INSPIRE: First-line Treatment of Patients With Stage IV Nonsquamous Non-Small Cell Lung Cancer With Necitumumab (IMC-11F8) and Pemetrexed-Cisplatin
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT00982111
Collaborator
Quintiles, Inc. (Industry), Parexel (Industry), PPD (Industry), Medidata Solutions (Industry), Laboratory Corporation of America (Industry), University of Colorado, Denver (Other), Thermo Fisher Scientific, Inc (Industry), Pacific Biomarkers (Other), Intertek (Industry), Sysmex Inostics GmbH (Industry)
633
101
2
133.7
6.3
0
Study Details
Study Description
Brief Summary
The research study is testing the investigational drug necitumumab in the treatment of advanced non-small cell lung cancer. The aim of this study is to determine if necitumumab, given together with a standard chemotherapy combination consisting of cisplatin and pemetrexed will be more effective in improving participant disease than the standard chemotherapy combination alone.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Multinational, randomized, multicenter, open-label Phase 3 study of 633 participants with advanced, nonsquamous (Stage IV) NSCLC. Participants will be randomized on a 1:1 basis to receive first-line necitumumab plus chemotherapy consisting of pemetrexed and cisplatin in study Arm A, or first-line pemetrexed-cisplatin chemotherapy alone in Arm B.
Baseline radiographic assessment of disease will be performed within 21 days prior to randomization (first treatment will be administered within 7 days following randomization).
Participants will undergo radiographic assessment (computed tomography or magnetic resonance imaging) of disease status every 6 weeks (± 3 days), until there is radiographic documentation of progressive disease (PD). Chemotherapy will continue for a maximum of six cycles in each arm (Or until there is radiographic documentation of PD, toxicity requiring cessation, protocol noncompliance or withdrawal of consent); participants in Arm A only will continue to receive necitumumab until there is radiographic documentation of PD, toxicity requiring cessation, protocol noncompliance, or withdrawal of consent.
After the end-of-study-visit (following PD), follow-up information regarding further anticancer treatment and survival will be collected every 2 months (± 7 days). For participants who discontinue study for reasons other than PD (eg, symptomatic deterioration), information on disease progression will also be collected until PD is documented. Follow-up will continue as long as the participant is alive, or until the end of the trial.
Study Design
Study Type:
Interventional
Actual Enrollment
:
633 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized, Multicenter, Open-Label Phase 3 Study of Pemetrexed-Cisplatin Chemotherapy Plus Necitumumab (IMC-11F8) Versus Pemetrexed-Cisplatin Chemotherapy Alone in the First-Line Treatment of Patients With Stage IV Nonsquamous Non-Small Cell Lung Cancer (NSCLC)
Actual Study Start Date
:
Nov 2, 2009
Actual Primary Completion Date
:
Nov 14, 2012
Actual Study Completion Date
:
Dec 23, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Necitumumab + Pemetrexed + Cisplatin Necitumumab + Pemetrexed + Cisplatin |
Drug: Pemetrexed
500 milligram per square meter (mg/m2) administered Intravenously (I.V.) on Day 1 of every 3-week cycle, for a maximum of six cycles
Other Names:
Drug: Cisplatin
75 mg/m2 administered I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles
Biological: Necitumumab
800 mg (absolute dose) on Days 1 and 8 of every 3-week cycle, administered as an I.V.
Other Names:
|
| Active Comparator: Pemetrexed + Cisplatin Pemetrexed + Cisplatin |
Drug: Pemetrexed
500 milligram per square meter (mg/m2) administered Intravenously (I.V.) on Day 1 of every 3-week cycle, for a maximum of six cycles
Other Names:
Drug: Cisplatin
75 mg/m2 administered I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles
|
Outcome Measures
Primary Outcome Measures
- Overall Survival Time (OS) [Randomization to Death from Any Cause (Up to 31.6 Months)]
OS is defined as the time from randomization to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive. OS was estimated using the Kaplan-Meier method.
Secondary Outcome Measures
- Progression-Free Survival (PFS) [Randomization to Measured Progressive Disease or Death from Any Cause (Up to 30.4 Months)]
PFS is defined as the time from randomization until the first radiographic documentation of measured progressive disease as defined by RECIST (Version 1.0), or death from any cause. Participants who die without a reported prior progression will be considered to have progressed on the day of their death. Participants who did not progress or were lost to follow-up were censored at the day of their last radiographic tumor assessment. If no baseline or postbaseline radiologic assessment was available, the participant was censored at the date of randomization. If death or PD occurs after two or more consecutive missing radiographic visits, censoring occurred at the date of the last radiographic visit prior to the missed visits.
- Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Tumor Response Rate [ORR]) [Baseline to Measured Progressive Disease (Up to 30.4 Months)]
ORR is confirmed best overall tumor response of CR or PR. According to RECIST v1.0, 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. 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.
- Time to Treatment Failure (TTF) [Randomization to Measured Progressive Disease, Death from Any Cause, Discontinuation of Treatment or Initiation of New Anticancer Therapy (Up to 30.4 Months)]
TTF was defined as the time from study enrollment/randomization to the first observation of measured progressive disease, death from any cause, or early discontinuation of treatment or initiation of new anti-cancer therapies. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Progressive Disease (PD) was defined as having at least a 20% increase in sum of longest diameter of target lesions. Time to treatment failure was censored at the date of the last follow-up visit for participants who did not discontinue early, who were still alive, and who have not progressed.
- Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab [Predose Day 1 of Cycle 2,3,4,5 and 6 Prior to Necitumumab Infusion, Up to 23 Weeks]
- Number of Participants With Serum Anti-Necitumumab Antibody Assessment (Immunogenicity) [Baseline to Study Completion (Up to 31.6 Months)]
A participant was considered to have an anti-Necitumumab antibody response if anti-drug antibodies (ADA) were confirmed positive. Treatment emergent antibodies were defined as any anti-Necitumumab antibody titer equal to or greater than 4-fold the participant's baseline titer.
- Mean Change From Baseline in Patient Reported Outcomes (PRO) Using the European Quality of Life-5 Dimensions (EQ-5D) [Baseline, Cycle 6 (Cycle = 3 weeks)]
The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a three level scale 1-3 (no problem, some problems, and major problems). These combinations of attributes were converted into a weighted health-state Index Score according to the United Kingdom (UK) population-based algorithm. The possible values for the Index Score ranged from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension).
- Mean Change From Baseline in PRO as Measured Using the Lung Cancer Symptom Scale (LCSS) [Baseline, Cycle 6 (Cycle =3 Weeks)]
The LCSS consisted of 9 items: 6 items focused on lung cancer symptoms [loss of appetite, fatigue, cough, dyspnea (shortness of breath), hemoptysis (blood in sputum), and pain] and 3 items were global items (symptom distress, interference with activity level, and global quality of life). Participant responses to each item were measured using visual analogue scales (VAS) with 100-mm lines. A higher score for any item represented a higher level of symptoms/problems. Scores for each of the reported categories ranged from 0 (for best outcome) to 100 (for worst outcome). The Average Symptom Burden Index (ASBI) was the mean of the 6 symptom items of the LCSS, and the Total LCSS was the mean of all 9 LCSS items. ASBI and Total LCSS were not computed for a participant if he/she had 1 or more missing values for the 6 and 9 items, respectively.
