Efficacy Trial Comparing ZD6474 With Erlotinib in NSCLC After Failure of at Least One Prior Chemotherapy

• Sponsor: Genzyme, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00364351
• Collaborator: (none)
• Enrollment: 1,574
• Locations: 153
• Arms: 2
• Duration (Months): 123
• Patients Per Site: 10.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To determine if ZD6474 a new investigational drug, is effective in treating Non Small Lung Cancer and if so, how it compares with another type of anti cancer therapy chemotherapy, Erlotinib

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer	Drug: Vandetanib; Drug: Erlotinib	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1574 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III, International, Randomised, Double Blind, Parallel-Group Study to Assess the Efficacy of Zactima™ Versus Tarceva® in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Failure of at Least One Prior Chemotherapy
• Study Start Date: Aug 1, 2006
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Nov 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Erlotinib	Drug: Erlotinib; oral dose; Other Names: Tarceva®
Experimental: 2 Vandetanib	Drug: Vandetanib; once daily oral tablet; Other Names: ZD6474 ZACTIMA™

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) [progressionRECIST tumour assessments carried out every 4 weeks up to week 16 then every 8 weeks thereafter from randomisation until the date of first documented objective disease progression or date of death from any cause, whichever came first, assessed.]

   Median time (in weeks) from randomisation until objective disease progression or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable Response Evaluation Criteria In Solid Tumors (RECIST) assessment. Progression was derived according to RECIST 1.0 and is defined as an increase of at least 20% in the total tumour size of measurable lesions over the nadir measurement, unequivocal progression in the non-target lesions or the appearance of one or more new lesions.

Secondary Outcome Measures

1. Overall Survival (OS) [Time to death in months]

   Overall survival is defined as the time from date of randomization until death. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive (ie their status must be known at the censored date and should not be lost to follow up or unknown).

2. Objective Response Rate (ORR) [RECIST tumour assessments every 4 weeks up to week 16 then every 8 weeks thereafter from randomisation until the date of first documented objective disease progression or date of death from any cause, whichever came first, assessed up to 21 months]

   The ORR is the number of patients that are responders ie those patients with a confirmed best objective response of complete response (CR) or partial response (PR) as determined according to RECIST 1.0. CR is defined as the disappearance of all target lesions with no evidence of tumour elsewhere and PR is defined as at least a 30% reduction in the total tumour size of measurable lesions with no new lesions and no progression in the non-target lesions.

3. Disease Control Rate (DCR) [RECIST tumour assessments carried out every 4 weeks until week 16 then every 8 weeks thereafter (+/- 3 days) from randomisation until objective progression]

   Disease control rate is defined as the number of patients who achieved disease control at least 8 weeks following randomisation. Disease control is defined as a best objective response of complete response (CR), partial response (PR) or stable disease (SD) >= 8 weeks as determined according to RECIST 1.0. CR is defined as the disappearance of all target lesions with no evidence of tumour elsewhere, PR is defined as at least a 30% reduction in the total tumour size of measurable lesions with no new lesions and no progression in the non-target lesions and SD >= 8 is assigned to patients who have not responded and have no evidence of progression at least 8 weeks after randomisation.

4. Time to Deterioration of Disease-related Symptoms (TDS) by EORTC Quality of Life Questionnaire - Pain [Disease-related symptom assessments are to be administered at screening (within 7 days before the first dose of study medication), every 4 weeks thereafter, at discontinuation of study treatment and at the 30-day follow-up visit]

   Pain was assessed as the average score of two items: Question 9 ("Have you had pain") and 19 ("Did pain interfere with your daily activities") of the QLQ-C30. Time to deterioration in symptoms is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 28 days. A patient is defined as having a deterioration in symptoms if they have a single visit assessment of 'worsened' with no visit assessment of 'improved' within the next 28 days.

