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A Study in Non-Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT01232452
Recruitment Status : Completed
First Posted : November 2, 2010
Results First Posted : June 12, 2018
Last Update Posted : September 20, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non-Small-Cell Lung Carcinoma
Interventions Drug: Pemetrexed
Drug: Cisplatin
Drug: Cixutumumab
Enrollment 172
Recruitment Details  
Pre-assignment Details Completers are those participants who died or had progressive disease (PD).
Arm/Group Title Pemetrexed + Cisplatin + Cixutumumab Pemetrexed + Cisplatin
Hide Arm/Group Description

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 plus cixutumumab 20 mg/kg given intravenously (IV) on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Period Title: Overall Study
Started 87 85
Received at Least One Dose of Study Drug 85 81
Completed 48 46
Not Completed 39 39
Reason Not Completed
Adverse Event             17             15
Withdrawal by Subject             11             8
Physician Decision             8             12
Protocol entry criterion not met             0             2
Sponsor Decision             3             1
Protocol Violation             0             1
Arm/Group Title Pemetrexed + Cisplatin + Cixutumumab Pemetrexed + Cisplatin Total
Hide Arm/Group Description

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Total of all reporting groups
Overall Number of Baseline Participants 87 85 172
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 87 participants 85 participants 172 participants
59.5  (9.87) 59.3  (9.96) 59.4  (9.89)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 87 participants 85 participants 172 participants
Female
33
  37.9%
32
  37.6%
65
  37.8%
Male
54
  62.1%
53
  62.4%
107
  62.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 87 participants 85 participants 172 participants
Hispanic or Latino
13
  14.9%
24
  28.2%
37
  21.5%
Not Hispanic or Latino
45
  51.7%
33
  38.8%
78
  45.3%
Unknown or Not Reported
29
  33.3%
28
  32.9%
57
  33.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 87 participants 85 participants 172 participants
American Indian or Alaska Native
0
   0.0%
1
   1.2%
1
   0.6%
Asian
1
   1.1%
0
   0.0%
1
   0.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   1.1%
2
   2.4%
3
   1.7%
White
81
  93.1%
80
  94.1%
161
  93.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
4
   4.6%
2
   2.4%
6
   3.5%
Region of Enrollment   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Canada Number Analyzed 1 participants 1 participants 2 participants
1 1 2
Netherlands Number Analyzed 4 participants 1 participants 5 participants
4 1 5
Argentina Number Analyzed 5 participants 8 participants 13 participants
5 8 13
Turkey Number Analyzed 5 participants 7 participants 12 participants
5 7 12
Belgium Number Analyzed 7 participants 6 participants 13 participants
7 6 13
United States Number Analyzed 9 participants 11 participants 20 participants
9 11 20
Brazil Number Analyzed 13 participants 21 participants 34 participants
13 21 34
Italy Number Analyzed 9 participants 8 participants 17 participants
9 8 17
Israel Number Analyzed 6 participants 2 participants 8 participants
6 2 8
France Number Analyzed 3 participants 2 participants 5 participants
3 2 5
Germany Number Analyzed 17 participants 8 participants 25 participants
17 8 25
Spain Number Analyzed 6 participants 6 participants 12 participants
6 6 12
[1]
Measure Analysis Population Description: All randomized participants who received one dose of study drug and had evaluable Region of Enrollment data.
1.Primary Outcome
Title Progression-free Survival (PFS)
Hide Description PFS was defined as the time from date of randomization until the date of disease progression, or death from any cause, whichever was first. Disease progression was assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, and/or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions. Participants without documentation for disease progression or death were censored at the date of last tumor assessment. The PFS was estimated following the Kaplan-Meier method.
Time Frame Randomization Date to Disease Progression or Death From Any Cause Up to 18.3 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants. Participants censored in Cixutumumab arm = 20 and Pemetrexed + Cisplatin arm = 21.
Arm/Group Title Pemetrexed + Cisplatin + Cixutumumab Pemetrexed + Cisplatin
Hide Arm/Group Description:

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Overall Number of Participants Analyzed 87 85
Median (95% Confidence Interval)
Unit of Measure: months
5.45
(3.88 to 6.05)
5.22
(4.24 to 6.74)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pemetrexed + Cisplatin + Cixutumumab, Pemetrexed + Cisplatin
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.848
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.73 to 1.47
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants Achieving an Objective Response Rate (ORR)
Hide Description The ORR is the percentage of all participants with Partial Response (PR) or Complete Response (CR) according to RECIST v1.1. Disease progression was defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, and/or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions. ORR is confirmed best overall tumor response of CR and PR. CR was defined as the disappearance of all target and non-target lesions; 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 Randomization to Disease Progression Up to 18.3 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Pemetrexed + Cisplatin + Cixutumumab Pemetrexed + Cisplatin
Hide Arm/Group Description:

