A Study of Gemcitabine-Cisplatin Chemotherapy Plus Necitumumab in the First-Line Treatment of Participants With Squamous Lung Cancer

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01788566
• Collaborator: (none)
• Enrollment: 61
• Locations: 17
• Arm: 1
• Duration (Months): 33
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to see how participants with late stage lung cancer do on gemcitabine-cisplatin chemotherapy plus necitumumab. The study will also see how safe the drugs are in combination and to see how long the medicine stays in the body. The study will last approximately 2 years.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Drug: Necitumumab; Drug: Gemcitabine; Drug: Cisplatin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 61 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single-Arm, Multicenter, Open-Label, Phase 2 Study of Gemcitabine-Cisplatin Chemotherapy Plus Necitumumab (IMC-11F8) in the First-Line Treatment of Patients With Stage IV Squamous Non-Small Cell Lung Cancer (NSCLC)
• Study Start Date: Mar 1, 2013
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gemcitabine + Cisplatin + Necitumumab Necitumumab administered intravenously (IV) 800 milligram (mg) on Days 1 and 8 of each 3-week cycle. Gemcitabine administered IV at 1250 milligram per square meter (mg/m^2) on Days 1 and 8 of each 3 week cycle for a maximum of 6 cycles. Cisplatin administered IV at 75 mg/m^2 on Day 1 of each 3 week cycle for a maximum of 6 cycles.	Drug: Necitumumab; Administered IV; Other Names: IMC-11F8 LY3012211 Portrazza® ; Drug: Gemcitabine; Administered IV; Other Names: Gemzar® LY188011 ; Drug: Cisplatin; Administered IV

Outcome Measures

Primary Outcome Measures

1. 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 17 Months)]

   ORR is confirmed best overall tumor response of CR or PR. According to RECIST v1.1, 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; CR was defined as the disappearance of all target and non-target lesions. Percentage of participants was calculated as: total number of participants with a best tumor response of PR or CR among participants counted in the denominator/total number of participants treated with any amount of study drug, who has a complete radiographic assessment at baseline, and who has at least 1 complete radiographic assessment at postbaseline x 100%.

Secondary Outcome Measures

1. Overall Survival (OS) [Baseline to Death from Any Cause (up to 17 Months)]

   Overall survival (OS) duration is defined from the date of first dose of study drug to the date of death from any cause. OS was estimated by the Kaplan-Meier method. For participants who were not known to have died as of the data cut-off date, OS was censored at the date of last contact prior to the data cutoff date.

2. Progression Free Survival (PFS) [Baseline to Measured Progressive Disease or Death from Any Cause (up to 17 Months)]

   PFS is defined as the time from the date of first dose of study drug until objective progressive disease (PD) or death for any cause. According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), PD was at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the 20% relative increase, the sum must have also demonstrated an absolute increase of at least 5 millimeters (mm). The appearance of 1 or more new lesions was also considered progression. For participants not known to have died as of the data cut-off date and who do not have objective PD, PFS will be censored at the date of the last complete radiographic assessment.

3. Number of Participants Who Achieve Best Overall Disease Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) [Disease Control Rate (DCR)] [Baseline to Measured Progressive Disease or Participants Stops Study (up to 17 Months)]

   DCR is best overall response of SD, PR or CR. According to RECIST v1.1, 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; CR was defined as the disappearance of all target and non-target lesions. SD was neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started. Percentage of participants who achieved disease control = (those participants counted in the denominator with a best tumor response of SD, PR, or CR)/(the same denominator as for ORR)*100.

4. Percent Change in Tumor Size (CTS) [Baseline until Measured Progressive Disease (up to 17 Months)]

   CTS is defined as maximum percent improvement from baseline in the sum of target lesions.