5. Time to Deterioration of Disease-related Symptoms (TDS) by EORTC Quality of Life Questionnaire - Dyspnoea [Disease-related symptom assessments are to be administered at screening (within 7 days before the first dose of study medication), every 4 weeks thereafter, at discontinuation of study treatment and at the 30-day follow-up visit]

   Dyspnea was assessed as the average score of four items: Question 8 of the QLQ-C30 ("Were you short of breath") and Question 3 of the QLQ-C30 ("Were you short of breath when you rested"), Questions 4 ("Were you short of breath when you walked") and 5 ("Were you short of breath when you climbed stairs") of the QLQ-LC13 (or, equivalently, Questions 33, 34 and 35 of the combined QLQ-C30 and QLQ-LC13 questionnaires). Time to deterioration in symptoms is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 28 days. A patient is defined as having a deterioration in symptoms if they have a single visit assessment of 'worsened' with no visit assessment of 'improved' within the next 28 days.

6. Time to Deterioration of Disease-related Symptoms (TDS) by EORTC Quality of Life Questionnaire - Cough [Disease-related symptom assessments are to be administered at screening (within 7 days before the first dose of study medication), every 4 weeks thereafter, at discontinuation of study treatment and at the 30-day follow-up visit]

   Cough was assessed using Question 1 ("How much did you cough") of the QLQ-LC13 (or, equivalently, Question 31 of the combined QLQ-C30 and QLQ-LC13 questionnaires). Time to deterioration in symptoms is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 28 days. A patient is defined as having a deterioration in symptoms if they have a single visit assessment of 'worsened' with no visit assessment of 'improved' within the next 28 days.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Confirmed locally advanced or metastatic NSCLC

• Failure of at least one but not more than two prior chemotherapy regimens

Exclusion Criteria:

• Prior treatment with erlotinib (Tarceva), gefitinib (IRESSA), sunitinib (Sutent), sorafenib (Nexavar)

• Chemotherapy or other type of anti cancer therapy within 4 weeks of study start

