A Study of Tarceva (Erlotinib) Monotherapy in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01996332
• Collaborator: (none)
• Enrollment: 1,805
• Locations: 94
• Arm: 1
• Duration (Months): 102
• Patients Per Site: 19.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy and safety of oral Tarceva in patients with advanced NSCLC for whom Tarceva monotherapy is considered the best therapeutic option. The anticipated time on study treatment is 3-12 months.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer	Drug: erlotinib [Tarceva]	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 1805 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Study of the Effect of Tarceva Monotherapy on Treatment Response in Patients With Advanced Non-small Cell Lung Cancer for Whom Tarceva Monotherapy is Considered the Best Option
• Study Start Date: Apr 1, 2004
• Actual Primary Completion Date: Oct 1, 2012
• Actual Study Completion Date: Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tarceva Arm	Drug: erlotinib [Tarceva]; 150 mg/day until progressive disease or unacceptable toxicity

Outcome Measures

Primary Outcome Measures

1. Time to Disease Progression or Death by Line of Treatment [Baseline, every 6-8 weeks up to 3 years until disease progression or death]

   Time to progression or death was defined as the time from inclusion to the date of disease progression or death, whichever occurred first.

Secondary Outcome Measures

1. Percentage of Participants Achieving Clinical Benefit by Line of Treatment [Baseline, every 6-8 weeks up to 3 years or until death]

   Efficacy was analyzed in terms of clinical benefit, defined as the sum of the number of participants achieving complete response [CR], partial response [PR], or stable disease [SD]. Tumor response was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.0. CR was defined as disappearance of all target and non-target lesions. PR was defined as greater than or equal to (≥)30 percent (%) decrease in sum of longest diameters of target lesions taking as reference baseline sum longest diameters associated to non-progressive disease response for non target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference smallest sum of longest dimensions since treatment started associated to non-progressive disease response for non target lesions.

2. Overall Survival (OS) by Line of Treatment [Baseline, every 6-8 weeks up to 3 years, or until death]

   Time in months from the start of study treatment to date of death due to any cause. OS was calculated as (the death date or last known alive date [if death date was unavailable] minus the date of first dose of study medication plus 1 divided by 30.44).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• adult patients >=18 years of age;

• locally advanced or metastatic NSCLC (Stage IIIB or IV);

• not a candidate for curative surgery or radical chemotherapy;

• no brain metastases, or clinically stable metastases for >=2 months.

Exclusion Criteria:

• radiotherapy over the previous 2 weeks;