5. Pharmacokinetics (PK): Minimum (Cmin) Maximum Concentration (Cmax) of Necitumumab [Predose Cycle 1 Day 8; Cycle 2 through 6 Day 1; End of Infusion (EOI) Cycle 1, 3, 5 Day 1]

   Pre-infusion Minimum Concentration (Cmin) and post-infusion (Cmax) necitumumab serum concentration

6. Number of Participants With Anti-Necitumumab Antibodies [Baseline up to 30 Days Post Last Infusion (up to 17 Months)]

   A participant was considered to have an anti-necitumumab antibody response if anti-drug antibodies (ADA) were detected at any time point. Treatment emergent antibodies were defined as any anti-necitumumab antibody titer equal to or greater than 4-fold the participant's baseline titer.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically confirmed squamous Non-small Cell Lung Cancer (NSCLC)

• Stage IV disease at time of study entry based on American Joint Committee on Cancer 7th edition

• Measurable disease at time of study entry as defined by Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1

• Required to have a performance status (PS) 0-1

Exclusion Criteria:

• Nonsquamous NSCLC

• Prior anticancer therapy with monoclonal antibodies, signal transduction inhibitors, or any therapies targeting the epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), or VEGF receptor

• Previous chemotherapy for NSCLC

• Major surgery or received any investigational therapy in the 4 weeks prior to study enrollment

• Chest irradiation within 12 weeks prior to randomization (except palliative irradiation of bone lesions, which is allowed)

• 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Birmingham	Alabama	United States	35294
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Deerfield Beach	Florida	United States	33442
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Farmington Hills	Michigan	United States	48334
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Calgary	Alberta	Canada	T2N 4N2
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hamilton	Ontario	Canada	L8V 5C2
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	London	Ontario	Canada	N6A 4L6
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Montreal	Quebec	Canada	H3A 1A1
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Paris		France	75970
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Durango		Mexico	34000
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Guadalajara		Mexico	44200
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Breda		Netherlands	4818 CK
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Eindhoven		Netherlands	5623 EJ
13	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Madrid		Spain	28041
14	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Majadahonda		Spain	28222
15	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sevilla		Spain	41014
16	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Taichung		Taiwan	404
17	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Taipei		Taiwan	112

Sponsors and Collaborators

• Eli Lilly and Company

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: NCT01788566
• Other Study ID Numbers: 14789; I4X-MC-JFCK
• First Posted: Feb 11, 2013
• Last Update Posted: Jun 27, 2016
• Last Verified: May 1, 2016

• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Gemcitabine; Necitumumab

Study Results

Participant Flow

Arm/Group Title	Gemcitabine + Cisplatin + Necitumumab
Arm/Group Description	Necitumumab administered intravenously (IV) 800 milligram (mg) on Days 1 and 8 of each 3-week cycle. Gemcitabine administered IV at 1250 milligram per square meter (mg/m^2) on Days 1 and 8 of each 3 week cycle for a maximum of 6 cycles. Cisplatin administered IV at 75 mg/m^2 on Day 1 of each 3 week cycle for a maximum of 6 cycles.
Period Title: Overall Study
STARTED	61
COMPLETED	53
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	Gemcitabine + Cisplatin + Necitumumab
Arm/Group Description	Necitumumab administered intravenously (IV) 800 milligram (mg) on Days 1 and 8 of each 3-week cycle. Gemcitabine administered IV at 1250 milligram per square meter (mg/m^2) on Days 1 and 8 of each 3 week cycle for a maximum of 6 cycles. Cisplatin administered IV at 75 mg/m^2 on Day 1 of each 3 week cycle for a maximum of 6 cycles.
Overall Participants	61
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	28 45.9%
>=65 years	33 54.1%
Sex: Female, Male (Count of Participants)
Female	12 19.7%
Male	49 80.3%
Race/Ethnicity, Customized (Number) [Number]
White	48 78.7%
Asian	11 18%
Black or African American	1 1.6%
Missing	1 1.6%
Region of Enrollment (participants) [Number]
Canada	5 8.2%
Netherlands	5 8.2%
United States	11 18%
Taiwan	8 13.1%
Mexico	1 1.6%
France	3 4.9%
Spain	25 41%
Korea, Republic of	3 4.9%

Outcome Measures

1. Primary Outcome

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 v1.1, 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; CR was defined as the disappearance of all target and non-target lesions. Percentage of participants was calculated as: total number of participants with a best tumor response of PR or CR among participants counted in the denominator/total number of participants treated with any amount of study drug, who has a complete radiographic assessment at baseline, and who has at least 1 complete radiographic assessment at postbaseline x 100%.
Time Frame	Baseline to Measured Progressive Disease (up to 17 Months)

Outcome Measure Data

Analysis Population Description

All participants who received any amount of study treatment and had evaluable baseline and postbaseline data for radiographic assessment.