- Epidermal Growth Factor Hormone (EGFR) Protein Expression Measured by Immunohistochemistry (IHC) [Baseline]
EGFR IHC H-score = weighted sum of % 1+ cells, twice % 2+ cells, and three times % 3+ cells. IHC H-score criteria assesses participants with a low EGFR expression defined by a H-score cutoff value of < 200 and participants with a high EGFR expression defined by a H-score of cutoff value of >=200.
- Percentage of Participants With EGFR Measured by IHC [Baseline]
EGFR IHC H-score = weighted sum of % 1+ cells, twice % 2+ cells, and three times % 3+ cells. IHC H-score criteria assesses participants with a low EGFR expression defined by a H-score cutoff value of < 200 and participants with a high EGFR expression defined by a H-score of cutoff value of >=200.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Has histologically or cytologically confirmed nonsquamous (adenocarcinoma/large cell or other) non small cell lung cancer
-
Has Stage IV disease at the time of study entry
-
Measurable or nonmeasurable disease (as defined by the Response Evaluation Criteria in Solid Tumors RECIST 1.0) at the time of study entry (participants with only truly nonmeasurable disease are not eligible)
-
Has resolution to Grade ≤ 1 of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy (with the exception of alopecia)
-
Has an Eastern Cooperative Oncology Group performance status score of 0-2
-
Has adequate hepatic function
-
Has adequate renal function
-
Has adequate hematologic function
-
If female, is surgically sterile, postmenopausal, or compliant with a highly effective contraceptive method during and for 6 months after the treatment period (oral hormonal contraception alone is not considered highly effective and must be used in combination with a barrier method). If male, the participants surgically sterile or compliant with a highly effective contraceptive regimen during and for 6 months after the treatment period
-
Female participants of childbearing potential must have a negative serum
Exclusion Criteria:
-
Has squamous non small cell lung cancer
-
Has received prior anticancer therapy with monoclonal antibodies, signal transduction inhibitors, or any therapies targeting the Epidermal Growth Factor Hormone (EGFR), vascular endothelial growth factor (VEGF), or VEGF receptor
-
Received previous chemotherapy for advanced NSCLC (participants who have received adjuvant chemotherapy are eligible if the last administration of the prior adjuvant regimen occurred at least 1 year prior to randomization)
-
Undergone major surgery or received any investigational therapy in the 4 weeks prior to randomization
-
Undergone chest irradiation within 12 weeks prior to randomization (except palliative irradiation of bone lesions, which is allowed)
-
Has brain metastases that are symptomatic or require ongoing treatment with steroids or anticonvulsants. Participants who have undergone previous radiotherapy for brain metastases, who are now nonsymptomatic and no longer require treatment with steroids or anticonvulsants, are eligible
-
Has superior vena cava syndrome contraindicating hydration
-
Has current clinically-relevant coronary artery disease or uncontrolled congestive heart failure
-
Has experienced myocardial infarction within 6 months prior to randomization
-
Has an ongoing or active infection (requiring antibiotics), including active tuberculosis or known infection with the human immunodeficiency virus
-
Has a history of significant neurological or psychiatric disorders, including dementia, seizures, or bipolar disorder, potentially precluding protocol compliance
-
Has Grade ≥ 2 peripheral neuropathy
-
Has significant third space fluid retention, requiring repeated drainage
-
Has any other serious uncontrolled medical disorders or psychological conditions that would, in the opinion of the investigator, limit the participant's ability to complete the study or sign an informed consent document The participant has a known allergy / history of hypersensitivity reaction to any of the treatment components, including any ingredient used in the formulation of IMC-11F8, or any other contraindication to one of the administered treatments
-
Is pregnant or breastfeeding
-
Has a known history of drug abuse
-
Has a concurrent active malignancy other than adequately-treated basal cell carcinoma of the skin or preinvasive carcinoma of the cervix. A participant with previous history of malignancy other than NSCLC is eligible, provided that he/she has been free of disease for ≥ 3 years
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | ImClone Investigational Site | Nyack | New York | United States | 10960 |
| 2 | ImClone Investigational Site | Kogarah | New South Wales | Australia | 2217 |
| 3 | ImClone Investigational Site | Hobart | Tasmania | Australia | 7000 |
| 4 | ImClone Investigational Site | East Bentleigh | Victoria | Australia | 3165 |
| 5 | ImClone Investigational Site | Rankweil | Austria | 6830 | |
| 6 | ImClone Investigational Site | Wien | Austria | 1090 | |
| 7 | ImClone Investigational Site | Wien | Austria | 1130 | |
| 8 | ImClone Investigational Site | Duffel | Belgium | 2570 | |
| 9 | ImClone Investigational Site | Liège | Belgium | 4000 | |
| 10 | ImClone Investigational Site | Namur | Belgium | 5000 | |
| 11 | ImClone Investigational Site | Barretos - SP | Brazil | 14784-400 | |
| 12 | ImClone Investigational Site | Brasilia, Distrito Federal | Brazil | 70310-050 | |
| 13 | ImClone Investigational Site | Goiania - GO | Brazil | 74884-606 | |
| 14 | ImClone Investigational Site | Ijui | Brazil | 98700-000 | |
| 15 | ImClone Investigational Site | Itajai | Brazil | 88301-220 | |
| 16 | ImClone Investigational Site | Lajeado | Brazil | 95900-000 | |
| 17 | ImClone Investigational Site | Porto Alegre/RS | Brazil | 90610-000 | |
| 18 | ImClone Investigational Site | Ribeirão Preto - SP | Brazil | 14015-130 | |
| 19 | ImClone Investigational Site | Salvador | Brazil | 40050-410 | |
