 mg necitumumab, administered once per week IV
Overall Number of Participants Analyzed 75
Measure Type: Number
Unit of Measure: participants
0
3.Secondary Outcome
Title PR Change From Time-Matched Baseline ≥25% and Absolute Value of PR > 200 Msec (Electrocardiographic Parameters: PR Interval)
Hide Description [Not Specified]
Time Frame Baseline, Cycle1 Day 1, 8, 15, 22, 29, 36: Pre-infusion, End of Infusion, 1 Hour (hr), 2, 4, 24, 48, 72 hr Post Infusion
Hide Outcome Measure Data
Hide Analysis Population Description
QTC evaluable population: all participants who received at least 1 dose of study drug and at least 1 post-infusion ECG.
Arm/Group Title Necitumumab
Hide Arm/Group Description:
800 mg necitumumab, administered once per week IV
Overall Number of Participants Analyzed 75
Measure Type: Number
Unit of Measure: percentage of participants
0
4.Secondary Outcome
Title Change From Time-Matched Baseline in Heart Rate (HR) (Electrocardiographic Parameters: Heart Rate [HR])
Hide Description Change in HR from time-matched measures performed at baseline.
Time Frame Baseline, Cycle1 Day 36: Pre-infusion, End of Infusion, 1 Hour (hr), 2, 4, 24, 48, 72 hr Post Infusion
Hide Outcome Measure Data
Hide Analysis Population Description
QTC evaluable population: all participants who received at least 1 dose of study drug and at least 1 post-infusion ECG
Arm/Group Title Necitumumab
Hide Arm/Group Description:
800 mg necitumumab, administered once per week IV
Overall Number of Participants Analyzed 75
Mean (Standard Deviation)
Unit of Measure: Beats/minute
Cycle 1, D36, Pre-Infusion (n=53)) 0.50  (10.22)
Cycle 1, D36, End of Infusion, (n=49) 1.92  (12.44)
Cycle 1, D36, 1 hr Post-Infusion (n=50) 2.73  (12.21)
Cycle 1, D36, 2 hr Post-Infusion (n=50) 2.02  (11.77)
Cycle 1, D36, 4 hr Post-Infusion (n=49) 3.36  (8.39)
Cycle 1, D36, 24 hr Post-Infusion (n=49) 3.56  (10.05)
Cycle 1, D36, 48 hr Post-Infusion, (n=50) 5.09  (10.55)
Cycle 1, D36, 72 hr Post-Infusion (n=50) 4.86  (12.36)
Cycle 1, D36, 168 hr Post-Infusion (n=11) 10.75  (15.77)
5.Secondary Outcome
Title Pharmacokinetics (PK): Area Under the Concentration-Time Curve of Necitumumab From Zero to Infinity (AUC[0-∞])
Hide Description [Not Specified]
Time Frame Cycle1 (Days 1 and 36): Pre-infusion, 50 minutes, 1.5, 2.5, 4.5, 24, 28, 72, and 168 hours
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug and had evaluable PK parameters in Cycle 1 on Days 1 and 36.
Arm/Group Title Necitumumab: Cycle 1, Day 1 Necitumumab: Cycle 1, Day 36
Hide Arm/Group Description:
800 mg necitumumab, administered once per week IV
800 mg necitumumab, administered once per week IV
Overall Number of Participants Analyzed 18 11
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: microgram*hour/milliliter (μg*h/ml)
24500
(34%)
109000
(61%)
6.Secondary Outcome
Title Pharmacokinetics: Maximum Drug Concentration (Cmax) of Necitumumab
Hide Description [Not Specified]
Time Frame Cycle 1 (Days 1 and 36); Pre-infusion, 50 minutes, 1.5, 2.5, 4.5, 24, 28, 72, and 168 hours
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug and had evaluable PK parameters in Cycle 1, Days 1 and 36.
Arm/Group Title Necitumumab: Cycle 1, Day 1 Necitumumab: Cycle 1, Day 36
Hide Arm/Group Description:
800 mg necitumumab, administered once per week IV
800 mg necitumumab, administered once per week IV
Overall Number of Participants Analyzed 71 49
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: microgram/milliliter (μg/mL)
270
(27%)
470
(30%)
7.Secondary Outcome
Title Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) (Tumor Response Rate Per Response Evaluation Criteria in Solid Tumors Version 1.1 [RECIST 1.1])
Hide Description ORR is confirmed best overall tumor response of CR or PR. According to RECIST v1.1,CR was defined as the disappearance of all target and non-target lesions. Percentage of participants was calculated as: (total number of participants with CR or PR from start of the treatment until disease progression or recurrence)/total number of participants treated) * 100. PR defined as a >30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD.