Arm/Group Title	Gemcitabine + Cisplatin + Necitumumab
Arm/Group Description	Necitumumab administered intravenously (IV) 800 milligram (mg) on Days 1 and 8 of each 3-week cycle. Gemcitabine administered IV at 1250 milligram per square meter (mg/m^2) on Days 1 and 8 of each 3 week cycle for a maximum of 6 cycles. Cisplatin administered IV at 75 mg/m^2 on Day 1 of each 3 week cycle for a maximum of 6 cycles.
Measure Participants	54
Number (95% Confidence Interval) [Percentage of participants]	48.1 78.9%

2. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival (OS) duration is defined from the date of first dose of study drug to the date of death from any cause. OS was estimated by the Kaplan-Meier method. For participants who were not known to have died as of the data cut-off date, OS was censored at the date of last contact prior to the data cutoff date.
Time Frame	Baseline to Death from Any Cause (up to 17 Months)

Outcome Measure Data

Analysis Population Description

All participants who received any amount of study treatment. Participants censored=34.

Arm/Group Title	Gemcitabine + Cisplatin + Necitumumab
Arm/Group Description	Necitumumab administered intravenously (IV) 800 milligram (mg) on Days 1 and 8 of each 3-week cycle. Gemcitabine administered IV at 1250 milligram per square meter (mg/m^2) on Days 1 and 8 of each 3 week cycle for a maximum of 6 cycles. Cisplatin administered IV at 75 mg/m^2 on Day 1 of each 3 week cycle for a maximum of 6 cycles.
Measure Participants	61
Median (95% Confidence Interval) [months]	11.7

3. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS is defined as the time from the date of first dose of study drug until objective progressive disease (PD) or death for any cause. According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), PD was at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the 20% relative increase, the sum must have also demonstrated an absolute increase of at least 5 millimeters (mm). The appearance of 1 or more new lesions was also considered progression. For participants not known to have died as of the data cut-off date and who do not have objective PD, PFS will be censored at the date of the last complete radiographic assessment.
Time Frame	Baseline to Measured Progressive Disease or Death from Any Cause (up to 17 Months)

Outcome Measure Data

Analysis Population Description

All participants who received any quantity of study treatment.

Arm/Group Title	Gemcitabine + Cisplatin + Necitumumab
Arm/Group Description	Necitumumab administered intravenously (IV) 800 milligram (mg) on Days 1 and 8 of each 3-week cycle. Gemcitabine administered IV at 1250 milligram per square meter (mg/m^2) on Days 1 and 8 of each 3 week cycle for a maximum of 6 cycles. Cisplatin administered IV at 75 mg/m^2 on Day 1 of each 3 week cycle for a maximum of 6 cycles.
Measure Participants	61
Median (95% Confidence Interval) [months]	5.6

4. Secondary Outcome

Title	Number of Participants Who Achieve Best Overall Disease Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) [Disease Control Rate (DCR)]
Description	DCR is best overall response of SD, PR or CR. According to RECIST v1.1, 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; CR was defined as the disappearance of all target and non-target lesions. SD was neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started. Percentage of participants who achieved disease control = (those participants counted in the denominator with a best tumor response of SD, PR, or CR)/(the same denominator as for ORR)*100.
Time Frame	Baseline to Measured Progressive Disease or Participants Stops Study (up to 17 Months)

Outcome Measure Data

Analysis Population Description

All participants who received any quantity of study treatment and had evaluable baseline and postbaseline data for radiographic assessment.

Arm/Group Title	Gemcitabine + Cisplatin + Necitumumab
Arm/Group Description	Necitumumab administered intravenously (IV) 800 milligram (mg) on Days 1 and 8 of each 3-week cycle. Gemcitabine administered IV at 1250 milligram per square meter (mg/m^2) on Days 1 and 8 of each 3 week cycle for a maximum of 6 cycles. Cisplatin administered IV at 75 mg/m^2 on Day 1 of each 3 week cycle for a maximum of 6 cycles.
Measure Participants	54
Number (95% Confidence Interval) [percentage of participants]	81.5 133.6%

5. Secondary Outcome

Title	Percent Change in Tumor Size (CTS)
Description	CTS is defined as maximum percent improvement from baseline in the sum of target lesions.
Time Frame	Baseline until Measured Progressive Disease (up to 17 Months)

Outcome Measure Data

Analysis Population Description

All participants who received any quantity of study treatment and had evaluable baseline and postbaseline data for CTS.