| 20 | ImClone Investigational Site | Santo Andre - SP | Brazil | 09090-780 | |
| 21 | ImClone Investigational Site | São Paulo - SP | Brazil | 01246-000 | |
| 22 | ImClone Investigational Site | Montreal | Quebec | Canada | H3T 1E2 |
| 23 | ImClone Investigational Site | Pula | Croatia | 52100 | |
| 24 | ImClone Investigational Site | Caen | France | 14076 | |
| 25 | ImClone Investigational Site | Paris | France | 75571 | |
| 26 | ImClone Investigational Site | Berlin | Germany | 12200 | |
| 27 | ImClone Investigational Site | Essen | Germany | 45136 | |
| 28 | ImClone Investigational Site | Frankfurt | Germany | 60487 | |
| 29 | ImClone Investigational Site | Gauting | Germany | 82131 | |
| 30 | ImClone Investigational Site | Großhansdorf | Germany | 22927 | |
| 31 | ImClone Investigational Site | Halle | Germany | 06120 | |
| 32 | ImClone Investigational Site | Hamburg | Germany | 21075 | |
| 33 | ImClone Investigational Site | Heidelberg | Germany | 69126 | |
| 34 | ImClone Investigational Site | Hemer | Germany | 58675 | |
| 35 | ImClone Investigational Site | Hofheim | Germany | 65719 | |
| 36 | ImClone Investigational Site | Karlsruhe | Germany | 76137 | |
| 37 | ImClone Investigational Site | Lostau | Germany | 39291 | |
| 38 | ImClone Investigational Site | Löwenstein | Germany | 74245 | |
| 39 | ImClone Investigational Site | Mainz | Germany | 55131 | |
| 40 | ImClone Investigational Site | München | Germany | 81675 | |
| 41 | ImClone Investigational Site | Münster | Germany | 48149 | |
| 42 | ImClone Investigational Site | Regensburg | Germany | 93053 | |
| 43 | ImClone Investigational Site | Ulm | Germany | 89081 | |
| 44 | ImClone Investigational Site | Athens | Greece | 11527 | |
| 45 | ImClone Investigational Site | Heraklion, Crete | Greece | 71110 | |
| 46 | ImClone Investigational Site | Patras | Greece | 26500 | |
| 47 | ImClone Investigational Site | Budapest | Hungary | 1125 | |
| 48 | ImClone Investigational Site | Budapest | Hungary | 1145 | |
| 49 | ImClone Investigational Site | Deszk | Hungary | 6772 | |
| 50 | ImClone Investigational Site | Mosonmagyaróvár | Hungary | 9200 | |
| 51 | ImClone Investigational Site | Szombathely | Hungary | 9700 | |
| 52 | ImClone Investigational Site | Székesfehérvár | Hungary | 8000 | |
| 53 | ImClone Investigational Site | Törökbálint | Hungary | 2045 | |
| 54 | ImClone Investigational Site | Lido di Camaiore | Lucca | Italy | 55041 |
| 55 | ImClone Investigational Site | Aviano | Pordenone | Italy | 33081 |
| 56 | ImClone Investigational Site | Frosinone | Italy | 03100 | |
| 57 | ImClone Investigational Site | Genova | Italy | 16132 | |
| 58 | ImClone Investigational Site | Milano | Italy | 20133 | |
| 59 | ImClone Investigational Site | Parma | Italy | 43100 | |
| 60 | ImClone Investigational Site | Perugia | Italy | 06126 | |
| 61 | ImClone Investigational Site | Olsztyn | Poland | 10-357 | |
| 62 | ImClone Investigational Site | Otwock | Poland | 05-400 | |
| 63 | ImClone Investigational Site | Poznan | Poland | 60-569 | |
| 64 | ImClone Investigational Site | Radom | Poland | 26-617 | |
| 65 | ImClone Investigational Site | Szczecin | Poland | 70-891 | |
| 66 | ImClone Investigational Site | Wroclaw | Poland | 53-439 | |
| 67 | ImClone Investigational Site | Coimbra | Portugal | 3041-801 | |
| 68 | ImClone Investigational Site | Lisboa | Portugal | 1649-035 | |
| 69 | ImClone Investigational Site | Brasov | Romania | 500366 | |
| 70 | ImClone Investigational Site | Bucharest | Romania | 022328 | |
| 71 | ImClone Investigational Site | Bucharest | Romania | 030171 | |
| 72 | ImClone Investigational Site | Cluj-Napoca | Romania | 400015 | |
| 73 | ImClone Investigational Site | Craiova, Dolj | Romania | 200385 | |
| 74 | ImClone Investigational Site | Iasi | Romania | 700106 | |
| 75 | ImClone Investigational Site | Sibiu | Romania | 550245 | |
| 76 | ImClone Investigational Site | Ivanovo | Russian Federation | 153013 | |
| 77 | ImClone Investigational Site | Kirov | Russian Federation | 610021 | |
| 78 | ImClone Investigational Site | Omsk | Russian Federation | 644013 | |
| 79 | ImClone Investigational Site | St. Petersburg | Russian Federation | 194044 | |
| 80 | ImClone Investigational Site | St. Petersburg | Russian Federation | 197022 | |
| 81 | ImClone Investigational Site | St. Petersburg | Russian Federation | 198255 | |
| 82 | ImClone Investigational Site | Ufa | Russian Federation | 450054 | |
| 83 | ImClone Investigational Site | Yaroslavi | Russian Federation | 150054 | |
| 84 | ImClone Investigational Site | Bratislava | Slovakia | 826 06 | |
| 85 | ImClone Investigational Site | Nitra | Slovakia | 949 88 | |
| 86 | ImClone Investigational Site | Bloemfontein | Free State | South Africa | 9301 |
| 87 | ImClone Investigational Site | Pretoria | Gauteng | South Africa | 0001 |
| 88 | Imclone Investigational Site | Sevilla | Andalucia | Spain | 41013 |
| 89 | ImClone Investigational Site | Barcelona | Cataluña | Spain | 08035 |
| 90 | ImClone Investigational Site | Barcelona | Cataluña | Spain | 08041 |
| 91 | ImClone Investigational Site | Terrassa | Cataluña | Spain | 08221 |
| 92 | ImClone Investigational Site | Madrid | Communidad De Madrid | Spain | 28041 |
| 93 | ImClone Investigational Site | Madrid | Communidad De Madrid | Spain | 28050 |
| 94 | ImClone Investigational Site | Majadahonda | Communidad De Madrid | Spain | 28222 |
| 95 | ImClone Investigational Site | L'Hospitalet de Llobregat | Spain | 08908 | |
| 96 | ImClone Investigational Site | Aberdeen | United Kingdom | AB25 2ZN | |
| 97 | ImClone Investigational Site | Bournemouth | United Kingdom | BH7 7DW | |
| 98 | ImClone Investigational Site | Edinburgh | United Kingdom | EH4 2XU | |
| 99 | ImClone Investigational Site | Guildford | United Kingdom | GU2 7XX | |
| 100 | ImClone Investigational Site | Leeds | United Kingdom | LS16 6QB | |
| 101 | ImClone Investigational Site | Preston | United Kingdom | PR2 9HT |
Sponsors and Collaborators
- Eli Lilly and Company
- Quintiles, Inc.