Time Frame Baseline to Measured Progressive Disease (up to 21 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received any study drug and had CR or PR.
Arm/Group Title Necitumumab
Hide Arm/Group Description:
800 mg necitumumab, administered once per week IV
Overall Number of Participants Analyzed 75
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
2.7
(0.3 to 9.3)
8.Secondary Outcome
Title Number of Participants With an Incidence of Anti-Necitumumab Antibodies
Hide Description [Not Specified]
Time Frame Baseline to Post Infusion 30 Day Follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug and had at least 1 post-infusion blood sample.
Arm/Group Title Necitumumab
Hide Arm/Group Description:
800 mg necitumumab, administered once per week IV
Overall Number of Participants Analyzed 75
Measure Type: Number
Unit of Measure: participants
Overall Antibody Positive 9
Overall Treatment Emergent Antibody Positive 1
Time Frame [Not Specified]
Adverse Event Reporting Description All participants who received at least 1 dose of study drug.
 
Arm/Group Title Necitumumab
Hide Arm/Group Description 800 mg necitumumab, administered once per week as an intravenous infusion (IV)
All-Cause Mortality
Necitumumab
Affected / at Risk (%)
Total   --/--    
Hide Serious Adverse Events
Necitumumab
Affected / at Risk (%) # Events
Total   33/75 (44.00%)    
Blood and lymphatic system disorders   
Thrombocytopenia † 1  1/75 (1.33%)  1
Cardiac disorders   
Sinus tachycardia † 1  1/75 (1.33%)  1
Gastrointestinal disorders   
Abdominal pain † 1  1/75 (1.33%)  2
Ascites † 1  1/75 (1.33%)  1
Constipation † 1  1/75 (1.33%)  1
Epiploic appendagitis † 1  1/75 (1.33%)  1
Small intestinal obstruction † 1  4/75 (5.33%)  6
General disorders   
Asthenia † 1  1/75 (1.33%)  1
Disease recurrence † 1  1/75 (1.33%)  1
Non-cardiac chest pain † 1  1/75 (1.33%)  1
Hepatobiliary disorders   
Jaundice cholestatic † 1  1/75 (1.33%)  1
Immune system disorders   
Anaphylactic reaction † 1  1/75 (1.33%)  1
Drug hypersensitivity † 1  1/75 (1.33%)  1
Infections and infestations   
Clostridium difficile infection † 1  1/75 (1.33%)  1
Infection † 1  1/75 (1.33%)  2
Influenza † 1  1/75 (1.33%)  1
Klebsiella bacteraemia † 1  1/75 (1.33%)  1
Lung infection † 1  1/75 (1.33%)  1
Meningitis aseptic † 1  1/75 (1.33%)  1
Pneumonia † 1  1/75 (1.33%)  1
Sepsis † 1  1/75 (1.33%)  1
Urinary tract infection † 1  2/75 (2.67%)  2
Injury, poisoning and procedural complications   
Femur fracture † 1  1/75 (1.33%)  1
Infusion related reaction † 1  2/75 (2.67%)  2
Investigations   
Blood bilirubin increased † 1  1/75 (1.33%)  1
Lipase increased † 1  1/75 (1.33%)  1
Weight decreased † 1  1/75 (1.33%)  1
Metabolism and nutrition disorders   
Failure to thrive † 1  1/75 (1.33%)  1
Musculoskeletal and connective tissue disorders   
Flank pain † 1  1/75 (1.33%)  1
Osteolysis † 1  1/75 (1.33%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Malignant neoplasm progression † 1  6/75 (8.00%)  6
Malignant pleural effusion † 1  1/75 (1.33%)  1
Nervous system disorders   
Headache † 1  2/75 (2.67%)  2
Renal and urinary disorders   
Renal failure acute † 1  1/75 (1.33%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnoea † 1  3/75 (4.00%)  3
Pleural effusion † 1  1/75 (1.33%)  1
Pneumothorax † 1  1/75 (1.33%)  1
Pulmonary embolism † 1  4/75 (5.33%)  4
Vascular disorders   
Hypertension † 1  1/75 (1.33%)  1