Arm/Group Title	Gemcitabine + Cisplatin + Necitumumab
Arm/Group Description	Necitumumab administered intravenously (IV) 800 milligram (mg) on Days 1 and 8 of each 3-week cycle. Gemcitabine administered IV at 1250 milligram per square meter (mg/m^2) on Days 1 and 8 of each 3 week cycle for a maximum of 6 cycles. Cisplatin administered IV at 75 mg/m^2 on Day 1 of each 3 week cycle for a maximum of 6 cycles.
Measure Participants	61
Mean (Standard Deviation) [percent change]	39.68 (21.296)

6. Secondary Outcome

Title	Pharmacokinetics (PK): Minimum (Cmin) Maximum Concentration (Cmax) of Necitumumab
Description	Pre-infusion Minimum Concentration (Cmin) and post-infusion (Cmax) necitumumab serum concentration
Time Frame	Predose Cycle 1 Day 8; Cycle 2 through 6 Day 1; End of Infusion (EOI) Cycle 1, 3, 5 Day 1

Outcome Measure Data

Analysis Population Description

All participants who received any amount of study treatment and had evaluable data for Cmax

Arm/Group Title	Gemcitabine + Cisplatin + Necitumumab
Arm/Group Description	Necitumumab administered intravenously (IV) 800 milligram (mg) on Days 1 and 8 of each 3-week cycle. Gemcitabine administered IV at 1250 milligram per square meter (mg/m^2) on Days 1 and 8 of each 3 week cycle for a maximum of 6 cycles. Cisplatin administered IV at 75 mg/m^2 on Day 1 of each 3 week cycle for a maximum of 6 cycles.
Measure Participants	61
Predose Cycle 1 Day 8	70.8 (36.7)
Predose Cycle 2 Day 1	67.5 (78.0)
Predose Cycle 3 Day 1	106 (36.6)
Predose Cycle 4 Day 1	115 (43.9)
Predose Cycle 5 Day 1	141 (62.3)
Predose Cycle 6 Day 1	126 (34.2)
EOI Cycle 1 Day 1	266 (24.8)
EOI Cycle 3 Day 1	352 (29.5)
EOI Cycle 5 Day 1	360 (29.2)

7. Secondary Outcome

Title	Number of Participants With Anti-Necitumumab Antibodies
Description	A participant was considered to have an anti-necitumumab antibody response if anti-drug antibodies (ADA) were detected at any time point. 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 up to 30 Days Post Last Infusion (up to 17 Months)

Outcome Measure Data

Analysis Population Description

All participants who received any amount of study treatment and had evaluable baseline and postbaseline data for antibodies.

Arm/Group Title	Gemcitabine + Cisplatin + Necitumumab
Arm/Group Description	Necitumumab administered intravenously (IV) 800 milligram (mg) on Days 1 and 8 of each 3-week cycle. Gemcitabine administered IV at 1250 milligram per square meter (mg/m^2) on Days 1 and 8 of each 3 week cycle for a maximum of 6 cycles. Cisplatin administered IV at 75 mg/m^2 on Day 1 of each 3 week cycle for a maximum of 6 cycles.
Measure Participants	61
Number of Participants with 1 Positive Titer	9 14.8%
Treatment Emergent Antibody Positive	4 6.6%
Neutralizing Antibody Detected	3 4.9%