- Parexel
- PPD
- Medidata Solutions
- Laboratory Corporation of America
- University of Colorado, Denver
- Thermo Fisher Scientific, Inc
- Pacific Biomarkers
- Intertek
- Sysmex Inostics GmbH
Investigators
- Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00982111
Other Study ID Numbers:
- 13908
- 2009-012574-12
- CP11-0805
- I4X-IE-JFCB
First Posted:
Sep 22, 2009
Last Update Posted:
Jan 11, 2022
Last Verified:
Dec 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Eli Lilly and Company
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Completers included participants who died from any cause and participants who were alive and on study at conclusion however were off treatment. |
| Arm/Group Title | Necitumumab + Pemetrexed + Cisplatin | Pemetrexed + Cisplatin |
|---|---|---|
| Arm/Group Description | Necitumumab + Pemetrexed + Cisplatin Necitumumab: 800 milligrams (mg) (absolute dose) on Days 1 and 8 of every 3-week cycle. Pemetrexed: 500 mg/square meter (mg/m2) intravenous (I.V.) on Day 1 of every 3-week cycle, for a maximum of six cycles. Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles. | Pemetrexed + Cisplatin Pemetrexed: 500 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles. Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles. |
| Period Title: Overall Study | ||
| STARTED | 315 | 318 |
| Received at Least 1 Dose of Study Drug | 304 | 312 |
| Death Due to Any Cause | 236 | 246 |
| COMPLETED | 236 | 246 |
| NOT COMPLETED | 79 | 72 |
Baseline Characteristics
| Arm/Group Title | Necitumumab + Pemetrexed + Cisplatin | Pemetrexed + Cisplatin | Total |
|---|---|---|---|
| Arm/Group Description | Necitumumab: 800 mg (absolute dose) on Days 1 and 8 of every 3-week cycle, administered as an I.V. infusion Pemetrexed: 500 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles | Pemetrexed + Cisplatin Pemetrexed: 500 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles | Total of all reporting groups |
| Overall Participants | 315 | 318 | 633 |
| Age, Customized (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
61.0
|
60.0
|
61.00
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
101
32.1%
|
108
34%
|
209
33%
|
| Male |
214
67.9%
|
210
66%
|
424
67%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
47
14.9%
|
46
14.5%
|
93
14.7%
|
| Not Hispanic or Latino |
268
85.1%
|
272
85.5%
|
540
85.3%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
2
0.6%
|
0
0%
|
2
0.3%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
8
2.5%
|
9
2.8%
|
17
2.7%
|
| White |
292
92.7%
|
298
93.7%
|
590
93.2%
|
| More than one race |
13
4.1%
|
11
3.5%
|
24
3.8%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| Russian Federation |
16
5.1%
|
13
4.1%
|
29
4.6%
|
| Romania |
21
6.7%
|
31
9.7%
|
52
8.2%
|
| Hungary |
23
7.3%
|
22
6.9%
|
45
7.1%
|
| United States |
0
0%
|
1
0.3%
|
1
0.2%
|
| United Kingdom |
11
3.5%
|
11
3.5%
|
22
3.5%
|
| Portugal |
6
1.9%
|
1
0.3%
|
7
1.1%
|
| Spain |
40
12.7%
|
27
8.5%
|
67
10.6%
|
| Greece |
5
1.6%
|
10
3.1%
|
15
2.4%
|
| Canada |
2
0.6%
|
1
0.3%
|
3
0.5%
|
| Austria |
8
2.5%
|
11
3.5%
|
19
3%
|
| Belgium |
8
2.5%
|
9
2.8%
|
17
2.7%
|
| Brazil |
37
11.7%
|
35
11%
|
72
11.4%
|
| Poland |
28
8.9%
|
24
7.5%
|
52
8.2%
|
| Italy |
17
5.4%
|
19
6%
|
36
5.7%
|
| South Africa |
2
0.6%
|
5
1.6%
|
7
1.1%
|
| Slovakia |
3
1%
|
1
0.3%
|
4
0.6%
|
| Australia |
6
1.9%
|
8
2.5%
|
14
2.2%
|
| France |
7
2.2%
|
3
0.9%
|
10
1.6%
|
| Germany |
75
23.8%
|
84
26.4%
|
159
25.1%
|
| Croatia |
0
0%
|
2
0.6%
|
2
0.3%
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) at Baseline (participants) [Number] | |||
| 0 |
115
36.5%
|
132
41.5%
|
247
39%
|
| 1 |
183
58.1%
|
166
52.2%
|
349
55.1%
|
| 2 |
16
5.1%
|
20
6.3%
|
36
5.7%
|
| Missing |
1
0.3%
|
0
0%
|
1
0.2%
|
| Smoking (participants) [Number] | |||
| Ex-Light Smoker |
26
8.3%
|
27
8.5%
|
53
8.4%
|
| Nonsmoker |
51
16.2%
|
53
16.7%
|
104
16.4%
|
| Smoker |
238
75.6%
|
238
74.8%
|
476
75.2%
|
| Disease Stage at Study Entry (participants) [Number] | |||
| Stage IIIB |
9
2.9%
|
11
3.5%
|
20
3.2%
|
| Stage IV |
305
96.8%
|
307
96.5%
|
612
96.7%
|
| Missing |
1
0.3%
|
0
0%
|
1
0.2%
|
| Disease Histology (participants) [Number] | |||
| Adenocarcinoma/Large Cell Carcinoma |
307
97.5%
|
311
97.8%
|
618
97.6%
|
| Other |
7
2.2%
|
7
2.2%
|
14
2.2%
|
| Missing |
1
0.3%
|
0
0%
|
1
0.2%
|
| Sites of Metastatic Disease (participants) [Number] | |||
| Bone |
103
32.7%
|
109
34.3%
|
212
33.5%
|
| Brain |
27
8.6%
|
25
7.9%
|
52
8.2%
|
| Liver |
58
18.4%
|
64
20.1%
|
122
19.3%
|
| Lung |
259
82.2%
|
268
84.3%
|
527
83.3%
|
| Lymph Nodes |
239
75.9%
|
240
75.5%
|
479
75.7%
|
| Peritoneal |
21
6.7%
|
22
6.9%
|
43
6.8%
|
| Pleural |
111
35.2%
|
111
34.9%
|
222
35.1%
|
| Skin |
7
2.2%
|
5
1.6%
|
12
1.9%
|
| Soft Tissue |
19
6%
|
21
6.6%
|
40
6.3%
|
| Other |
87
27.6%
|
93
29.2%
|
180
28.4%
|
Outcome Measures
| Title | Overall Survival Time (OS) |
|---|---|
| Description | OS is defined as the time from randomization to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive. OS was estimated using the Kaplan-Meier method. |
| Time Frame | Randomization to Death from Any Cause (Up to 31.6 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants. Censored participants: Necitumumab + Pemetrexed + Cisplatin =79, Pemetrexed + Cisplatin=72 |
| Arm/Group Title | Necitumumab + Pemetrexed + Cisplatin | Pemetrexed + Cisplatin |
|---|---|---|
| Arm/Group Description | Necitumumab + Pemetrexed + Cisplatin Necitumumab: 800 mg (absolute dose) on Days 1 and 8 of every 3-week cycle, administered as an I.V. infusion Pemetrexed: 500 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles | Pemetrexed + Cisplatin Pemetrexed: 500 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles |
| Measure Participants | 315 | 318 |
| Median (95% Confidence Interval) [Months] |
11.3
|
11.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Necitumumab + Pemetrexed + Cisplatin, Pemetrexed + Cisplatin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9561 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.01 | |
| Confidence Interval |
(2-Sided) 95% 0.84 to 1.21 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Progression-Free Survival (PFS) |
|---|---|
| Description | PFS is defined as the time from randomization until the first radiographic documentation of measured progressive disease as defined by RECIST (Version 1.0), or death from any cause. Participants who die without a reported prior progression will be considered to have progressed on the day of their death. Participants who did not progress or were lost to follow-up were censored at the day of their last radiographic tumor assessment. If no baseline or postbaseline radiologic assessment was available, the participant was censored at the date of randomization. If death or PD occurs after two or more consecutive missing radiographic visits, censoring occurred at the date of the last radiographic visit prior to the missed visits. |
| Time Frame | Randomization to Measured Progressive Disease or Death from Any Cause (Up to 30.4 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants. Censored participants: Necitumumab + Pemetrexed + Cisplatin=84, Pemetrexed + Cisplatin=79 |
| Arm/Group Title | Necitumumab + Pemetrexed + Cisplatin | Pemetrexed + Cisplatin |