• weight loss >10% in the previous 6 weeks.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Alcoy	Alicante	Spain	03804
2		Elche	Alicante	Spain	03203
3		Almería	Almeria	Spain	04009
4		Don Benito	Badajoz	Spain	06400
5		Merida	Badajoz	Spain	06800
6		Badalona	Barcelona	Spain	08911
7		Granollers	Barcelona	Spain	08400
8		Manresa	Barcelona	Spain	08243
9		Mataro	Barcelona	Spain	08304
10		Sabadell, Barcelona	Barcelona	Spain	08208
11		Sant Coloma Gramenet	Barcelona	Spain	08923
12		Sant Pere de Ribes	Barcelona	Spain	08810
13		Terrassa	Barcelona	Spain	08221
14		VIC	Barcelona	Spain	08500
15		Algeciras	Cadiz	Spain	11207
16		Cádiz	Cadiz	Spain	11009
17		Jerez de La Frontera	Cadiz	Spain	11407
18		Puerto Real	Cadiz	Spain	11510
19		Santander	Cantabria	Spain	39008
20		Torrevieja	Cantabria	Spain	03180
21		Baza	Granada	Spain	18800
22		San Sebastian	Guipuzcoa	Spain	20014
23		Ibiza	Islas Baleares	Spain	07800
24		Palma de Mallorca	Islas Baleares	Spain	07012
25		Palma De Mallorca	Islas Baleares	Spain	07014
26		Palma de Mallorca	Islas Baleares	Spain	07198
27		Ferrol	La Coruña	Spain	15405
28		La Coruna	La Coruña	Spain	15009
29		Las Palmas de Gran Canaria	Las Palmas	Spain	35016
30		Las Palmas de Gran Canaria	Las Palmas	Spain	35020
31		Alcorcon	Madrid	Spain	28922
32		Cartagena	Murcia	Spain	30203
33		Pamplona	Navarra	Spain	31008
34		Vigo	Pontevedra	Spain	36204
35		Vigo	Pontevedra	Spain	36211
36		La Laguna	Tenerife	Spain	38320
37		Santa Cruz de Tenerife	Tenerife	Spain	38010
38		Sagunto	Valencia	Spain	46520
39		Barakaldo	Vizcaya	Spain	48903
40		Bilbao	Vizcaya	Spain	48013
41		Alicante		Spain	3010
42		Avila		Spain	05071
43		Badajoz		Spain	06080
44		Barcelona		Spain	08003
45		Barcelona		Spain	08017
46		Barcelona		Spain	08022
47		Barcelona		Spain	08029
48		Barcelona		Spain	08036
49		Barcelona		Spain	08041
50		Barcelona		Spain	08227
51		Barcelona		Spain	08907
52		Barcelona		Spain	08916
53		Burgos		Spain	09006
54		Caceres		Spain	10003
55		Castellon		Spain	12002
56		Cordoba		Spain	14004
57		Girona		Spain	17007
58		Granada		Spain	18003
59		Granada		Spain	18014
60		Huelva		Spain	21005
61		Jaen		Spain	23007
62		La Coruña		Spain	15006
63		Leon		Spain	24071
64		Lerida		Spain	25198
65		Lugo		Spain	27004
66		Madrid		Spain	28002
67		Madrid		Spain	28006
68		Madrid		Spain	28033
69		Madrid		Spain	28034
70		Madrid		Spain	28040
71		Madrid		Spain	28041
72		Madrid		Spain	28046
73		Madrid		Spain	28222
74		Madrid		Spain	28660
75		Madrid		Spain	28935
76		Malaga		Spain	29010
77		Murcia		Spain	30008
78		Murcia		Spain	30120
79		Navarra		Spain	31008
80		Orense		Spain	32005
81		Palencia		Spain	34005
82		Salamanca		Spain	37007
83		Segovia		Spain	40002
84		Sevilla		Spain	41009
85		Sevilla		Spain	41013
86		Sevilla		Spain	41014
87		Valencia		Spain	41014
88		Valencia		Spain	46009
89		Valencia		Spain	46010
90		Valencia		Spain	46015
91		Valencia		Spain	46017
92		Valencia		Spain	46026
93		Valladolid		Spain	47010
94		Zaragoza		Spain	50009

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Chair: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01996332
• Other Study ID Numbers: ML17915
• First Posted: Nov 27, 2013
• Last Update Posted: Jul 10, 2014
• Last Verified: Jun 1, 2014

• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Erlotinib Hydrochloride

Study Results

Participant Flow

Pre-assignment Detail	Three cohorts were established in participants with advanced non-small cell lung cancer (NSCLC) based on previous chemotherapy treatment received: first line of treatment (where conventional chemotherapy is not indicated), second line of treatment, and third and subsequent lines of treatment. Inclusion was competitive.

Arm/Group Title	Erlotinib 150 Milligrams Per Day (mg/Day)
Arm/Group Description	Participants received erlotinib 150 milligrams/day (mg/day), orally, until progressive disease or unacceptable toxicity.
Period Title: Overall Study
STARTED	1805
COMPLETED	0
NOT COMPLETED	1805

Baseline Characteristics

Arm/Group Title	Erlotinib 150 mg/Day
Arm/Group Description	Participants received erlotinib 150 mg/day, orally, until progressive disease or unacceptable toxicity.
Overall Participants	1805
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.55 (11.75)
Sex: Female, Male (Count of Participants)
Female	520 28.8%
Male	1285 71.2%

Outcome Measures

1. Primary Outcome

Title	Time to Disease Progression or Death by Line of Treatment
Description	Time to progression or death was defined as the time from inclusion to the date of disease progression or death, whichever occurred first.
Time Frame	Baseline, every 6-8 weeks up to 3 years until disease progression or death