Adverse Events

Arm/Group Title	Gemcitabine + Cisplatin + Necitumumab
Arm/Group Description	Necitumumab administered intravenously (IV) 800 milligram (mg) on Days 1 and 8 of each 3-week cycle. Gemcitabine administered IV at 1250 milligram per square meter (mg/m^2) on Days 1 and 8 of each 3 week cycle for a maximum of 6 cycles. Cisplatin administered IV at 75 mg/m^2 on Day 1 of each 3 week cycle for a maximum of 6 cycles.
All Cause Mortality
	Gemcitabine + Cisplatin + Necitumumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gemcitabine + Cisplatin + Necitumumab
	Affected / at Risk (%)	# Events
Total	33/61 (54.1%)
Blood and lymphatic system disorders
Anaemia	2/61 (3.3%)	2
Febrile neutropenia	3/61 (4.9%)	3
Cardiac disorders
Atrial fibrillation	2/61 (3.3%)	3
Cardiac tamponade	1/61 (1.6%)	1
Myocardial infarction	1/61 (1.6%)	1
Gastrointestinal disorders
Diarrhoea	1/61 (1.6%)	2
Duodenal perforation	1/61 (1.6%)	1
Enteritis	1/61 (1.6%)	1
Gastric perforation	1/61 (1.6%)	1
Intestinal ischaemia	1/61 (1.6%)	1
Stomatitis	1/61 (1.6%)	1
General disorders
Chest pain	2/61 (3.3%)	2
Fatigue	2/61 (3.3%)	2
Malaise	2/61 (3.3%)	3
Pyrexia	2/61 (3.3%)	2
Infections and infestations
Bronchitis	1/61 (1.6%)	1
Catheter site abscess	1/61 (1.6%)	1
Clostridium difficile infection	1/61 (1.6%)	2
Diverticulitis	1/61 (1.6%)	2
Neutropenic sepsis	1/61 (1.6%)	1
Pneumonia	4/61 (6.6%)	4
Pneumonia haemophilus	1/61 (1.6%)	1
Pseudomembranous colitis	1/61 (1.6%)	1
Respiratory tract infection	2/61 (3.3%)	2
Sepsis	1/61 (1.6%)	1
Upper respiratory tract infection	1/61 (1.6%)	1
Urosepsis	1/61 (1.6%)	1
Injury, poisoning and procedural complications
Accidental overdose	1/61 (1.6%)	1
Pulmonary radiation injury	1/61 (1.6%)	1
Metabolism and nutrition disorders
Decreased appetite	1/61 (1.6%)	1
Dehydration	1/61 (1.6%)	1
Hypercalcaemia	1/61 (1.6%)	2
Hypomagnesaemia	2/61 (3.3%)	2
Hyponatraemia	1/61 (1.6%)	1
Musculoskeletal and connective tissue disorders
Flank pain	1/61 (1.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	1/61 (1.6%)	1
Tumour associated fever	1/61 (1.6%)	1
Nervous system disorders
Ischaemic stroke	1/61 (1.6%)	2
Psychiatric disorders
Anxiety	1/61 (1.6%)	1
Conduct disorder	1/61 (1.6%)	1
Confusional state	1/61 (1.6%)	1
Renal and urinary disorders
Haematuria	1/61 (1.6%)	1
Respiratory, thoracic and mediastinal disorders
Acute interstitial pneumonitis	1/61 (1.6%)	1
Acute respiratory failure	1/61 (1.6%)	1
Atelectasis	1/61 (1.6%)	1
Chronic obstructive pulmonary disease	1/61 (1.6%)	1
Dyspnoea	1/61 (1.6%)	1
Haemoptysis	1/61 (1.6%)	1
Pulmonary embolism	1/61 (1.6%)	1
Pulmonary haemorrhage	1/61 (1.6%)	1
Respiratory distress	1/61 (1.6%)	1
Vascular disorders