|---|---|---|
| Arm/Group Description | Necitumumab + Pemetrexed + Cisplatin Necitumumab: 800 mg (absolute dose) on Days 1 and 8 of every 3-week cycle, administered as an I.V. infusion Pemetrexed: 500 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles | Pemetrexed + Cisplatin Pemetrexed: 500 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles |
| Measure Participants | 315 | 318 |
| Median (95% Confidence Interval) [Months] |
5.6
|
5.6
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Necitumumab + Pemetrexed + Cisplatin, Pemetrexed + Cisplatin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6647 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.96 | |
| Confidence Interval |
(2-Sided) 95% 0.80 to 1.16 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Tumor Response Rate [ORR]) |
|---|---|
| Description | ORR is confirmed best overall tumor response of CR or PR. According to RECIST v1.0, 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. 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. |
| Time Frame | Baseline to Measured Progressive Disease (Up to 30.4 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants. |
| Arm/Group Title | Necitumumab + Pemetrexed + Cisplatin | Pemetrexed + Cisplatin |
|---|---|---|
| Arm/Group Description | Necitumumab + Pemetrexed + Cisplatin Necitumumab: 800 mg (absolute dose) on Days 1 and 8 of every 3-week cycle, administered as an I.V. infusion Pemetrexed: 500 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles | Pemetrexed + Cisplatin Pemetrexed: 500 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles |
| Measure Participants | 315 | 318 |
| Number (95% Confidence Interval) [percentage of participants] |
31.1
9.9%
|
32.1
10.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Necitumumab + Pemetrexed + Cisplatin, Pemetrexed + Cisplatin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7945 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.96 | |
| Confidence Interval |
(2-Sided) 95% 0.68 to 1.34 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Treatment Failure (TTF) |
|---|---|
| Description | TTF was defined as the time from study enrollment/randomization to the first observation of measured progressive disease, death from any cause, or early discontinuation of treatment or initiation of new anti-cancer therapies. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Progressive Disease (PD) was defined as having at least a 20% increase in sum of longest diameter of target lesions. Time to treatment failure was censored at the date of the last follow-up visit for participants who did not discontinue early, who were still alive, and who have not progressed. |
| Time Frame | Randomization to Measured Progressive Disease, Death from Any Cause, Discontinuation of Treatment or Initiation of New Anticancer Therapy (Up to 30.4 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants. Censored participants: Necitumumab + Pemetrexed + Cisplatin = 10, Pemetrexed + Cisplatin = 13 |
| Arm/Group Title | Necitumumab + Pemetrexed + Cisplatin | Pemetrexed + Cisplatin |
|---|---|---|
| Arm/Group Description | Necitumumab + Pemetrexed + Cisplatin Necitumumab: 800 mg (absolute dose) on Days 1 and 8 of every 3-week cycle, administered as an I.V. infusion Pemetrexed: 500 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles | Pemetrexed + Cisplatin Pemetrexed: 500 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles |
| Measure Participants | 315 | 318 |
| Median (95% Confidence Interval) [Months] |
3.5
|
4.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Necitumumab + Pemetrexed + Cisplatin, Pemetrexed + Cisplatin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0459 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.18 | |
| Confidence Interval |
(2-Sided) 95% 1.00 to 1.39 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab |
|---|---|
| Description | |
| Time Frame | Predose Day 1 of Cycle 2,3,4,5 and 6 Prior to Necitumumab Infusion, Up to 23 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who were randomized to necitumumab and had evaluable PK data. |
| Arm/Group Title | Necitumumab + Pemetrexed + Cisplatin |
|---|---|
| Arm/Group Description | Necitumumab + Pemetrexed + Cisplatin Necitumumab: 800 mg (absolute dose) on Days 1 and 8 of every 3-week cycle, administered as an I.V. infusion Pemetrexed: 500 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles |
| Measure Participants | 315 |
| Predose Cycle 2 Day 1 |
57.5
(84.5)
|
| Predose Cycle 3 Day 1 |
80.8
(89.3)
|
| Predose Cycle 4 Day 1 |
110
(82.9)
|
| Predose Cycle 5 Day 1 |
115
(81.8)
|
| Predose Cycle 6 Day 1 |
119
(68.9)
|
| Title | Number of Participants With Serum Anti-Necitumumab Antibody Assessment (Immunogenicity) |
|---|---|
| Description | A participant was considered to have an anti-Necitumumab antibody response if anti-drug antibodies (ADA) were confirmed positive. Treatment emergent antibodies were defined as any anti-Necitumumab antibody titer equal to or greater than 4-fold the participant's baseline titer. |
| Time Frame | Baseline to Study Completion (Up to 31.6 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of necitumumab and had evaluable antibody data. |
| Arm/Group Title | Necitumumab + Pemextrexed + Cisplatin |
|---|---|
| Arm/Group Description | Necitumumab + Pemetrexed + Cisplatin Necitumumab: 800 mg (absolute dose) on Days 1 and 8 of every 3-week cycle, administered as an I.V. infusion Pemetrexed: 500 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles |
| Measure Participants | 301 |
| 1 Positive Titer |
37
11.7%
|
| Antibodies Detected |
18
5.7%
|
| Title | Mean Change From Baseline in Patient Reported Outcomes (PRO) Using the European Quality of Life-5 Dimensions (EQ-5D) |
|---|---|
| Description | The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a three level scale 1-3 (no problem, some problems, and major problems). These combinations of attributes were converted into a weighted health-state Index Score according to the United Kingdom (UK) population-based algorithm. The possible values for the Index Score ranged from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension). |
| Time Frame | Baseline, Cycle 6 (Cycle = 3 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who had evaluable baseline and postbaseline EQ-5D data. |
| Arm/Group Title | Necitumumab + Pemetrexed + Cisplatin | Pemetrexed + Cisplatin |
|---|---|---|
| Arm/Group Description | Necitumumab + Pemetrexed + Cisplatin Necitumumab: 800 mg (absolute dose) on Days 1 and 8 of every 3-week cycle, administered as an I.V. infusion Pemetrexed: 500 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles | Pemetrexed + Cisplatin Pemetrexed: 500 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles |
| Measure Participants | 143 | 147 |
| Mean (Standard Deviation) [units on a scale] |
0.0419
(0.28230)
|
0.0478
(0.22645)
|
| Title | Mean Change From Baseline in PRO as Measured Using the Lung Cancer Symptom Scale (LCSS) |
|---|---|