Outcome Measure Data

Analysis Population Description

ITT Population; data were analyzed in 6 cohorts, with erlotinib treatment as: 1) first line; 2) maintenance after first line; 3) second line; 4) maintenance after second line; 5) third or subsequent line; or 6) maintenance after third line

Arm/Group Title	Erlotinib 150 mg/Day
Arm/Group Description	Participants received erlotinib 150 mg/day, orally, until progressive disease or unacceptable toxicity.
Measure Participants	1805
1st Line	3.4
Maintenance after 1st Line	4.7
2nd Line	2.7
Maintenance after 2nd Line	3.9
3rd or Subsequent Line	2.4
Maintenance after 3rd Line	2.8

2. Secondary Outcome

Title	Percentage of Participants Achieving Clinical Benefit by Line of Treatment
Description	Efficacy was analyzed in terms of clinical benefit, defined as the sum of the number of participants achieving complete response [CR], partial response [PR], or stable disease [SD]. Tumor response was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.0. CR was defined as disappearance of all target and non-target lesions. PR was defined as greater than or equal to (≥)30 percent (%) decrease in sum of longest diameters of target lesions taking as reference baseline sum longest diameters associated to non-progressive disease response for non target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference smallest sum of longest dimensions since treatment started associated to non-progressive disease response for non target lesions.
Time Frame	Baseline, every 6-8 weeks up to 3 years or until death

Outcome Measure Data

Analysis Population Description

Response evaluable population: participants with measurable disease and with matching criteria to have a response assessment; data were analyzed in 6 cohorts, with erlotinib treatment as: 1) first line; 2) maintenance after first line; 3) second line; 4) maintenance after second line; 5) third or subsequent line; or 6) maintenance after third line

Arm/Group Title	Erlotinib 150 mg/Day
Arm/Group Description	Participants received erlotinib 150 mg/day, orally, until progressive disease or unacceptable toxicity.
Measure Participants	1261
1st line	70.32 3.9%
Maintenance treatment after 1st line	70.00 3.9%
2nd line	58.04 3.2%
Maintenance treatment after 2nd line	73.68 4.1%
3rd or subsequent line	52.71 2.9%
Maintenance treatment after 3rd line	50.00 2.8%

3. Secondary Outcome

Title	Overall Survival (OS) by Line of Treatment
Description	Time in months from the start of study treatment to date of death due to any cause. OS was calculated as (the death date or last known alive date [if death date was unavailable] minus the date of first dose of study medication plus 1 divided by 30.44).
Time Frame	Baseline, every 6-8 weeks up to 3 years, or until death

Outcome Measure Data

Analysis Population Description

ITT Population; data were analyzed in 6 cohorts, with erlotinib treatment as: 1) first line; 2) maintenance after first line; 3) second line; 4) maintenance after second line; 5) third or subsequent line; or 6) maintenance after third line

Arm/Group Title	Erlotinib 150 mg/Day
Arm/Group Description	Participants received erlotinib 150 mg/day, orally, until progressive disease or unacceptable toxicity.
Measure Participants	1805
1st Line	6.4
Sequential treatment after 1st line	12.1
2nd Line	5.9
Sequential treatment after 2nd line	7.1
3rd Line or subsequent	5.2
Sequential treatment after 3rd line	3.9