Aortic thrombosis	1/61 (1.6%)	1
Orthostatic hypotension	1/61 (1.6%)	2
Superior vena cava syndrome	1/61 (1.6%)	1
Other (Not Including Serious) Adverse Events
	Gemcitabine + Cisplatin + Necitumumab
	Affected / at Risk (%)	# Events
Total	61/61 (100%)
Blood and lymphatic system disorders
Anaemia	15/61 (24.6%)	38
Iron deficiency anaemia	1/61 (1.6%)	1
Leukopenia	3/61 (4.9%)	6
Neutropenia	19/61 (31.1%)	51
Thrombocytopenia	10/61 (16.4%)	20
Cardiac disorders
Myocardial ischaemia	1/61 (1.6%)	1
Palpitations	1/61 (1.6%)	1
Sinus tachycardia	1/61 (1.6%)	1
Tachycardia	2/61 (3.3%)	2
Ear and labyrinth disorders
Deafness	1/61 (1.6%)	1
Hearing impaired	2/61 (3.3%)	2
Hypoacusis	1/61 (1.6%)	1
Ototoxicity	7/61 (11.5%)	14
Tinnitus	4/61 (6.6%)	4
Vertigo	1/61 (1.6%)	1
Eye disorders
Blepharitis	1/61 (1.6%)	1
Cataract	1/61 (1.6%)	1
Dry eye	3/61 (4.9%)	3
Growth of eyelashes	1/61 (1.6%)	1
Lacrimation increased	1/61 (1.6%)	1
Visual acuity reduced	2/61 (3.3%)	2
Gastrointestinal disorders
Abdominal distension	3/61 (4.9%)	3
Abdominal pain	8/61 (13.1%)	10
Abdominal pain upper	5/61 (8.2%)	5
Cheilitis	1/61 (1.6%)	2
Constipation	20/61 (32.8%)	25
Diarrhoea	18/61 (29.5%)	29
Dry mouth	1/61 (1.6%)	1
Dyspepsia	3/61 (4.9%)	6
Dysphagia	7/61 (11.5%)	7
Gastrointestinal pain	1/61 (1.6%)	1
Gastrooesophageal reflux disease	2/61 (3.3%)	2
Lip dry	1/61 (1.6%)	1
Lower gastrointestinal haemorrhage	1/61 (1.6%)	1
Mouth ulceration	2/61 (3.3%)	2
Nausea	45/61 (73.8%)	79
Odynophagia	2/61 (3.3%)	2
Oesophageal pain	1/61 (1.6%)	1
Oesophagitis	1/61 (1.6%)	1
Rectal haemorrhage	1/61 (1.6%)	1
Retching	1/61 (1.6%)	1
Stomatitis	21/61 (34.4%)	44
Vomiting	22/61 (36.1%)	39
General disorders
Asthenia	25/61 (41%)	83
Axillary pain	1/61 (1.6%)	1
Chest pain	1/61 (1.6%)	1
Chills	3/61 (4.9%)	3
Face oedema	2/61 (3.3%)	2
Fatigue	22/61 (36.1%)	39
Feeling cold	2/61 (3.3%)	2
Gait disturbance	3/61 (4.9%)	3
General physical health deterioration	1/61 (1.6%)	1
Influenza like illness	2/61 (3.3%)	2
Infusion site extravasation	1/61 (1.6%)	1
Infusion site pain	2/61 (3.3%)	2
Infusion site urticaria	1/61 (1.6%)	1
Malaise	5/61 (8.2%)	5
Mucosal dryness	2/61 (3.3%)	4
Mucosal inflammation	7/61 (11.5%)	9
Non-cardiac chest pain	4/61 (6.6%)	8
Oedema	1/61 (1.6%)	1
Oedema peripheral	6/61 (9.8%)	7
Pain	2/61 (3.3%)	2
Pyrexia	12/61 (19.7%)	17
Immune system disorders
Hypersensitivity	1/61 (1.6%)	1
Infections and infestations
Adenoviral conjunctivitis	1/61 (1.6%)	1
Bronchitis	1/61 (1.6%)	1
Candida infection	1/61 (1.6%)	1
Clostridium difficile infection	1/61 (1.6%)	2
Conjunctivitis	6/61 (9.8%)	11
Dermatophytosis of nail	1/61 (1.6%)	1
Device related infection	1/61 (1.6%)	1
Folliculitis	1/61 (1.6%)	1
Gastroenteritis	3/61 (4.9%)	3