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Berkeley	California	United States
2	Research Site	Los Angeles	California	United States
3	Research Site	Santa Rosa	California	United States
4	Research Site	Boynton Beach	Florida	United States
5	Research Site	Fort Myers	Florida	United States
6	Research Site	Jacksonville	Florida	United States
7	Research Site	Port Saint Lucie	Florida	United States
8	Research Site	Wichita	Kansas	United States
9	Research Site	Lexington	Kentucky	United States
10	Research Site	Louisville	Kentucky	United States
11	Research Site	Metairie	Louisiana	United States
12	Research Site	Baltimore	Maryland	United States
13	Research Site	Columbia	Missouri	United States
14	Research Site	Saint Louis	Missouri	United States
15	Research Site	Latham	New York	United States
16	Research Site	Hickory	North Carolina	United States
17	Research Site	Canton	Ohio	United States
18	Research Site	Cincinnati	Ohio	United States
19	Research Site	Greenville	South Carolina	United States
20	Research Site	Chattanooga	Tennessee	United States
21	Research Site	Nashville	Tennessee	United States
22	Research Site	Amarillo	Texas	United States
23	Research Site	Garland	Texas	United States
24	Research Site	Webster	Texas	United States
25	Research Site	Fairfax	Virginia	United States
26	Research Site	Norfolk	Virginia	United States
27	Research Site	Richmond	Virginia	United States
28	Research Site	Burien	Washington	United States
29	Research Site	Yakima	Washington	United States
30	Research Site	Ciudad de Buenos Aires		Argentina
31	Research Site	Córdoba		Argentina
32	Research Site	Gonnet		Argentina
33	Research Site	Ramos Mejía		Argentina
34	Research Site	Rosario		Argentina
35	Research Site	Santa Fe		Argentina
36	Research Site	Ashford		Australia
37	Research Site	Bedford Park		Australia
38	Research Site	Chermside		Australia
39	Research Site	Geelong		Australia
40	Research Site	Hornsby		Australia
41	Research Site	Kogarah		Australia
42	Research Site	Malvern		Australia
43	Research Site	Prahran		Australia
44	Research Site	Wodonga		Australia
45	Research Site	Belo Horizonte		Brazil
46	Research Site	Caxias do Sul		Brazil
47	Research Site	Curitiba		Brazil
48	Research Site	Goiânia		Brazil
49	Research Site	Porto Alegre		Brazil
50	Research Site	Santo André		Brazil
51	Research Site	Sao Paulo		Brazil
52	Research Site	Kelowna	British Columbia	Canada
53	Research Site	Vancouver	British Columbia	Canada
54	Research Site	Winnipeg	Manitoba	Canada
55	Research Site	Oshawa	Ontario	Canada
56	Research Site	Ottawa	Ontario	Canada
57	Research Site	Sault Ste. Marie	Ontario	Canada
58	Research Site	Thunder Bay	Ontario	Canada
59	Research Site	Toronto	Ontario	Canada
60	Research Site	York	Ontario	Canada
61	Research Site	Charlottetown	Prince Edward Island	Canada
62	Research Site	Laval	Quebec	Canada
63	Research Site	Montreal	Quebec	Canada
64	Research Site	Beijing		China
65	Research Site	Dalian		China
66	Research Site	Hangzhou		China
67	Research Site	Nanjing		China
68	Research Site	Nanning		China
69	Research Site	Shanghai		China
70	Research Site	Shenyang		China
71	Research Site	Wuhan		China
72	Research Site	Herlev		Denmark
73	Research Site	København Ø		Denmark
74	Research Site	Næstved		Denmark
75	Research Site	Caen		France
76	Research Site	Clermont Ferrand		France
77	Research Site	Marseille		France
78	Research Site	Paris Cedex 12		France
79	Research Site	RENNES Cedex 9		France
80	Research Site	Vesoul Cedex		France
81	Research Site	Großhansdorf		Germany
82	Research Site	Göttingen		Germany
83	Research Site	Hannover		Germany
84	Research Site	Heidelberg		Germany
85	Research Site	Karlsruhe		Germany
86	Research Site	Löwenstein		Germany
87	Research Site	Mainz		Germany
88	Research Site	Mönchengladbach		Germany
89	Research Site	Ulm		Germany
90	Research Site	Hong Kong		Hong Kong
91	Research Site	Bangalore		India
92	Research Site	Karnataka		India
93	Research Site	New Delhi		India
94	Research Site	Pune		India
95	Research Site	Trivandrum		India
96	Research Site	Bandung		Indonesia
97	Research Site	Jakarta		Indonesia
98	Research Site	Solo		Indonesia
99	Research Site	Ancona		Italy
100	Research Site	Avellino		Italy
101	Research Site	Catania		Italy
102	Research Site	Genova		Italy
103	Research Site	Mantova		Italy
104	Research Site	Milano		Italy
105	Research Site	Orbassano		Italy
106	Research Site	Parma		Italy
107	Research Site	Perugia		Italy
108	Research Site	Roma		Italy
109	Research Site	Rozzano		Italy
110	Research Site	Seoul		Korea, Republic of
111	Research Site	Juchitan		Mexico
112	Research Site	Monterrey		Mexico
113	Research Site	Morelia		Mexico
114	Research Site	Puebla		Mexico
115	Research Site	Saltillo		Mexico
116	Research Site	Zacatecas		Mexico
117	Research Site	Harderwijk		Netherlands
118	Research Site	Nieuwegein		Netherlands
119	Research Site	Rotterdam		Netherlands
120	Research Site	Zwolle		Netherlands
121	Research Site	Bergen		Norway
122	Research Site	Haugesund		Norway
123	Research Site	Kristiansand		Norway
124	Research Site	Oslo		Norway
125	Research Site	Stavanger		Norway
126	Research Site	Tromsø		Norway
127	Research Site	Trondheim		Norway
128	Research Site	Cebu City		Philippines
129	Research Site	Davao City		Philippines
130	Research Site	Manila		Philippines
131	Research Site	Pasay City		Philippines
132	Research Site	Quezon City		Philippines
133	Research Site	Elche(Alicante)		Spain
134	Research Site	Jaén		Spain
135	Research Site	Madrid		Spain
136	Research Site	Mataró(Barcelona)		Spain
137	Research Site	Málaga		Spain
138	Research Site	Pamplona		Spain
139	Research Site	Taichung		Taiwan
140	Research Site	Tainan		Taiwan
141	Research Site	Taipei		Taiwan
142	Research Site	Tao-Yuan		Taiwan
143	Research Site	Bangkok		Thailand
144	Research Site	Chiang Mai		Thailand
145	Research Site	Lampang		Thailand
146	Research Site	Songkla		Thailand
147	Research Site	Birmingham		United Kingdom
148	Research Site	Cambridge		United Kingdom
149	Research Site	Leicester		United Kingdom
150	Research Site	Liverpool		United Kingdom
151	Research Site	Nottingham		United Kingdom
152	Research Site	Sheffield		United Kingdom
153	Research Site	Wolverhampton		United Kingdom