Adverse Events

Time Frame	From the administration of first dose of study medication to the end of study or until death.
Adverse Event Reporting Description	Nonserious adverse events presented in this record include all adverse events reported during the study, not just nonserious events.
Arm/Group Title	Erlotinib 150 mg/Day
Arm/Group Description	Participants received erlotinib 150 mg/day, orally, until progressive disease or unacceptable toxicity.
All Cause Mortality
	Erlotinib 150 mg/Day
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Erlotinib 150 mg/Day
	Affected / at Risk (%)	# Events
Total	566/1805 (31.4%)
Blood and lymphatic system disorders
Hemoglobbin	3/1805 (0.2%)
Hemorrhage	17/1805 (0.9%)
Cardiac disorders
Cardiac arrhythmia	4/1805 (0.2%)
Cardiac ischemia	6/1805 (0.3%)
Cardiopulmonary arrest	6/1805 (0.3%)
Left ventricular systolic dysfunction	4/1805 (0.2%)
Pericardial effusion	7/1805 (0.4%)
Pericarditis	1/1805 (0.1%)
Right ventricular dysfunction	1/1805 (0.1%)
Eye disorders
Diplopia	1/1805 (0.1%)
Keratitis	1/1805 (0.1%)
Gastrointestinal disorders
Constipation	1/1805 (0.1%)
Diarrhea	28/1805 (1.6%)
Dyspepsia/heartburn	1/1805 (0.1%)
Dysphagia	6/1805 (0.3%)
Esophagitis	1/1805 (0.1%)
Gastrointestinal/other	1/1805 (0.1%)
Ileus GI	4/1805 (0.2%)
Intestinal perforation	2/1805 (0.1%)
Mucositis	5/1805 (0.3%)
Nausea	6/1805 (0.3%)
Obstruction/GU	1/1805 (0.1%)
Vomiting	7/1805 (0.4%)
Ascites	2/1805 (0.1%)
Pain - abdominal NOS	7/1805 (0.4%)
Pain - liver	1/1805 (0.1%)
Obstruction/GI	4/1805 (0.2%)
General disorders
Asthenia	17/1805 (0.9%)
Constitutional symptoms/other	14/1805 (0.8%)
Fever	17/1805 (0.9%)
Edema Limb	2/1805 (0.1%)
Pain NOS	22/1805 (1.2%)
Flu-like syndrome	1/1805 (0.1%)
Ill-defined disorder	1/1805 (0.1%)
Uncoded	2/1805 (0.1%)
Hepatobiliary disorders
Hepatic cyst	1/1805 (0.1%)
Liver dysfunction	4/1805 (0.2%)
Immune system disorders
Antiphospholipid syndrome	1/1805 (0.1%)
Infections and infestations
Febrile neutropenia	2/1805 (0.1%)
Gallbladder infection	1/1805 (0.1%)
Infection NOS	67/1805 (3.7%)
Infection - anal/perianal	1/1805 (0.1%)
Infection - appendix	1/1805 (0.1%)
Infection - blood	6/1805 (0.3%)
Infection - brain (encephalitis, infectious)	1/1805 (0.1%)
Infection - bronchus	5/1805 (0.3%)
Infection - catheter - related	1/1805 (0.1%)
Infection - kidney	1/1805 (0.1%)
Infection - liver	1/1805 (0.1%)
Infection - lung (pneumonia)	44/1805 (2.4%)
Infection - skin (cellulitis)	2/1805 (0.1%)
Infection - soft tissue NOS	3/1805 (0.2%)
Infection - upper aerodigestive NOS	1/1805 (0.1%)
Infection - urinary tract NOS	6/1805 (0.3%)
Infection - wound	1/1805 (0.1%)
Injury, poisoning and procedural complications
Alcohol Poisoning	1/1805 (0.1%)
Fracture	4/1805 (0.2%)
Syndromes/other-superior cava vein	9/1805 (0.5%)
Investigations
Neutrophils	2/1805 (0.1%)
Platelets	1/1805 (0.1%)