Genital infection fungal	1/61 (1.6%)	1
Herpes virus infection	1/61 (1.6%)	1
Impetigo	1/61 (1.6%)	1
Influenza	1/61 (1.6%)	2
Nail infection	2/61 (3.3%)	4
Nasopharyngitis	2/61 (3.3%)	2
Oral candidiasis	1/61 (1.6%)	1
Paronychia	12/61 (19.7%)	40
Pharyngitis	2/61 (3.3%)	2
Pneumonia	1/61 (1.6%)	1
Respiratory tract infection	3/61 (4.9%)	3
Rhinitis	1/61 (1.6%)	1
Scrotal infection	1/49 (2%)	1
Skin infection	2/61 (3.3%)	3
Soft tissue infection	1/61 (1.6%)	1
Upper respiratory tract infection	1/61 (1.6%)	1
Urinary tract infection	6/61 (9.8%)	6
Viral infection	1/61 (1.6%)	1
Wound infection	1/61 (1.6%)	1
Injury, poisoning and procedural complications
Fall	2/61 (3.3%)	2
Fracture	1/61 (1.6%)	1
Infusion related reaction	2/61 (3.3%)	2
Investigations
Alanine aminotransferase increased	2/61 (3.3%)	2
Aspartate aminotransferase increased	1/61 (1.6%)	1
Blood alkaline phosphatase increased	1/61 (1.6%)	1
Blood bilirubin increased	1/61 (1.6%)	1
Blood creatinine increased	2/61 (3.3%)	2
Blood urea increased	1/61 (1.6%)	1
Fibrin d dimer increased	1/61 (1.6%)	1
Glomerular filtration rate increased	1/61 (1.6%)	1
Haemoglobin decreased	1/61 (1.6%)	1
Lymphocyte count decreased	1/61 (1.6%)	1
Lymphocyte count increased	1/61 (1.6%)	1
Neutrophil count decreased	5/61 (8.2%)	11
Platelet count decreased	5/61 (8.2%)	11
Platelet count increased	3/61 (4.9%)	3
Respiratory rate increased	1/61 (1.6%)	1
Troponin i increased	1/61 (1.6%)	1
Weight decreased	18/61 (29.5%)	24
Weight increased	5/61 (8.2%)	5
White blood cell count decreased	3/61 (4.9%)	3
Metabolism and nutrition disorders
Cachexia	1/61 (1.6%)	1
Decreased appetite	35/61 (57.4%)	52
Dehydration	5/61 (8.2%)	8
Hypercalcaemia	1/61 (1.6%)	1
Hyperglycaemia	2/61 (3.3%)	5
Hyperkalaemia	3/61 (4.9%)	4
Hypermagnesaemia	1/61 (1.6%)	1
Hypernatraemia	1/61 (1.6%)	1
Hypoalbuminaemia	2/61 (3.3%)	2
Hypocalcaemia	2/61 (3.3%)	11
Hypokalaemia	8/61 (13.1%)	19
Hypomagnesaemia	20/61 (32.8%)	45
Hyponatraemia	2/61 (3.3%)	3
Hypophosphataemia	1/61 (1.6%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	5/61 (8.2%)	6
Arthritis	1/61 (1.6%)	1
Back pain	4/61 (6.6%)	6
Flank pain	3/61 (4.9%)	3
Groin pain	1/61 (1.6%)	1
Muscle spasms	1/61 (1.6%)	1
Muscular weakness	5/61 (8.2%)	5
Musculoskeletal chest pain	3/61 (4.9%)	3
Musculoskeletal pain	3/61 (4.9%)	3
Myalgia	1/61 (1.6%)	1
Neck pain	1/61 (1.6%)	1
Pain in extremity	7/61 (11.5%)	7
Nervous system disorders
Aphasia	1/61 (1.6%)	1
Aphonia	1/61 (1.6%)	1
Ataxia	1/61 (1.6%)	1
Cerebrovascular accident	1/61 (1.6%)	1
Dizziness	14/61 (23%)	17
Dysaesthesia	1/61 (1.6%)	1
Dysarthria	1/61 (1.6%)	1
Dysgeusia	8/61 (13.1%)	8
Headache	10/61 (16.4%)	12
Ischaemic stroke	1/61 (1.6%)	1
Lethargy	2/61 (3.3%)	2
Neuralgia	1/61 (1.6%)	1