Sponsors and Collaborators

• Genzyme, a Sanofi Company

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Vandetanib_study_57_ZEST_CSP_redacted_SECURE

Publications

None provided.

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT00364351
• Other Study ID Numbers: D4200C00057; EUDRACT No. 2006-000259-16
• First Posted: Aug 15, 2006
• Last Update Posted: Jan 25, 2018
• Last Verified: Jan 1, 2018

• Keywords provided by Genzyme, a Sanofi Company: Non Small Cell Lung Cancer; NSCLC
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Erlotinib Hydrochloride

Study Results

Participant Flow

Recruitment Details	First patient enrolled 24 August 2006, last patient enrolled 31 October 2007, cut off date 26 September 2008. 1574 patients were enrolled in the study.
Pre-assignment Detail	1574 patients were enrolled/screened to the study but only 1240 patients were entered treatment/randomized.

Arm/Group Title	Vandetanib	Erlotinib
Arm/Group Description	Vandetanib 300 mg tablet taken once daily plus a placebo for erlotinib	Erlotinib 150 mg tablet taken once daily plus a placebo for vandetanib
Period Title: Overall Study
STARTED	623	617
COMPLETED	31	34
NOT COMPLETED	592	583

Baseline Characteristics

Arm/Group Title	Vandetanib	Erlotinib	Total
Arm/Group Description	Vandetanib 300 mg	Erlotinib	Total of all reporting groups
Overall Participants	623	617	1240
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	60	61	60
Sex: Female, Male (Count of Participants)
Female	242 38.8%	224 36.3%	466 37.6%
Male	381 61.2%	393 63.7%	774 62.4%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS)
Description	Median time (in weeks) from randomisation until objective disease progression or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable Response Evaluation Criteria In Solid Tumors (RECIST) assessment. Progression was derived according to RECIST 1.0 and is defined as an increase of at least 20% in the total tumour size of measurable lesions over the nadir measurement, unequivocal progression in the non-target lesions or the appearance of one or more new lesions.
Time Frame	progressionRECIST tumour assessments carried out every 4 weeks up to week 16 then every 8 weeks thereafter from randomisation until the date of first documented objective disease progression or date of death from any cause, whichever came first, assessed.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib	Erlotinib
Arm/Group Description	Vandetanib 300 mg	Erlotinib
Measure Participants	623	617
Median (Full Range) [Weeks]	11.3	8.9

2. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival is defined as the time from date of randomization until death. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive (ie their status must be known at the censored date and should not be lost to follow up or unknown).
Time Frame	Time to death in months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib	Erlotinib
Arm/Group Description	Vandetanib 300 mg	Erlotinib
Measure Participants	623	617
Median (Full Range) [Months]	6.9	7.8

3. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	The ORR is the number of patients that are responders ie those patients with a confirmed best objective response of complete response (CR) or partial response (PR) as determined according to RECIST 1.0. CR is defined as the disappearance of all target lesions with no evidence of tumour elsewhere and PR is defined as at least a 30% reduction in the total tumour size of measurable lesions with no new lesions and no progression in the non-target lesions.
Time Frame	RECIST tumour assessments every 4 weeks up to week 16 then every 8 weeks thereafter from randomisation until the date of first documented objective disease progression or date of death from any cause, whichever came first, assessed up to 21 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib	Erlotinib
Arm/Group Description	Vandetanib 300 mg	Erlotinib
Measure Participants	623	617
Number [Participants]	75 12%	74 12%

4. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	Disease control rate is defined as the number of patients who achieved disease control at least 8 weeks following randomisation. Disease control is defined as a best objective response of complete response (CR), partial response (PR) or stable disease (SD) >= 8 weeks as determined according to RECIST 1.0. CR is defined as the disappearance of all target lesions with no evidence of tumour elsewhere, PR is defined as at least a 30% reduction in the total tumour size of measurable lesions with no new lesions and no progression in the non-target lesions and SD >= 8 is assigned to patients who have not responded and have no evidence of progression at least 8 weeks after randomisation.
Time Frame	RECIST tumour assessments carried out every 4 weeks until week 16 then every 8 weeks thereafter (+/- 3 days) from randomisation until objective progression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib	Erlotinib
Arm/Group Description	Vandetanib 300 mg	Erlotinib
Measure Participants	623	617
Number [Participants]	254 40.8%	242 39.2%

5. Secondary Outcome

Title	Time to Deterioration of Disease-related Symptoms (TDS) by EORTC Quality of Life Questionnaire - Pain
Description	Pain was assessed as the average score of two items: Question 9 ("Have you had pain") and 19 ("Did pain interfere with your daily activities") of the QLQ-C30. Time to deterioration in symptoms is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 28 days. A patient is defined as having a deterioration in symptoms if they have a single visit assessment of 'worsened' with no visit assessment of 'improved' within the next 28 days.
Time Frame	Disease-related symptom assessments are to be administered at screening (within 7 days before the first dose of study medication), every 4 weeks thereafter, at discontinuation of study treatment and at the 30-day follow-up visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib	Erlotinib
Arm/Group Description	Vandetanib 300 mg	Erlotinib
Measure Participants	623	617
Median (Inter-Quartile Range) [Weeks]	11.1	9.9

6. Secondary Outcome

Title	Time to Deterioration of Disease-related Symptoms (TDS) by EORTC Quality of Life Questionnaire - Dyspnoea
Description	Dyspnea was assessed as the average score of four items: Question 8 of the QLQ-C30 ("Were you short of breath") and Question 3 of the QLQ-C30 ("Were you short of breath when you rested"), Questions 4 ("Were you short of breath when you walked") and 5 ("Were you short of breath when you climbed stairs") of the QLQ-LC13 (or, equivalently, Questions 33, 34 and 35 of the combined QLQ-C30 and QLQ-LC13 questionnaires). Time to deterioration in symptoms is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 28 days. A patient is defined as having a deterioration in symptoms if they have a single visit assessment of 'worsened' with no visit assessment of 'improved' within the next 28 days.
Time Frame	Disease-related symptom assessments are to be administered at screening (within 7 days before the first dose of study medication), every 4 weeks thereafter, at discontinuation of study treatment and at the 30-day follow-up visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib	Erlotinib
Arm/Group Description	Vandetanib 300 mg	Erlotinib
Measure Participants	623	617
Median (Inter-Quartile Range) [Weeks]	12	12.4

7. Secondary Outcome

Title	Time to Deterioration of Disease-related Symptoms (TDS) by EORTC Quality of Life Questionnaire - Cough
Description	Cough was assessed using Question 1 ("How much did you cough") of the QLQ-LC13 (or, equivalently, Question 31 of the combined QLQ-C30 and QLQ-LC13 questionnaires). Time to deterioration in symptoms is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 28 days. A patient is defined as having a deterioration in symptoms if they have a single visit assessment of 'worsened' with no visit assessment of 'improved' within the next 28 days.
Time Frame	Disease-related symptom assessments are to be administered at screening (within 7 days before the first dose of study medication), every 4 weeks thereafter, at discontinuation of study treatment and at the 30-day follow-up visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib	Erlotinib
Arm/Group Description	Vandetanib 300 mg	Erlotinib
Measure Participants	623	617
Median (Inter-Quartile Range) [Weeks]	15.6	14.1