Weight loss	1/1805 (0.1%)
Bilirubin	2/1805 (0.1%)
Metabolism and nutrition disorders
Anorexia	6/1805 (0.3%)
Acidosis	1/1805 (0.1%)
Hypercalcemia	4/1805 (0.2%)
Hyperglycemia	3/1805 (0.2%)
Hyponatremia	1/1805 (0.1%)
Musculoskeletal and connective tissue disorders
Muscle weakness	1/1805 (0.1%)
Musculoskeletal/other	1/1805 (0.1%)
Trismus	1/1805 (0.1%)
Pain - bone	3/1805 (0.2%)
Pain - chest wall	7/1805 (0.4%)
Pain - joint	1/1805 (0.1%)
Pain - limb	3/1805 (0.2%)
Pain - muscle	15/1805 (0.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary Malignancy	1/1805 (0.1%)
Nervous system disorders
Ataxia	2/1805 (0.1%)
CNS ischemia	14/1805 (0.8%)
Cognitive disturbance	2/1805 (0.1%)
Dizziness	3/1805 (0.2%)
Encephalopathy	1/1805 (0.1%)
Involuntary movement	1/1805 (0.1%)
Neuropathy/motor	7/1805 (0.4%)
Neuropathy/sensory	2/1805 (0.1%)
Seizures	2/1805 (0.1%)
Somnolence	2/1805 (0.1%)
Speech impairment	2/1805 (0.1%)
Syncope	4/1805 (0.2%)
Pain - headache	5/1805 (0.3%)
Pain - neuralgia/peripheral nerve	1/1805 (0.1%)
Psychiatric disorders
Confusion	11/1805 (0.6%)
Mood alteration - agitation	2/1805 (0.1%)
Mood alteration - anxiety	2/1805 (0.1%)
Neurology/other	15/1805 (0.8%)
Psychosis	1/1805 (0.1%)
Renal and urinary disorders
Renal failure	10/1805 (0.6%)
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage	21/1805 (1.2%)
Pain - pleura	1/1805 (0.1%)
Adult respiratory distress syndrome	3/1805 (0.2%)
Airway obstruction/upper respiratory	1/1805 (0.1%)
Bronchospasm	3/1805 (0.2%)
Cough	4/1805 (0.2%)
Dyspnea	188/1805 (10.4%)
Hypoxia	2/1805 (0.1%)
Pleural effusion	9/1805 (0.5%)
Pneumonitis	3/1805 (0.2%)
Pneumothorax	4/1805 (0.2%)
Pulmonary/obstruction/stenosis of airway (bronchus)	1/1805 (0.1%)
Pulmonary/others	6/1805 (0.3%)
Tracheal fistula	1/1805 (0.1%)
Skin and subcutaneous tissue disorders
Sweating	1/1805 (0.1%)
Dermatology/skin - other	4/1805 (0.2%)
Rash	5/1805 (0.3%)
Social circumstances
Drug abuser	1/1805 (0.1%)
Opioid abuse	2/1805 (0.1%)
Surgical and medical procedures
Intraoperative complications	1/1805 (0.1%)
Vascular disorders
Hypotension	1/1805 (0.1%)
Phlebitis	2/1805 (0.1%)
Thrombosis/embolism	25/1805 (1.4%)
Vascular/other	2/1805 (0.1%)
Other (Not Including Serious) Adverse Events
	Erlotinib 150 mg/Day
	Affected / at Risk (%)	# Events
Total	1695/1797 (94.3%)
Blood and lymphatic system disorders
Hemoglobin	89/1797 (5%)
Febrile neutropenia	2/1797 (0.1%)
Cardiac disorders
Cardiac arrhythmia	27/1797 (1.5%)
Palpitations	1/1797 (0.1%)
Pericardial effusion	8/1797 (0.4%)
Cardiac ischemia	7/1797 (0.4%)
Cardiopulmonary arrest	6/1797 (0.3%)
Left ventricular systolic dysfunction	5/1797 (0.3%)
Right ventricular dysfunction	2/1797 (0.1%)
Valvular heart disease	2/1797 (0.1%)
Pericarditis	1/1797 (0.1%)
Ear and labyrinth disorders
Hearing	5/1797 (0.3%)
Tinnitus	3/1797 (0.2%)
Pain - ear	1/1797 (0.1%)