| Description | The LCSS consisted of 9 items: 6 items focused on lung cancer symptoms [loss of appetite, fatigue, cough, dyspnea (shortness of breath), hemoptysis (blood in sputum), and pain] and 3 items were global items (symptom distress, interference with activity level, and global quality of life). Participant responses to each item were measured using visual analogue scales (VAS) with 100-mm lines. A higher score for any item represented a higher level of symptoms/problems. Scores for each of the reported categories ranged from 0 (for best outcome) to 100 (for worst outcome). The Average Symptom Burden Index (ASBI) was the mean of the 6 symptom items of the LCSS, and the Total LCSS was the mean of all 9 LCSS items. ASBI and Total LCSS were not computed for a participant if he/she had 1 or more missing values for the 6 and 9 items, respectively. |
| Time Frame | Baseline, Cycle 6 (Cycle =3 Weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who had evaluable baseline and postbaseline LCSS data. |
| Arm/Group Title | Necitumumab + Pemetrexed + Cisplatin | Pemetrexed + Cisplatin |
|---|---|---|
| Arm/Group Description | Necitumumab + Pemetrexed + Cisplatin Necitumumab: 800 mg (absolute dose) on Days 1 and 8 of every 3-week cycle, administered as an I.V. infusion Pemetrexed: 500 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles | Pemetrexed + Cisplatin Pemetrexed: 500 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles |
| Measure Participants | 315 | 318 |
| Loss of Appetite |
4.6
(46.18)
|
0.6
(27.52)
|
| Fatigue |
4.5
(31.24)
|
1.6
(28.75)
|
| Cough |
-9.1
(31.08)
|
-10.3
(27.88)
|
| Dyspnea |
-2.8
(26.32)
|
-1.5
(23.67)
|
| Hemoptysis |
-1.1
(11.92)
|
-1.1
(7.81)
|
| Pain |
-4.2
(27.22)
|
-7.1
(26.64)
|
| Overall Symptoms |
-3.1
(31.22)
|
-7.4
(27.11)
|
| Quality of Life |
2.5
(26.01)
|
-3.3
(24.91)
|
| Interference |
3.2
(27.15)
|
-4.0
(31.39)
|
| Average Symptom Burden Index (ASBI) |
-0.9
(18.35)
|
-3.1
(13.11)
|
| LCSS Total Score |
0.1
(17.59)
|
-4.3
(13.90)
|
| Title | Epidermal Growth Factor Hormone (EGFR) Protein Expression Measured by Immunohistochemistry (IHC) |
|---|---|
| Description | EGFR IHC H-score = weighted sum of % 1+ cells, twice % 2+ cells, and three times % 3+ cells. IHC H-score criteria assesses participants with a low EGFR expression defined by a H-score cutoff value of < 200 and participants with a high EGFR expression defined by a H-score of cutoff value of >=200. |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Translational research population included all participants who: (1) received at least one dose of study drug; (2) had a valid non-missing result for EGFR H-Score; and (3) were enrolled for more than 2 cycles prior to the decision to terminate enrollment. |
| Arm/Group Title | Necitumumab + Pemetrexed + Cisplatin | Pemetrexed + Cisplatin |
|---|---|---|
| Arm/Group Description | Necitumumab + Pemetrexed + Cisplatin Necitumumab: 800 mg (absolute dose) on Days 1 and 8 of every 3-week cycle, administered as an I.V. infusion Pemetrexed: 500 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles | Pemetrexed + Cisplatin Pemetrexed: 500 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles |
| Measure Participants | 245 | 245 |
| H-score <200 |
69.06
(64.68)
|
66.23
(64.15)
|
| H-score >=200 |
259.35
(27.65)
|
256.26
(29.10)
|
| Title | Percentage of Participants With EGFR Measured by IHC |
|---|---|
| Description | EGFR IHC H-score = weighted sum of % 1+ cells, twice % 2+ cells, and three times % 3+ cells. IHC H-score criteria assesses participants with a low EGFR expression defined by a H-score cutoff value of < 200 and participants with a high EGFR expression defined by a H-score of cutoff value of >=200. |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Translational research population included all participants who: (1) received at least one dose of study drug; (2) had a valid non-missing result for EGFR H-Score; and (3) were enrolled for more than 2 cycles prior to the decision to terminate enrollment |
| Arm/Group Title | Necitumumab + Pemetrexed + Cisplatin | Pemetrexed + Cisplatin |
|---|---|---|
| Arm/Group Description | Necitumumab + Pemetrexed + Cisplatin Necitumumab: 800 mg (absolute dose) on Days 1 and 8 of every 3-week cycle, administered as an I.V. infusion Pemetrexed: 500 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles | Pemetrexed + Cisplatin Pemetrexed: 500 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles |
| Measure Participants | 245 | 245 |
| H-score <200 |
58.8
18.7%
|
59.6
18.7%
|
| H-score >=200 |
41.2
13.1%
|
40.4
12.7%
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly | |||
| Arm/Group Title | Necitumumab+Pemetrexed+Cisplatin | Pemetrexed+Cisplatin | ||
| Arm/Group Description | Necitumumab + Pemetrexed + Cisplatin Necitumumab: 800 mg (absolute dose) on Days 1 and 8 of every 3-week cycle Pemetrexed: 500 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles | Pemetrexed + Cisplatin Pemetrexed: 500 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles Cisplatin: 75 mg/m2 I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles | ||
All Cause Mortality |
||||
| Necitumumab+Pemetrexed+Cisplatin | Pemetrexed+Cisplatin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 236/304 (77.6%) | 246/312 (78.8%) | ||
Serious Adverse Events |
||||
| Necitumumab+Pemetrexed+Cisplatin | Pemetrexed+Cisplatin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 158/304 (52%) | 130/312 (41.7%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 12/304 (3.9%) | 15 | 13/312 (4.2%) | 18 |
| Febrile neutropenia | 1/304 (0.3%) | 1 | 2/312 (0.6%) | 2 |
| Granulocytopenia | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Leukopenia | 5/304 (1.6%) | 5 | 8/312 (2.6%) | 8 |
| Neutropenia | 9/304 (3%) | 9 | 5/312 (1.6%) | 5 |
| Pancytopenia | 1/304 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Splenic infarction | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Thrombocytopenia | 8/304 (2.6%) | 9 | 5/312 (1.6%) | 6 |
| Cardiac disorders | ||||
| Acute myocardial infarction | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Angina pectoris | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Arrhythmia supraventricular | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Atrial fibrillation | 2/304 (0.7%) | 2 | 2/312 (0.6%) | 2 |
| Atrial flutter | 2/304 (0.7%) | 2 | 0/312 (0%) | 0 |
| Cardiac failure | 2/304 (0.7%) | 2 | 0/312 (0%) | 0 |
| Cardiac tamponade | 2/304 (0.7%) | 2 | 0/312 (0%) | 0 |
| Cardio-respiratory arrest | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Cardiomyopathy | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Cardiopulmonary failure | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Myocardial infarction | 1/304 (0.3%) | 2 | 1/312 (0.3%) | 1 |
| Pericardial effusion | 3/304 (1%) | 3 | 2/312 (0.6%) | 2 |
| Sinus tachycardia | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Tachycardia | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Ear and labyrinth disorders | ||||
| Vertigo | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Dental caries | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Diarrhoea | 10/304 (3.3%) | 11 | 5/312 (1.6%) | 5 |