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Necitumumab
Affected / at Risk (%) # Events
Total   75/75 (100.00%)    
Blood and lymphatic system disorders   
Anaemia † 1  29/75 (38.67%)  43
Cardiac disorders   
Sinus tachycardia † 1  4/75 (5.33%)  4
Eye disorders   
Vision blurred † 1  6/75 (8.00%)  7
Gastrointestinal disorders   
Abdominal pain † 1  7/75 (9.33%)  8
Constipation † 1  14/75 (18.67%)  15
Diarrhoea † 1  19/75 (25.33%)  32
Nausea † 1  32/75 (42.67%)  42
Stomatitis † 1  7/75 (9.33%)  8
Vomiting † 1  21/75 (28.00%)  25
General disorders   
Asthenia † 1  6/75 (8.00%)  6
Chills † 1  10/75 (13.33%)  11
Fatigue † 1  28/75 (37.33%)  33
Oedema peripheral † 1  7/75 (9.33%)  8
Pyrexia † 1  14/75 (18.67%)  16
Infections and infestations   
Urinary tract infection † 1  6/75 (8.00%)  7
Injury, poisoning and procedural complications   
Infusion related reaction † 1  6/75 (8.00%)  12
Investigations   
Activated partial thromboplastin time prolonged † 1  4/75 (5.33%)  9
Alanine aminotransferase increased † 1  7/75 (9.33%)  8
Aspartate aminotransferase increased † 1  14/75 (18.67%)  15
Blood alkaline phosphatase increased † 1  14/75 (18.67%)  19
Blood bilirubin increased † 1  4/75 (5.33%)  4
Blood creatinine increased † 1  8/75 (10.67%)  13
Electrocardiogram qt prolonged † 1  26/75 (34.67%)  61
International normalised ratio increased † 1  4/75 (5.33%)  5
Lymphocyte count decreased † 1  21/75 (28.00%)  59
Weight decreased † 1  7/75 (9.33%)  9
Metabolism and nutrition disorders   
Decreased appetite † 1  21/75 (28.00%)  22
Dehydration † 1  5/75 (6.67%)  7
Hyperglycaemia † 1  14/75 (18.67%)  44
Hyperkalaemia † 1  7/75 (9.33%)  8
Hypoalbuminaemia † 1  21/75 (28.00%)  34
Hypocalcaemia † 1  6/75 (8.00%)  6
Hypokalaemia † 1  18/75 (24.00%)  22
Hypomagnesaemia † 1  26/75 (34.67%)  55
Hyponatraemia † 1  7/75 (9.33%)  7
Musculoskeletal and connective tissue disorders   
Arthralgia † 1  7/75 (9.33%)  7
Back pain † 1  9/75 (12.00%)  10
Muscle spasms † 1  4/75 (5.33%)  4
Musculoskeletal pain † 1  4/75 (5.33%)  4
Pain in extremity † 1  6/75 (8.00%)  7
Nervous system disorders   
Dizziness † 1  11/75 (14.67%)  11
Dysgeusia † 1  5/75 (6.67%)  9
Headache † 1  44/75 (58.67%)  55
Neuropathy peripheral † 1  4/75 (5.33%)  6
Psychiatric disorders   
Anxiety † 1  8/75 (10.67%)  10
Insomnia † 1  9/75 (12.00%)  11
Respiratory, thoracic and mediastinal disorders   
Cough † 1  12/75 (16.00%)  14
Dyspnoea † 1  8/75 (10.67%)  8
Epistaxis † 1  5/75 (6.67%)  5
Nasal congestion † 1  8/75 (10.67%)  8
Oropharyngeal pain † 1  6/75 (8.00%)  7
Skin and subcutaneous tissue disorders   
Dermatitis acneiform † 1  25/75 (33.33%)  32
Dry skin † 1  17/75 (22.67%)  20
Palmar-plantar erythrodysaesthesia syndrome † 1  9/75 (12.00%)  12
Pruritus † 1  11/75 (14.67%)  11
Rash † 1  31/75 (41.33%)  48
Rash maculo-papular † 1  7/75 (9.33%)  8
Skin fissures † 1  6/75 (8.00%)  7
Vascular disorders   
Flushing † 1  5/75 (6.67%)  5
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
[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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01624467    
Other Study ID Numbers: 14472
CP11-1114 ( Other Identifier: ImClone Systems )
I4X-IE-JFCI ( Other Identifier: Eli Lilly and Company )
First Submitted: May 24, 2012
First Posted: June 20, 2012
Results First Submitted: December 21, 2015
Results First Posted: January 29, 2016
Last Update Posted: July 25, 2016