Endocrine disorders
Cushingoid	6/1797 (0.3%)
Eye disorders
Blurred vision	3/1797 (0.2%)
Eye disorder	48/1797 (2.7%)
Watery eye	7/1797 (0.4%)
Dry eye	6/1797 (0.3%)
Diplopia	5/1797 (0.3%)
Keratitis	3/1797 (0.2%)
Cataract	2/1797 (0.1%)
Vision-flashing lights/floaters	1/1797 (0.1%)
Pain - eye	5/1797 (0.3%)
Gastrointestinal disorders
Mucosal dryness	6/1797 (0.3%)
Diarrhea	631/1797 (35.1%)
Vomiting	204/1797 (11.4%)
Nausea	196/1797 (10.9%)
Mucositis	167/1797 (9.3%)
Constipation	110/1797 (6.1%)
Dysphagia	49/1797 (2.7%)
Dyspepsia/heartburn	40/1797 (2.2%)
Xerostomia	36/1797 (2%)
Gastrointestinal/other	35/1797 (1.9%)
Hemorrhoids	8/1797 (0.4%)
Incontinence, anal	7/1797 (0.4%)
Distension	6/1797 (0.3%)
Flatulence	5/1797 (0.3%)
Ileus GI	5/1797 (0.3%)
Esophagitis	4/1797 (0.2%)
Enteritis	2/1797 (0.1%)
Intestinal perforation	2/1797 (0.1%)
Anal fistula	1/1797 (0.1%)
Obstruction/GU	1/1797 (0.1%)
Tooth disorder	1/1797 (0.1%)
Hemorrhage/GI	43/1797 (2.4%)
Ascites	10/1797 (0.6%)
Pain - abdomen nos	108/1797 (6%)
Pain - dental/teeth/peridontal	1/1797 (0.1%)
Pain - rectum	1/1797 (0.1%)
Obstruction/GI	4/1797 (0.2%)
General disorders
Asthenia	650/1797 (36.2%)
Fever	210/1797 (11.7%)
Constitutional symptoms/other	42/1797 (2.3%)
Inflammation	5/1797 (0.3%)
Rigors/chills	3/1797 (0.2%)
Hypothermia	1/1797 (0.1%)
Hemorrhage/other	3/1797 (0.2%)
Edema limb	80/1797 (4.5%)
Edema	33/1797 (1.8%)
Edema head and neck	12/1797 (0.7%)
Lymphatic/other	2/1797 (0.1%)
Gait	8/1797 (0.4%)
Pain nos	229/1797 (12.7%)
Pain - face	2/1797 (0.1%)
Flu-like syndrome	102/1797 (5.7%)
Syndromes/other	3/1797 (0.2%)
Ill-defined disorder	1/1797 (0.1%)
Uncoded	11/1797 (0.6%)
Hepatobiliary disorders
Liver dysfunction	10/1797 (0.6%)
Hepatobiliary/other	6/1797 (0.3%)
Cholecystitis	1/1797 (0.1%)
Hepatic cysts	1/1797 (0.1%)
Pain - liver	8/1797 (0.4%)
Immune system disorders
Allergic reaction	3/1797 (0.2%)
Antiphospholipid syndrome	1/1797 (0.1%)
Infections and infestations
Rhinitis	14/1797 (0.8%)
Infection NOS	148/1797 (8.2%)
Infection - conjunctiva	108/1797 (6%)
Infection - lung (pneumonia)	51/1797 (2.8%)
Infection - ungual (nail)	51/1797 (2.8%)
Infection - urinary tract nos	31/1797 (1.7%)
Infection - skin (cellulitis)	29/1797 (1.6%)
Infection - bronchus	18/1797 (1%)
Infection - eye nos	17/1797 (0.9%)
Infection - soft tissue nos	13/1797 (0.7%)
Infection - upper aerodigestive nos	13/1797 (0.7%)
Infection - pharynx	9/1797 (0.5%)
Infection - blood	8/1797 (0.4%)
Infection - lip/perioral	7/1797 (0.4%)
Infection - anal/perianal	5/1797 (0.3%)
Infection - upper airway nos	4/1797 (0.2%)
Tooth infection	4/1797 (0.2%)
Infection - vagina	3/1797 (0.2%)
Infection - auditory ear	3/1797 (0.2%)
Gallbladder infection	2/1797 (0.1%)
Infection - brain (encephalitis, infectious)	2/1797 (0.1%)
Infection - sinus	2/1797 (0.1%)
Infection - bone (osteomyelitis)	1/1797 (0.1%)