| Duodenal ulcer | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Duodenal ulcer haemorrhage | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Dysphagia | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Enterocolitis | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Gastrointestinal disorder | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Ileus paralytic | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Inguinal hernia | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Intestinal infarction | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Intestinal perforation | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Intra-abdominal haemorrhage | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Large intestine perforation | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Nausea | 8/304 (2.6%) | 12 | 6/312 (1.9%) | 6 |
| Oesophageal ulcer | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Oesophagitis | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Pneumatosis intestinalis | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Rectal haemorrhage | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Stomatitis | 1/304 (0.3%) | 1 | 3/312 (1%) | 4 |
| Volvulus | 1/304 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Vomiting | 9/304 (3%) | 10 | 7/312 (2.2%) | 7 |
| General disorders | ||||
| Asthenia | 8/304 (2.6%) | 11 | 2/312 (0.6%) | 3 |
| Chest pain | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Death | 3/304 (1%) | 3 | 1/312 (0.3%) | 1 |
| Fatigue | 8/304 (2.6%) | 10 | 7/312 (2.2%) | 7 |
| General physical health deterioration | 6/304 (2%) | 7 | 4/312 (1.3%) | 5 |
| Mucosal inflammation | 4/304 (1.3%) | 4 | 0/312 (0%) | 0 |
| Multi-organ failure | 2/304 (0.7%) | 2 | 0/312 (0%) | 0 |
| Oedema peripheral | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Performance status decreased | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Pyrexia | 4/304 (1.3%) | 4 | 0/312 (0%) | 0 |
| Systemic inflammatory response syndrome | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Hepatobiliary disorders | ||||
| Biliary colic | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Cholecystitis | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Hepatic failure | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Infections and infestations | ||||
| Abscess limb | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Bronchitis | 1/304 (0.3%) | 1 | 2/312 (0.6%) | 2 |
| Device related infection | 2/304 (0.7%) | 2 | 0/312 (0%) | 0 |
| Diverticulitis | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Erysipelas | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Gastrointestinal infection | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Hepatitis b | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Herpes dermatitis | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Herpes oesophagitis | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Infection | 2/304 (0.7%) | 2 | 2/312 (0.6%) | 2 |
| Intestinal gangrene | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Lung infection | 2/304 (0.7%) | 2 | 1/312 (0.3%) | 2 |
| Neutropenic sepsis | 3/304 (1%) | 3 | 0/312 (0%) | 0 |
| Oral candidiasis | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Peritoneal infection | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Pneumonia | 14/304 (4.6%) | 14 | 6/312 (1.9%) | 7 |
| Pyelonephritis | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Respiratory tract infection | 1/304 (0.3%) | 1 | 3/312 (1%) | 3 |
| Sepsis | 4/304 (1.3%) | 4 | 0/312 (0%) | 0 |
| Septic shock | 1/304 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Skin bacterial infection | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Skin infection | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Staphylococcal infection | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Staphylococcal sepsis | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Urinary tract infection | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Drug administration error | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Femur fracture | 1/304 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Hip fracture | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Incorrect dose administered | 2/304 (0.7%) | 3 | 2/312 (0.6%) | 2 |
| Lumbar vertebral fracture | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Medication error | 6/304 (2%) | 6 | 2/312 (0.6%) | 2 |
| Procedural pain | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Suture rupture | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Investigations | ||||
| International normalised ratio increased | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Weight decreased | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Anorexia | 6/304 (2%) | 6 | 3/312 (1%) | 3 |
| Cachexia | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Dehydration | 4/304 (1.3%) | 4 | 5/312 (1.6%) | 8 |
| Electrolyte imbalance | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Fluid retention | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Hyperglycaemia | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Hyperkalaemia | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Hyperuricaemia | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Hypocalcaemia | 3/304 (1%) | 4 | 0/312 (0%) | 0 |
| Hypokalaemia | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Hypomagnesaemia | 3/304 (1%) | 3 | 1/312 (0.3%) | 1 |
| Hyponatraemia | 0/304 (0%) | 0 | 2/312 (0.6%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 1/304 (0.3%) | 1 | 2/312 (0.6%) | 2 |
| Back pain | 2/304 (0.7%) | 2 | 1/312 (0.3%) | 1 |
| Bone pain | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Flank pain | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Musculoskeletal chest pain | 3/304 (1%) | 3 | 0/312 (0%) | 0 |
| Musculoskeletal pain | 0/304 (0%) | 0 | 2/312 (0.6%) | 2 |
| Myalgia | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Pain in extremity | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Pathological fracture | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Cancer pain | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Malignant pleural effusion | 1/304 (0.3%) | 2 | 1/312 (0.3%) | 1 |
| Metastases to central nervous system | 5/304 (1.6%) | 5 | 0/312 (0%) | 0 |
| Metastatic pain | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Non-small cell lung cancer | 24/304 (7.9%) | 24 | 10/312 (3.2%) | 10 |
| Tumour pain | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Nervous system disorders | ||||
| Cerebral infarction | 1/304 (0.3%) | 1 | 2/312 (0.6%) | 2 |
| Cerebral ischaemia | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Cerebrovascular accident | 1/304 (0.3%) | 1 | 4/312 (1.3%) | 5 |
| Convulsion | 5/304 (1.6%) | 5 | 0/312 (0%) | 0 |
| Dizziness | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Dizziness postural | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Hemiparesis | 0/304 (0%) | 0 | 2/312 (0.6%) | 2 |
| Hypotonia | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Ischaemic stroke | 2/304 (0.7%) | 2 | 0/312 (0%) | 0 |
| Migraine | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Paraesthesia | 1/304 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Spinal cord compression | 0/304 (0%) | 0 | 2/312 (0.6%) | 2 |
| Syncope | 3/304 (1%) | 3 | 0/312 (0%) | 0 |
| Psychiatric disorders | ||||
| Agitation | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Confusional state | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Depression | 0/304 (0%) | 0 | 1/312 (0.3%) | 2 |
| Renal and urinary disorders | ||||