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Overall Number of Participants Analyzed 87 85
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
37.9
(27.7 to 49.0)
30.6
(21.0 to 41.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pemetrexed + Cisplatin + Cixutumumab, Pemetrexed + Cisplatin
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.338
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival is defined as the time from the date of randomization to the date of death from any cause. If the participant is alive at the end of the follow-up period or is lost to follow-up, OS will be censored on the last date the participant is known to be alive. OS was estimated using the Kaplan-Meier method.
Time Frame Randomization Date to Death From Any Cause Up to 20 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants. Participants censored cixutumumab arm = 47 and pemetrexed + cisplatin arm = 39.
Arm/Group Title Pemetrexed + Cisplatin + Cixutumumab Pemetrexed + Cisplatin
Hide Arm/Group Description:

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Overall Number of Participants Analyzed 87 85
Median (95% Confidence Interval)
Unit of Measure: Months
10.68 [1] 
(8.74 to NA)
10.38
(7.43 to 14.39)
[1]
The upper limit was not estimable due to the data had insufficient overall survival data events.
4.Secondary Outcome
Title Duration of Response (DOR)
Hide Description Duration of response is measured from the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that the criteria for PD is met, or death, is objectively documented. DOR was estimated using the Kaplan-Meier method. Disease progression was assessed via RECIST version 1.1, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, and/or the appearance of one or more new lesion(s), and/or unequivocal progression of existing non-target lesions
Time Frame Time from Response to Disease Progression or Death from Any Cause Up to 20 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had CR or PR. Participants censored in Cixutumumab arm = 10 and Pemetrexed + Cisplatin arm = 8.
Arm/Group Title Pemetrexed + Cisplatin + Cixutumumab Pemetrexed + Cisplatin
Hide Arm/Group Description:

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Overall Number of Participants Analyzed 33 26
Median (95% Confidence Interval)
Unit of Measure: Months
4.90
(4.17 to 6.28)
3.91
(2.92 to 6.41)
5.Secondary Outcome
Title Time to Progressive Disease (TTPS)
Hide Description TTPS was defined as the time from the date of randomization until the date of disease progression. Disease progression was assessed via RECIST version 1.1, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, and/or the appearance of one or more new lesion(s), and/or unequivocal progression of existing non-target lesions.TTPS was estimated using the Kaplan-Meier method.
Time Frame Randomization Date to Disease Progression Up to 18.3 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants. Participants censored in Cixutumumab arm = 39 and in the Pemetrexed + Cisplatin arm = 36.
Arm/Group Title Pemetrexed + Cisplatin + Cixutumumab Pemetrexed + Cisplatin
Hide Arm/Group Description:

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Overall Number of Participants Analyzed 87 85
Median (95% Confidence Interval)
Unit of Measure: Months
6.05
(5.32 to 7.79)
6.05
(4.93 to 7.89)
6.Secondary Outcome
Title Time to Worsening of Symptoms as Measured by Lung Cancer Symptom Scale (LCSS) Score
Hide Description TTPS was defined as the time from the date of randomization until the date of worsening of symptoms as measured by Lung Cancer Symptom Scale (LCSS) score. Symptomatic progression was defined as an increase (worsening) of the Average Symptomatic Burden Index (ASBI) that is, the mean of the six major lung cancer specific symptom scores of the LCSS patient scale - ranging from 0 to 100 where higher score indicates worst outcome). For each participant, the maximum improvement over baseline score was calculated for each of the 9 LCSS items, ASBI and LCSS total score. Participants without event are censored at the date of the last LCSS assessment. TTPS was estimated using the Kaplan-Meier method.
Time Frame Time to worsening of symptoms as measured by LCSS score Up to 18.3 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants. Participants censored in Cixutumumab arm = 38 and Pemetrexed + Cisplatin arm = 46.
Arm/Group Title Pemetrexed + Cisplatin + Cixutumumab Pemetrexed + Cisplatin
Hide Arm/Group Description:

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Overall Number of Participants Analyzed 87 85
Median (95% Confidence Interval)
Unit of Measure: Months
2.14
(1.54 to 2.99)
4.21
(2.43 to 5.36)
7.Secondary Outcome
Title Change in Tumor Size (CTS)
Hide Description CTS was measured by percentage change of tumor size at the end of Cycle 2 comparing to baseline tumor size.
Time Frame Change from baseline measurement to the end of Cycle 2, average of 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title Pemetrexed + Cisplatin + Cixutumumab Pemetrexed + Cisplatin
Hide Arm/Group Description:

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Overall Number of Participants Analyzed 87 85
Mean (Standard Deviation)
Unit of Measure: Percent Change
-23.88  (18.859) -16.04  (26.143)
8.Secondary Outcome
Title Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Cixutumumab, Cycle 1 (First Infusion) and Cycle 4 (Fourth Infusion)
Hide Description [Not Specified]
Time Frame First Infusion: [Prior to Infusion (of Cycle1): 1, 72, 168, 336 hours(hrs) and 504 hrs (i.e. Prior to Infusion of Cycle 2)] and Fourth Infusion; [Prior to Infusion (of Cycle 4),1,24,72,120,168,240,336 hrs and 504 hrs (i.e. Prior to Infusion of Cycle 5)]
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who were randomized to the cixutumumab arm and had evaluable PK data.
Arm/Group Title Pemetrexed + Cisplatin + Cixutumumab
Hide Arm/Group Description:

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Overall Number of Participants Analyzed 71
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: microgram/milliliter (ug/mL)
First Infusion Number Analyzed 71 participants
481
(33%)
Fourth Infusion Number Analyzed 31 participants
556
(17%)
9.Secondary Outcome
Title PK: Area Under the Concentration Time Curve (AUC[0-inf]) of Cixutumumab, Cycle 1 (i.e. First Infusion)
Hide Description [Not Specified]
Time Frame Prior to Infusion (of Cycle 1), 1, 72, 168, 336 hrs and 504 hrs (i.e. Prior to Infusion of Cycle 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who were randomized to the cixutumumab arm and had evaluable PK data.
Arm/Group Title Pemetrexed + Cisplatin + Cixutumumab
Hide Arm/Group Description:

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Overall Number of Participants Analyzed 57
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: microgram*hour/milliliter (ug*hr/mL)
73200
(35%)
10.Secondary Outcome
Title PK: Area Under the Concentration Time Curve During 1 Dosing Interval (i.e. 504 hr, AUC(0-tau) of Cixutumumab, Cycle 4 (i.e. Fourth Infusion)
Hide Description [Not Specified]
Time Frame Prior to Infusion (of Cycle 4), 1, 24, 72, 120, 168, 240, 336 hrs and 504 hrs (i.e. Prior to Infusion of Cycle 5)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who were randomized to the cixutumumab arm and had evaluable PK data.
Arm/Group Title Pemetrexed + Cisplatin + Cixutumumab
Hide Arm/Group Description:

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Overall Number of Participants Analyzed 27
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: (ug*hr/mL)
79700
(30%)
11.Secondary Outcome
Title Pharmacodynamics (PD) Markers: Free Insulin-like Growth Factor-I (IGF-I, Total IGF-I, and IGF Binding Proteins (IGFBP-3)
Hide Description Blood samples for the determination of PD marker concentrations were collected at the specified time points for all participants. Analysis of the following markers include free IGF-I, total IGF-I, and IGFBP-3.
Time Frame Preinfusion, Cycle 2, Cycle 4, Cycle 8, Postinfusion, 30-Day Follow-Up
Hide Outcome Measure Data
Hide Analysis Population Description
Zero participants were analyzed for PD Biomarker IGF-I, total IGF-I, and IGFBP-3 due to blood samples were not collected in order to assess biomarker data.
Arm/Group Title Pemetrexed + Cisplatin + Cixutumumab Pemetrexed + Cisplatin
Hide Arm/Group Description:

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
12.Secondary Outcome
Title Immunogenicity of Cixutumumab
Hide Description [Not Specified]
Time Frame Preinfusion, Cycle1(C1): 1, 72, 168, 240, 336 hours(hrs); C2 and C3: 1, 168, 336 hrs; C4: 1, 24,72,120,168, 240, 336, 504 hrs, Postinfusion; 30 Day Follow Up
Hide Outcome Measure Data
Hide Analysis Population Description
Zero participants were analyzed due to no immunogenicity analysis was done and the assay was never developed.
Arm/Group Title Pemetrexed + Cisplatin + Cixutumumab
Hide Arm/Group Description:

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description 6 participants did not receive study drug after randomization. 2 of the participants were in the cixutumumab arm and 4 of the participants were in the control arm.
 