Infection - kidney	1/1797 (0.1%)
Infection - liver	1/1797 (0.1%)
Infection - salivary gland	1/1797 (0.1%)
Infection - dental-tooth	1/1797 (0.1%)
Infection - peritoneal cavity	1/1797 (0.1%)
Infection - wound	1/1797 (0.1%)
Infection - appendix	1/1797 (0.1%)
Infection - catheter-related	1/1797 (0.1%)
Infection - colon	1/1797 (0.1%)
Infection - vulva	1/1797 (0.1%)
Injury, poisoning and procedural complications
Alcohol poisoning	1/1797 (0.1%)
Burn	1/1797 (0.1%)
Fracture	12/1797 (0.7%)
Syndromes/other-superior cava vein	15/1797 (0.8%)
Thrombosis/embolism	42/1797 (2.3%)
Investigations
Platelets	8/1797 (0.4%)
Neutrophils	7/1797 (0.4%)
Leucocytes	4/1797 (0.2%)
Lymphopenia	1/1797 (0.1%)
Band neutrophil percentage increased	1/1797 (0.1%)
Weight loss	91/1797 (5.1%)
Weight gain	1/1797 (0.1%)
ADH	1/1797 (0.1%)
Bilirubin	23/1797 (1.3%)
ALT	14/1797 (0.8%)
AST	14/1797 (0.8%)
Alkaline phosphatase	11/1797 (0.6%)
GGT	10/1797 (0.6%)
Hypercholesterolemia	4/1797 (0.2%)
Amylase	1/1797 (0.1%)
CPK	1/1797 (0.1%)
Metabolism and nutrition disorders
Glucose intolerance	1/1797 (0.1%)
Anorexia	462/1797 (25.7%)
Dehydration	4/1797 (0.2%)
Hyperglycemia	17/1797 (0.9%)
Hypercalcemia	11/1797 (0.6%)
Hyperkalemia	9/1797 (0.5%)
Hypocalcemia	8/1797 (0.4%)
Hyponatremia	7/1797 (0.4%)
Metabolic lab/other	6/1797 (0.3%)
Hyperuricemia	5/1797 (0.3%)
Hypoalbuminemia	4/1797 (0.2%)
Hypokalemia	3/1797 (0.2%)
Hypoglycemia	2/1797 (0.1%)
Acidosis	1/1797 (0.1%)
Hypernatremia	1/1797 (0.1%)
Hypomagnesemia	1/1797 (0.1%)
Hypophosphatemia	1/1797 (0.1%)
Alkalosis	1/1797 (0.1%)
Hypertriglyceridemia	1/1797 (0.1%)
Musculoskeletal and connective tissue disorders
Musculoskeletal/other	77/1797 (4.3%)
Muscle weakness	24/1797 (1.3%)
Arthritis	6/1797 (0.3%)
Osteonecrosis	1/1797 (0.1%)
Myositis	1/1797 (0.1%)
Trismus	1/1797 (0.1%)
Pain - chest wall	211/1797 (11.7%)
Pain - muscle	139/1797 (7.7%)
Pain - joint	95/1797 (5.3%)
Pain - bone	78/1797 (4.3%)
Pain - limb	51/1797 (2.8%)
Pain - neck	21/1797 (1.2%)
Pain - foot	2/1797 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pain - tumor	3/1797 (0.2%)
Secondary malignancy	1/1797 (0.1%)
Nervous system disorders
Vasovagal episodes	3/1797 (0.2%)
Dysgeusia	17/1797 (0.9%)
Taste Alteration (dysgeusia)	1/1797 (0.1%)
Dizziness	94/1797 (5.2%)
Neuropathy/sensory	74/1797 (4.1%)
Ataxia	57/1797 (3.2%)
Neurology/other	53/1797 (2.9%)
Neuropathy/motor	38/1797 (2.1%)
Somnolence	38/1797 (2.1%)
Cognitive disturbance	28/1797 (1.6%)
Speech impairment	27/1797 (1.5%)
CNS ischemia	16/1797 (0.9%)
Tremor	16/1797 (0.9%)
Syncope	15/1797 (0.8%)
Seizures	15/1797 (0.8%)
Memory impairment	11/1797 (0.6%)
Involuntary movement	6/1797 (0.3%)
Encephalopathy	5/1797 (0.3%)
Neuropathy cranial	5/1797 (0.3%)
Extrapyramidal disorder	1/1797 (0.1%)
Seizure	1/1797 (0.1%)
Pain - headache	97/1797 (5.4%)
Pain - neuralgia/peripheral nerve	18/1797 (1%)