Neuropathy peripheral	4/61 (6.6%)	10
Neurotoxicity	4/61 (6.6%)	4
Paraesthesia	5/61 (8.2%)	8
Peripheral motor neuropathy	3/61 (4.9%)	4
Peripheral sensory neuropathy	1/61 (1.6%)	1
Syncope	3/61 (4.9%)	3
Tremor	1/61 (1.6%)	1
Psychiatric disorders
Anxiety	4/61 (6.6%)	4
Confusional state	2/61 (3.3%)	2
Delirium	1/61 (1.6%)	1
Depression	2/61 (3.3%)	2
Insomnia	12/61 (19.7%)	14
Irritability	1/61 (1.6%)	1
Renal and urinary disorders
Acute kidney injury	2/61 (3.3%)	2
Cystitis noninfective	1/61 (1.6%)	1
Dysuria	3/61 (4.9%)	3
Haematuria	2/61 (3.3%)	2
Micturition frequency decreased	1/61 (1.6%)	1
Proteinuria	3/61 (4.9%)	3
Urinary incontinence	1/61 (1.6%)	1
Urinary retention	2/61 (3.3%)	2
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/49 (2%)	1
Testicular pain	1/49 (2%)	1
Respiratory, thoracic and mediastinal disorders
Acute interstitial pneumonitis	1/61 (1.6%)	1
Atelectasis	1/61 (1.6%)	1
Bronchospasm	1/61 (1.6%)	1
Catarrh	3/61 (4.9%)	4
Chronic obstructive pulmonary disease	1/61 (1.6%)	1
Cough	17/61 (27.9%)	24
Dysphonia	2/61 (3.3%)	2
Dyspnoea	16/61 (26.2%)	23
Epistaxis	7/61 (11.5%)	8
Haemoptysis	6/61 (9.8%)	12
Hiccups	5/61 (8.2%)	5
Nasal congestion	1/61 (1.6%)	1
Nasal dryness	1/61 (1.6%)	1
Oropharyngeal discomfort	1/61 (1.6%)	1
Pleural effusion	1/61 (1.6%)	1
Pleuritic pain	1/61 (1.6%)	2
Productive cough	9/61 (14.8%)	14
Pulmonary embolism	3/61 (4.9%)	3
Rhinorrhoea	3/61 (4.9%)	3
Skin and subcutaneous tissue disorders
Acne	2/61 (3.3%)	2
Alopecia	9/61 (14.8%)	10
Decubitus ulcer	1/61 (1.6%)	1
Dermatitis	1/61 (1.6%)	1
Dermatitis acneiform	12/61 (19.7%)	17
Dry skin	12/61 (19.7%)	25
Erythema	1/61 (1.6%)	1
Hair colour changes	1/61 (1.6%)	1
Hair disorder	1/61 (1.6%)	1
Hirsutism	1/12 (8.3%)	1
Hypertrichosis	1/61 (1.6%)	1
Nail dystrophy	1/61 (1.6%)	1
Onycholysis	2/61 (3.3%)	2
Pain of skin	1/61 (1.6%)	1
Palmar-plantar erythrodysaesthesia syndrome	1/61 (1.6%)	2
Penile ulceration	1/49 (2%)	1
Pruritus	5/61 (8.2%)	6
Rash	28/61 (45.9%)	109
Rash generalised	1/61 (1.6%)	1
Rash maculo-papular	4/61 (6.6%)	5
Rash vesicular	1/61 (1.6%)	1
Scab	1/61 (1.6%)	1
Skin fissures	8/61 (13.1%)	15
Skin toxicity	1/61 (1.6%)	1
Skin ulcer	1/61 (1.6%)	2
Urticaria	1/61 (1.6%)	11
Xeroderma	1/61 (1.6%)	1
Vascular disorders
Aortic thrombosis	1/61 (1.6%)	1
Embolism	2/61 (3.3%)	2
Haematoma	1/61 (1.6%)	1
Hypertension	5/61 (8.2%)	5
Hypotension	3/61 (4.9%)	3
Jugular vein distension	1/61 (1.6%)	1
Jugular vein thrombosis	2/61 (3.3%)	2
Orthostatic hypotension	2/61 (3.3%)	2
Peripheral artery thrombosis	1/61 (1.6%)	1
Peripheral venous disease	1/61 (1.6%)	1
Raynaud's phenomenon	1/61 (1.6%)	1
Superior vena cava syndrome	2/61 (3.3%)	2

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.