Arm/Group Title Pemetrexed + Cisplatin + Cixutumumab Pemetrexed + Cisplatin
Hide Arm/Group Description

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 plus cixutumumab 20 mg/kg given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Induction Treatment: Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2 given IV on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for participants with significant tumor size reduction, after sponsor approval.

Maintenance Therapy: Pemetrexed 500 mg/m^2 given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

All-Cause Mortality
Pemetrexed + Cisplatin + Cixutumumab Pemetrexed + Cisplatin
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Pemetrexed + Cisplatin + Cixutumumab Pemetrexed + Cisplatin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   49/85 (57.65%)      31/81 (38.27%)    
Blood and lymphatic system disorders     
Anaemia  1  6/85 (7.06%)  18 1/81 (1.23%)  1
Febrile neutropenia  1  3/85 (3.53%)  3 5/81 (6.17%)  5
Leukopenia  1  0/85 (0.00%)  0 1/81 (1.23%)  1
Neutropenia  1  4/85 (4.71%)  4 2/81 (2.47%)  3
Pancytopenia  1  2/85 (2.35%)  7 0/81 (0.00%)  0
Thrombocytopenia  1  1/85 (1.18%)  3 1/81 (1.23%)  4
Cardiac disorders     
Atrial fibrillation  1  0/85 (0.00%)  0 1/81 (1.23%)  1
Myocardial infarction  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Pericarditis  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Ear and labyrinth disorders     
Vertigo  1  2/85 (2.35%)  3 0/81 (0.00%)  0
Vestibular disorder  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Eye disorders     
Blindness  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain  1  1/85 (1.18%)  1 1/81 (1.23%)  1
Colitis  1  0/85 (0.00%)  0 1/81 (1.23%)  1
Constipation  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Diarrhoea  1  3/85 (3.53%)  3 0/81 (0.00%)  0
Haemorrhoidal haemorrhage  1  0/85 (0.00%)  0 1/81 (1.23%)  1
Inguinal hernia  1  0/85 (0.00%)  0 1/81 (1.23%)  1
Lower gastrointestinal haemorrhage  1  1/85 (1.18%)  2 0/81 (0.00%)  0
Nausea  1  5/85 (5.88%)  5 1/81 (1.23%)  1
Oesophagitis  1  0/85 (0.00%)  0 1/81 (1.23%)  1
Stomatitis  1  2/85 (2.35%)  2 1/81 (1.23%)  1
Upper gastrointestinal haemorrhage  1  2/85 (2.35%)  2 0/81 (0.00%)  0
Vomiting  1  7/85 (8.24%)  9 1/81 (1.23%)  1
General disorders     
Fatigue  1  7/85 (8.24%)  9 1/81 (1.23%)  1
General physical health deterioration  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Malaise  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Mucosal inflammation  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Non-cardiac chest pain  1  2/85 (2.35%)  2 0/81 (0.00%)  0
Pyrexia  1  2/85 (2.35%)  2 2/81 (2.47%)  2
Sudden death  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Hepatobiliary disorders     
Cholecystitis  1  1/85 (1.18%)  2 0/81 (0.00%)  0
Immune system disorders     
Hypersensitivity  1  0/85 (0.00%)  0 1/81 (1.23%)  1
Infections and infestations     
Dengue fever  1  0/85 (0.00%)  0 1/81 (1.23%)  1
Device related infection  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Empyema  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Lobar pneumonia  1  1/85 (1.18%)  1 1/81 (1.23%)  1
Lung abscess  1  0/85 (0.00%)  0 1/81 (1.23%)  1
Lung infection  1  0/85 (0.00%)  0 3/81 (3.70%)  4
Mucosal infection  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Pneumonia  1  3/85 (3.53%)  3 1/81 (1.23%)  1
Pneumonia klebsiella  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Pneumonia pneumococcal  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Postoperative abscess  1  0/85 (0.00%)  0 1/81 (1.23%)  1
Sepsis  1  2/85 (2.35%)  2 1/81 (1.23%)  1
Septic shock  1  1/85 (1.18%)  2 4/81 (4.94%)  7