Psychiatric disorders
Insomnia	67/1797 (3.7%)
Confusion	55/1797 (3.1%)
Mood alteration-anxiety	51/1797 (2.8%)
Mood alteration-depression	45/1797 (2.5%)
Mood alteration-agitation	23/1797 (1.3%)
Mood alteration	14/1797 (0.8%)
Psychosis	7/1797 (0.4%)
Mood alteration-depression-anxiety	4/1797 (0.2%)
Renal and urinary disorders
Hemorrhage/GU	14/1797 (0.8%)
Pain - Kidney	2/1797 (0.1%)
Renal failure	39/1797 (2.2%)
Cystitis	12/1797 (0.7%)
Urinary frequency	11/1797 (0.6%)
Renal/other	8/1797 (0.4%)
Incontinence, urinary	2/1797 (0.1%)
Urine colour change	2/1797 (0.1%)
Urinary retention	1/1797 (0.1%)
Urogenital disorder	1/1797 (0.1%)
Reproductive system and breast disorders
Sexual/reproductive function	3/1797 (0.2%)
Irregular menstruation	2/1797 (0.1%)
Vaginal dryness	1/1797 (0.1%)
Erectile dysfunction	1/1797 (0.1%)
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension	1/1797 (0.1%)
Bronchopulmonary hemorrhage	167/1797 (9.3%)
Pain - pleura	25/1797 (1.4%)
Pain - throat/pharynx/larynx	5/1797 (0.3%)
Dyspnea	691/1797 (38.5%)
Cough	436/1797 (24.3%)
Pulmonary/other	138/1797 (7.7%)
Voice changes	87/1797 (4.8%)
Bronchospasm	18/1797 (1%)
Pleural effusion	12/1797 (0.7%)
Hypoxia	8/1797 (0.4%)
Hiccoughs	7/1797 (0.4%)
Pulmonary/obstruction/stenosis of airway (bronchus)	6/1797 (0.3%)
Pneumonitis	4/1797 (0.2%)
Pneumothorax	4/1797 (0.2%)
Atelectasis	3/1797 (0.2%)
Adult respiratory distress syndrome	3/1797 (0.2%)
Chest tube drainage or leak	1/1797 (0.1%)
Trachael fistula	1/1797 (0.1%)
Airway obstruction/upper respiratory	1/1797 (0.1%)
Skin and subcutaneous tissue disorders
Sweating	10/1797 (0.6%)
Rash	897/1797 (49.9%)
Dermatology/skin-other	307/1797 (17.1%)
Acne	152/1797 (8.5%)
Dry skin	137/1797 (7.6%)
Pruritus	95/1797 (5.3%)
Alopecia	92/1797 (5.1%)
Nail changes	71/1797 (4%)
Ulceration	15/1797 (0.8%)
Hand foot skin reaction	9/1797 (0.5%)
Decubitus ulcer	6/1797 (0.3%)
Hyperpigmentation	4/1797 (0.2%)
Telangiectasia	1/1797 (0.1%)
Petechiae	6/1797 (0.3%)
Pain - scalp	1/1797 (0.1%)
Social circumstances
Opioid abuse	3/1797 (0.2%)
Drug abuser	1/1797 (0.1%)
Surgical and medical procedures
Intraoperative complications	1/1797 (0.1%)
Vascular disorders
Vasculitis	3/1797 (0.2%)
Hypotension	7/1797 (0.4%)
Hypertension	5/1797 (0.3%)
Pallor	6/1797 (0.3%)
Flushing	3/1797 (0.2%)
Vascular/other	10/1797 (0.6%)
Phlebitis	7/1797 (0.4%)

Limitations/Caveats

Nonserious adverse events presented in this record include all adverse events reported during the study, not just nonserious events.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The study being conducted under this agreement is part of the overall study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study, but after the first publication or presentation that involves the overall study. Sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.