Adverse Events

Adverse Event Reporting Description	The Safety Analysis Set included all randomized participant who received at least 1 dose of randomized treatment, 623 in vandetanib and 614 in erlotinib.
Arm/Group Title	Vandetanib		Erlotinib
Arm/Group Description	Vandetanib 300 mg.		Erlotinib.
All Cause Mortality
	Vandetanib		Erlotinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Vandetanib		Erlotinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	197/623 (31.6%)		155/614 (25.2%)
Blood and lymphatic system disorders
Anaemia	1/623 (0.2%)		5/614 (0.8%)
Febrile Neutropenia	4/623 (0.6%)		1/614 (0.2%)
Leukocytosis	0/623 (0%)		2/614 (0.3%)
Leukopenia	1/623 (0.2%)		0/614 (0%)
Pancytopenia	0/623 (0%)		1/614 (0.2%)
Thrombocytopenia	1/623 (0.2%)		0/614 (0%)
Thrombotic Thrombocytopenic Purpura	1/623 (0.2%)		0/614 (0%)
Cardiac disorders
Acute Myocardial Infarction	2/623 (0.3%)		0/614 (0%)
Atrial Fibrillation	2/623 (0.3%)		1/614 (0.2%)
Atrial Flutter	1/623 (0.2%)		1/614 (0.2%)
Bradycardia	1/623 (0.2%)		0/614 (0%)
Cardiac Arrest	1/623 (0.2%)		0/614 (0%)
Cardiac Failure	2/623 (0.3%)		0/614 (0%)
Cardio-Respiratory Arrest	3/623 (0.5%)		0/614 (0%)
Cardiopulmonary Failure	1/623 (0.2%)		0/614 (0%)
Myocardial Infarction	6/623 (1%)		2/614 (0.3%)
Pericardial Effusion	1/623 (0.2%)		0/614 (0%)
Postinfarction Angina	1/623 (0.2%)		0/614 (0%)
Right Ventricular Failure	1/623 (0.2%)		0/614 (0%)
Sinus Tachycardia	0/623 (0%)		1/614 (0.2%)
Supraventricular Tachycardia	0/623 (0%)		1/614 (0.2%)
Tachycardia	0/623 (0%)		1/614 (0.2%)
Torsade De Pointes	1/623 (0.2%)		0/614 (0%)
Ventricular Fibrillation	2/623 (0.3%)		0/614 (0%)
Ventricular Tachycardia	1/623 (0.2%)		0/614 (0%)
Eye disorders
Ulcerative Keratitis	1/623 (0.2%)		0/614 (0%)
Gastrointestinal disorders
Abdominal Pain	4/623 (0.6%)		2/614 (0.3%)
Abdominal Wall Haematoma	0/623 (0%)		1/614 (0.2%)
Colitis Ischaemic	0/623 (0%)		1/614 (0.2%)
Constipation	0/623 (0%)		1/614 (0.2%)
Diarrhoea	19/623 (3%)		8/614 (1.3%)
Dysphagia	4/623 (0.6%)		4/614 (0.7%)
Enteritis	1/623 (0.2%)		0/614 (0%)
Gastritis	1/623 (0.2%)		0/614 (0%)
Gastrointestinal Haemorrhage	1/623 (0.2%)		0/614 (0%)
Gastrointestinal Ulcer Haemorrhage	0/623 (0%)		1/614 (0.2%)
Haemorrhoids	1/623 (0.2%)		0/614 (0%)
Inguinal Hernia Strangulated	0/623 (0%)		1/614 (0.2%)
Nausea	5/623 (0.8%)		5/614 (0.8%)
Oesophageal Stenosis	0/623 (0%)		1/614 (0.2%)
Pancreatitis	0/623 (0%)		1/614 (0.2%)
Small Intestinal Obstruction	1/623 (0.2%)		0/614 (0%)
Vomiting	9/623 (1.4%)		9/614 (1.5%)
General disorders
Asthenia	4/623 (0.6%)		2/614 (0.3%)
Chest Pain	2/623 (0.3%)		1/614 (0.2%)
Chills	1/623 (0.2%)		0/614 (0%)