Streptococcal bacteraemia  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Investigations     
Blood bilirubin increased  1  2/85 (2.35%)  3 0/81 (0.00%)  0
Blood creatinine increased  1  1/85 (1.18%)  1 1/81 (1.23%)  1
Neutrophil count decreased  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Platelet count decreased  1  3/85 (3.53%)  7 0/81 (0.00%)  0
White blood cell count decreased  1  2/85 (2.35%)  7 0/81 (0.00%)  0
Metabolism and nutrition disorders     
Decreased appetite  1  4/85 (4.71%)  4 0/81 (0.00%)  0
Dehydration  1  4/85 (4.71%)  5 0/81 (0.00%)  0
Hyperkalaemia  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Hyperuricaemia  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Hypoalbuminaemia  1  1/85 (1.18%)  2 0/81 (0.00%)  0
Hypocalcaemia  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Hyponatraemia  1  1/85 (1.18%)  1 1/81 (1.23%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Bone pain  1  0/85 (0.00%)  0 1/81 (1.23%)  1
Compartment syndrome  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Muscular weakness  1  0/85 (0.00%)  0 1/81 (1.23%)  1
Rhabdomyolysis  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Metastases to bone  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Tumour pain  1  0/85 (0.00%)  0 1/81 (1.23%)  1
Nervous system disorders     
Cerebral ischaemia  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Ischaemic stroke  1  0/85 (0.00%)  0 1/81 (1.23%)  3
Nervous system disorder  1  0/85 (0.00%)  0 1/81 (1.23%)  1
Peripheral motor neuropathy  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Peripheral sensory neuropathy  1  1/85 (1.18%)  2 0/81 (0.00%)  0
Seizure  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Spinal cord compression  1  0/85 (0.00%)  0 1/81 (1.23%)  1
Syncope  1  1/85 (1.18%)  1 1/81 (1.23%)  1
Transient ischaemic attack  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Psychiatric disorders     
Confusional state  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury  1  5/85 (5.88%)  5 0/81 (0.00%)  0
Renal failure  1  2/85 (2.35%)  2 0/81 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1  0/85 (0.00%)  0 2/81 (2.47%)  2
Dyspnoea  1  2/85 (2.35%)  3 3/81 (3.70%)  3
Epistaxis  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Haemoptysis  1  3/85 (3.53%)  3 2/81 (2.47%)  2
Hypoxia  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Pleural effusion  1  1/85 (1.18%)  2 2/81 (2.47%)  3
Pneumonitis  1  0/85 (0.00%)  0 1/81 (1.23%)  2
Pulmonary embolism  1  1/85 (1.18%)  1 1/81 (1.23%)  1
Pulmonary haemorrhage  1  1/85 (1.18%)  1 1/81 (1.23%)  1
Pulmonary oedema  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Respiratory failure  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Surgical and medical procedures     
Osteosynthesis  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Vascular disorders     
Embolism  1  0/85 (0.00%)  0 1/81 (1.23%)  1
Extremity necrosis  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Haematoma  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Hypertension  1  2/85 (2.35%)  2 0/81 (0.00%)  0
Hypotension  1  2/85 (2.35%)  4 0/81 (0.00%)  0
Peripheral arterial occlusive disease  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Peripheral artery thrombosis  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Venous thrombosis  1  1/85 (1.18%)  1 0/81 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pemetrexed + Cisplatin + Cixutumumab Pemetrexed + Cisplatin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   83/85 (97.65%)      79/81 (97.53%)    
Blood and lymphatic system disorders     
Anaemia  1  33/85 (38.82%)  103 36/81 (44.44%)  98