| Nephropathy toxic | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Renal failure | 4/304 (1.3%) | 5 | 6/312 (1.9%) | 7 |
| Renal failure acute | 3/304 (1%) | 3 | 1/312 (0.3%) | 1 |
| Renal impairment | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute pulmonary oedema | 1/304 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Acute respiratory distress syndrome | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Acute respiratory failure | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Chronic obstructive pulmonary disease | 1/304 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Cough | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Dyspnoea | 8/304 (2.6%) | 8 | 5/312 (1.6%) | 8 |
| Epistaxis | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Haemoptysis | 1/304 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Interstitial lung disease | 0/304 (0%) | 0 | 1/312 (0.3%) | 2 |
| Pleural effusion | 1/304 (0.3%) | 2 | 3/312 (1%) | 3 |
| Pneumonitis | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Pneumothorax | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Pulmonary artery thrombosis | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Pulmonary embolism | 13/304 (4.3%) | 13 | 11/312 (3.5%) | 11 |
| Pulmonary haemorrhage | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Pulmonary oedema | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Respiratory failure | 5/304 (1.6%) | 5 | 2/312 (0.6%) | 2 |
| Skin and subcutaneous tissue disorders | ||||
| Rash | 5/304 (1.6%) | 5 | 0/312 (0%) | 0 |
| Rash maculo-papular | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Toxic skin eruption | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Urticaria | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Surgical and medical procedures | ||||
| Analgesic therapy | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Vascular disorders | ||||
| Aortic aneurysm rupture | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Arterial stenosis limb | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Arterial thrombosis limb | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Circulatory collapse | 0/304 (0%) | 0 | 2/312 (0.6%) | 2 |
| Deep vein thrombosis | 5/304 (1.6%) | 5 | 1/312 (0.3%) | 1 |
| Embolism | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Hypertension | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Orthostatic hypotension | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
| Peripheral embolism | 2/304 (0.7%) | 2 | 0/312 (0%) | 0 |
| Peripheral ischaemia | 2/304 (0.7%) | 2 | 0/312 (0%) | 0 |
| Poor venous access | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Subclavian vein thrombosis | 2/304 (0.7%) | 2 | 0/312 (0%) | 0 |
| Superior vena caval occlusion | 0/304 (0%) | 0 | 1/312 (0.3%) | 1 |
| Thrombosis | 1/304 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Venous thrombosis limb | 1/304 (0.3%) | 1 | 0/312 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Necitumumab+Pemetrexed+Cisplatin | Pemetrexed+Cisplatin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 296/304 (97.4%) | 303/312 (97.1%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 72/304 (23.7%) | 155 | 91/312 (29.2%) | 200 |
| Leukopenia | 45/304 (14.8%) | 92 | 36/312 (11.5%) | 61 |
| Lymphopenia | 16/304 (5.3%) | 53 | 17/312 (5.4%) | 26 |
| Neutropenia | 92/304 (30.3%) | 179 | 99/312 (31.7%) | 217 |
| Thrombocytopenia | 22/304 (7.2%) | 43 | 23/312 (7.4%) | 42 |
| Ear and labyrinth disorders | ||||
| Tinnitus | 15/304 (4.9%) | 18 | 16/312 (5.1%) | 18 |
| Eye disorders | ||||
| Conjunctivitis | 31/304 (10.2%) | 46 | 6/312 (1.9%) | 6 |
| Lacrimation increased | 4/304 (1.3%) | 4 | 17/312 (5.4%) | 17 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 19/304 (6.3%) | 25 | 15/312 (4.8%) | 15 |
| Abdominal pain upper | 26/304 (8.6%) | 36 | 25/312 (8%) | 29 |
| Constipation | 91/304 (29.9%) | 133 | 83/312 (26.6%) | 124 |
| Diarrhoea | 90/304 (29.6%) | 148 | 51/312 (16.3%) | 78 |
| Dyspepsia | 16/304 (5.3%) | 21 | 18/312 (5.8%) | 28 |
| Nausea | 174/304 (57.2%) | 392 | 183/312 (58.7%) | 403 |
| Stomatitis | 30/304 (9.9%) | 41 | 12/312 (3.8%) | 22 |
| Vomiting | 105/304 (34.5%) | 213 | 104/312 (33.3%) | 180 |
| General disorders | ||||
| Asthenia | 88/304 (28.9%) | 192 | 68/312 (21.8%) | 146 |
| Fatigue | 87/304 (28.6%) | 164 | 95/312 (30.4%) | 171 |
| Mucosal inflammation | 50/304 (16.4%) | 104 | 27/312 (8.7%) | 36 |
| Non-cardiac chest pain | 11/304 (3.6%) | 16 | 16/312 (5.1%) | 22 |
| Oedema peripheral | 40/304 (13.2%) | 52 | 41/312 (13.1%) | 51 |
| Pyrexia | 46/304 (15.1%) | 57 | 22/312 (7.1%) | 32 |
| Infections and infestations | ||||
| Oral candidiasis | 18/304 (5.9%) | 22 | 5/312 (1.6%) | 5 |
| Paronychia | 28/304 (9.2%) | 67 | 0/312 (0%) | 0 |
| Urinary tract infection | 19/304 (6.3%) | 21 | 16/312 (5.1%) | 21 |
| Investigations | ||||
| Blood creatinine increased | 21/304 (6.9%) | 34 | 18/312 (5.8%) | 23 |
| Weight decreased | 39/304 (12.8%) | 53 | 24/312 (7.7%) | 28 |
| Metabolism and nutrition disorders | ||||
| Anorexia | 110/304 (36.2%) | 174 | 97/312 (31.1%) | 171 |
| Fluid retention | 17/304 (5.6%) | 39 | 12/312 (3.8%) | 22 |
| Hyperglycaemia | 16/304 (5.3%) | 34 | 10/312 (3.2%) | 15 |
| Hypocalcaemia | 30/304 (9.9%) | 51 | 13/312 (4.2%) | 16 |
| Hypokalaemia | 20/304 (6.6%) | 34 | 23/312 (7.4%) | 33 |
| Hypomagnesaemia | 75/304 (24.7%) | 185 | 36/312 (11.5%) | 66 |
| Hyponatraemia | 23/304 (7.6%) | 36 | 20/312 (6.4%) | 30 |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 33/304 (10.9%) | 40 | 20/312 (6.4%) | 24 |
| Musculoskeletal pain | 19/304 (6.3%) | 26 | 15/312 (4.8%) | 21 |
| Pain in extremity | 18/304 (5.9%) | 22 | 17/312 (5.4%) | 19 |
| Nervous system disorders | ||||
| Dizziness | 38/304 (12.5%) | 52 | 26/312 (8.3%) | 37 |
| Dysgeusia | 21/304 (6.9%) | 27 | 32/312 (10.3%) | 43 |
| Headache | 30/304 (9.9%) | 41 | 27/312 (8.7%) | 32 |
| Paraesthesia | 16/304 (5.3%) | 20 | 8/312 (2.6%) | 9 |
| Psychiatric disorders | ||||
| Depression | 18/304 (5.9%) | 20 | 10/312 (3.2%) | 11 |
| Insomnia | 17/304 (5.6%) | 23 | 15/312 (4.8%) | 20 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 56/304 (18.4%) | 75 | 48/312 (15.4%) | 59 |
| Dyspnoea | 46/304 (15.1%) | 62 | 41/312 (13.1%) | 52 |
| Epistaxis | 21/304 (6.9%) | 30 | 9/312 (2.9%) | 9 |
| Haemoptysis | 21/304 (6.9%) | 30 | 10/312 (3.2%) | 12 |
| Productive cough | 16/304 (5.3%) | 17 | 7/312 (2.2%) | 9 |
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 29/304 (9.5%) | 31 | 18/312 (5.8%) | 20 |
| Dermatitis acneiform | 42/304 (13.8%) | 119 | 0/312 (0%) | 0 |
| Dry skin | 43/304 (14.1%) | 62 | 11/312 (3.5%) | 13 |
| Hirsutism | 5/95 (5.3%) | 5 | 0/107 (0%) | 0 |
| Pruritus | 31/304 (10.2%) | 48 | 8/312 (2.6%) | 9 |
| Rash | 125/304 (41.1%) | 346 | 20/312 (6.4%) | 23 |
| Rash generalised | 28/304 (9.2%) | 62 | 5/312 (1.6%) | 5 |
| Vascular disorders | ||||
| Hypertension | 17/304 (5.6%) | 24 | 29/312 (9.3%) | 41 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 800-545-5979 |
| ClinicalTrials.gov@lilly.com |
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00982111
Other Study ID Numbers:
- 13908
- 2009-012574-12
- CP11-0805
- I4X-IE-JFCB
First Posted:
Sep 22, 2009
Last Update Posted:
Jan 11, 2022
Last Verified:
Dec 1, 2021