Complication Associated With Device	0/623 (0%)		1/614 (0.2%)
Death	3/623 (0.5%)		0/614 (0%)
Fatigue	3/623 (0.5%)		4/614 (0.7%)
General Physical Health Deterioration	3/623 (0.5%)		0/614 (0%)
Malaise	0/623 (0%)		1/614 (0.2%)
Mucosal Inflammation	1/623 (0.2%)		0/614 (0%)
Multiple Organ Dysfunction Syndrome	0/623 (0%)		1/614 (0.2%)
Non-Cardiac Chest Pain	0/623 (0%)		1/614 (0.2%)
Oedema	0/623 (0%)		1/614 (0.2%)
Oedema Peripheral	0/623 (0%)		1/614 (0.2%)
Pain	0/623 (0%)		1/614 (0.2%)
Pyrexia	7/623 (1.1%)		6/614 (1%)
Sudden Death	1/623 (0.2%)		3/614 (0.5%)
Hepatobiliary disorders
Biliary Colic	1/623 (0.2%)		0/614 (0%)
Immune system disorders
Anaphylactic Shock	1/623 (0.2%)		0/614 (0%)
Infections and infestations
Abscess Limb	1/623 (0.2%)		0/614 (0%)
Arthritis Bacterial	1/623 (0.2%)		0/614 (0%)
Atypical Pneumonia	0/623 (0%)		1/614 (0.2%)
Bronchitis	2/623 (0.3%)		2/614 (0.3%)
Cellulitis	1/623 (0.2%)		1/614 (0.2%)
Clostridium Colitis	0/623 (0%)		1/614 (0.2%)
Conjunctivitis	1/623 (0.2%)		1/614 (0.2%)
Diverticulitis	1/623 (0.2%)		0/614 (0%)
Empyema	0/623 (0%)		1/614 (0.2%)
Erysipelas	0/623 (0%)		1/614 (0.2%)
Gastroenteritis	1/623 (0.2%)		0/614 (0%)
Gastroenteritis Clostridial	1/623 (0.2%)		0/614 (0%)
Genital Infection	0/623 (0%)		1/614 (0.2%)
Hepatobiliary Infection	1/623 (0.2%)		0/614 (0%)
Herpes Zoster	0/623 (0%)		1/614 (0.2%)
Infection	1/623 (0.2%)		1/614 (0.2%)
Infective Exacerbation Of Chronic Obstructive Airways Disease	2/623 (0.3%)		1/614 (0.2%)
Lower Respiratory Tract Infection	7/623 (1.1%)		6/614 (1%)
Lung Infection	1/623 (0.2%)		0/614 (0%)
Mycobacterial Infection	1/623 (0.2%)		0/614 (0%)
Neutropenic Infection	1/623 (0.2%)		0/614 (0%)
Pleural Infection	0/623 (0%)		1/614 (0.2%)
Pleural Infection Bacterial	0/623 (0%)		1/614 (0.2%)
Pneumococcal Sepsis	0/623 (0%)		1/614 (0.2%)
Pneumonia	27/623 (4.3%)		22/614 (3.6%)
Pneumonia Haemophilus	0/623 (0%)		1/614 (0.2%)
Pulmonary Sepsis	1/623 (0.2%)		0/614 (0%)
Pulmonary Tuberculosis	2/623 (0.3%)		1/614 (0.2%)
Pyelonephritis	0/623 (0%)		1/614 (0.2%)
Respiratory Tract Infection	5/623 (0.8%)		4/614 (0.7%)
Sepsis	1/623 (0.2%)		4/614 (0.7%)
Septic Shock	1/623 (0.2%)		1/614 (0.2%)
Streptococcal Bacteraemia	1/623 (0.2%)		0/614 (0%)
Subcutaneous Abscess	1/623 (0.2%)		0/614 (0%)
Urinary Tract Infection	6/623 (1%)		1/614 (0.2%)
Viral Upper Respiratory Tract Infection	1/623 (0.2%)		0/614 (0%)
Injury, poisoning and procedural complications
Fall	1/623 (0.2%)		0/614 (0%)
Femoral Neck Fracture	1/623 (0.2%)		0/614 (0%)
Femur Fracture	2/623 (0.3%)		1/614 (0.2%)
Gastroenteritis Radiation	0/623 (0%)		1/614 (0.2%)
Head Injury	0/623 (0%)		1/614 (0.2%)