Leukopenia  1  6/85 (7.06%)  12 5/81 (6.17%)  27
Neutropenia  1  12/85 (14.12%)  29 17/81 (20.99%)  35
Thrombocytopenia  1  8/85 (9.41%)  31 5/81 (6.17%)  9
Ear and labyrinth disorders     
Vertigo  1  9/85 (10.59%)  11 4/81 (4.94%)  4
Eye disorders     
Lacrimation increased  1  8/85 (9.41%)  8 7/81 (8.64%)  10
Gastrointestinal disorders     
Abdominal pain  1  4/85 (4.71%)  6 11/81 (13.58%)  15
Constipation  1  27/85 (31.76%)  39 19/81 (23.46%)  28
Diarrhoea  1  19/85 (22.35%)  29 16/81 (19.75%)  21
Dyspepsia  1  5/85 (5.88%)  5 3/81 (3.70%)  4
Dysphagia  1  5/85 (5.88%)  5 1/81 (1.23%)  1
Nausea  1  45/85 (52.94%)  74 41/81 (50.62%)  101
Stomatitis  1  14/85 (16.47%)  24 6/81 (7.41%)  8
Vomiting  1  29/85 (34.12%)  41 28/81 (34.57%)  55
General disorders     
Asthenia  1  10/85 (11.76%)  12 9/81 (11.11%)  30
Chest pain  1  2/85 (2.35%)  3 5/81 (6.17%)  10
Fatigue  1  36/85 (42.35%)  82 33/81 (40.74%)  63
Influenza like illness  1  1/85 (1.18%)  1 6/81 (7.41%)  7
Mucosal inflammation  1  12/85 (14.12%)  18 3/81 (3.70%)  3
Non-cardiac chest pain  1  3/85 (3.53%)  4 6/81 (7.41%)  6
Oedema peripheral  1  7/85 (8.24%)  7 13/81 (16.05%)  19
Pyrexia  1  5/85 (5.88%)  5 10/81 (12.35%)  14
Infections and infestations     
Conjunctivitis  1  3/85 (3.53%)  5 5/81 (6.17%)  6
Upper respiratory tract infection  1  2/85 (2.35%)  2 6/81 (7.41%)  7
Investigations     
Alanine aminotransferase increased  1  8/85 (9.41%)  11 4/81 (4.94%)  6
Aspartate aminotransferase increased  1  4/85 (4.71%)  4 5/81 (6.17%)  7
Blood creatinine increased  1  12/85 (14.12%)  18 16/81 (19.75%)  20
Neutrophil count decreased  1  9/85 (10.59%)  24 6/81 (7.41%)  10
Platelet count decreased  1  6/85 (7.06%)  6 9/81 (11.11%)  14
Weight decreased  1  17/85 (20.00%)  28 11/81 (13.58%)  13
White blood cell count decreased  1  5/85 (5.88%)  10 4/81 (4.94%)  6
Metabolism and nutrition disorders     
Decreased appetite  1  24/85 (28.24%)  36 27/81 (33.33%)  32
Dehydration  1  10/85 (11.76%)  13 6/81 (7.41%)  8
Hyperglycaemia  1  43/85 (50.59%)  156 16/81 (19.75%)  45
Hyperkalaemia  1  5/85 (5.88%)  8 2/81 (2.47%)  3
Hypocalcaemia  1  5/85 (5.88%)  7 1/81 (1.23%)  1
Hypokalaemia  1  6/85 (7.06%)  7 4/81 (4.94%)  4
Hypomagnesaemia  1  9/85 (10.59%)  13 6/81 (7.41%)  6
Hyponatraemia  1  5/85 (5.88%)  5 4/81 (4.94%)  5
Musculoskeletal and connective tissue disorders     
Back pain  1  9/85 (10.59%)  10 10/81 (12.35%)  13
Bone pain  1  2/85 (2.35%)  3 5/81 (6.17%)  5
Pain in extremity  1  5/85 (5.88%)  6 2/81 (2.47%)  2
Nervous system disorders     
Dizziness  1  11/85 (12.94%)  13 5/81 (6.17%)  7
Dysgeusia  1  7/85 (8.24%)  9 8/81 (9.88%)  10
Paraesthesia  1  2/85 (2.35%)  3 5/81 (6.17%)  5
Psychiatric disorders     
Anxiety  1  3/85 (3.53%)  3 5/81 (6.17%)  6
Depression  1  5/85 (5.88%)  5 4/81 (4.94%)  4
Insomnia  1  5/85 (5.88%)  5 7/81 (8.64%)  10
Respiratory, thoracic and mediastinal disorders     
Cough  1  13/85 (15.29%)  21 16/81 (19.75%)  20
Dyspnoea  1  14/85 (16.47%)  21 16/81 (19.75%)  26
Epistaxis  1  7/85 (8.24%)  11 0/81 (0.00%)  0
Productive cough  1  1/85 (1.18%)  1 5/81 (6.17%)  14
Skin and subcutaneous tissue disorders     
Alopecia  1  7/85 (8.24%)  8 3/81 (3.70%)  3
Rash  1  7/85 (8.24%)  7 4/81 (4.94%)  5
Vascular disorders     
Hypotension  1  8/85 (9.41%)  8 1/81 (1.23%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
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: NCT01232452    
Other Study ID Numbers: 13973
I5A-MC-JAEM ( Other Identifier: Eli Lilly and Company )
First Submitted: October 28, 2010
First Posted: November 2, 2010
Results First Submitted: March 17, 2018
Results First Posted: June 12, 2018
Last Update Posted: September 20, 2019