Hip Fracture	1/623 (0.2%)		0/614 (0%)
Humerus Fracture	0/623 (0%)		1/614 (0.2%)
Overdose	1/623 (0.2%)		0/614 (0%)
Post Procedural Haemorrhage	1/623 (0.2%)		0/614 (0%)
Procedural Pain	0/623 (0%)		1/614 (0.2%)
Radiation Injury	0/623 (0%)		1/614 (0.2%)
Spinal Compression Fracture	2/623 (0.3%)		0/614 (0%)
Subdural Haematoma	0/623 (0%)		1/614 (0.2%)
Vascular Graft Occlusion	0/623 (0%)		1/614 (0.2%)
Investigations
Body Temperature Increased	0/623 (0%)		1/614 (0.2%)
C-Reactive Protein Increased	0/623 (0%)		2/614 (0.3%)
Electrocardiogram Qt Prolonged	2/623 (0.3%)		0/614 (0%)
Electrocardiogram St-T Change	1/623 (0.2%)		0/614 (0%)
Electrocardiogram T Wave Inversion	1/623 (0.2%)		0/614 (0%)
International Normalised Ratio Increased	1/623 (0.2%)		0/614 (0%)
Platelet Count Decreased	1/623 (0.2%)		0/614 (0%)
Weight Decreased	0/623 (0%)		1/614 (0.2%)
Metabolism and nutrition disorders
Cachexia	0/623 (0%)		1/614 (0.2%)
Decreased Appetite	3/623 (0.5%)		4/614 (0.7%)
Dehydration	7/623 (1.1%)		4/614 (0.7%)
Diabetes Mellitus	0/623 (0%)		1/614 (0.2%)
Diabetes Mellitus Inadequate Control	0/623 (0%)		1/614 (0.2%)
Hypercalcaemia	0/623 (0%)		1/614 (0.2%)
Hypoglycaemia	2/623 (0.3%)		0/614 (0%)
Hypokalaemia	2/623 (0.3%)		0/614 (0%)
Hyponatraemia	3/623 (0.5%)		0/614 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/623 (0%)		3/614 (0.5%)
Back Pain	1/623 (0.2%)		0/614 (0%)
Bone Pain	1/623 (0.2%)		0/614 (0%)
Muscular Weakness	1/623 (0.2%)		3/614 (0.5%)
Musculoskeletal Chest Pain	3/623 (0.5%)		0/614 (0%)
Neck Pain	1/623 (0.2%)		0/614 (0%)
Pain In Extremity	0/623 (0%)		3/614 (0.5%)
Spinal Pain	1/623 (0.2%)		0/614 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-Cell Small Lymphocytic Lymphoma	0/623 (0%)		1/614 (0.2%)
Cancer Pain	3/623 (0.5%)		4/614 (0.7%)
Lymphangiosis Carcinomatosa	1/623 (0.2%)		0/614 (0%)
Malignant Pleural Effusion	1/623 (0.2%)		0/614 (0%)
Prostate Cancer	1/623 (0.2%)		1/614 (0.2%)
Nervous system disorders
Altered State Of Consciousness	1/623 (0.2%)		1/614 (0.2%)
Aphasia	1/623 (0.2%)		0/614 (0%)
Ataxia	0/623 (0%)		1/614 (0.2%)
Cerebral Infarction	0/623 (0%)		1/614 (0.2%)
Cerebral Ischaemia	2/623 (0.3%)		0/614 (0%)
Cerebral Thrombosis	1/623 (0.2%)		0/614 (0%)
Cerebrovascular Accident	1/623 (0.2%)		3/614 (0.5%)
Dizziness	3/623 (0.5%)		1/614 (0.2%)
Dysarthria	0/623 (0%)		1/614 (0.2%)
Headache	2/623 (0.3%)		0/614 (0%)
Hemiparesis	1/623 (0.2%)		0/614 (0%)
Lethargy	1/623 (0.2%)		0/614 (0%)
Paralysis Recurrent Laryngeal Nerve	0/623 (0%)		1/614 (0.2%)
Psychomotor Hyperactivity	0/623 (0%)		1/614 (0.2%)
Seizure	7/623 (1.1%)		3/614 (0.5%)
Somnolence	0/623 (0%)		2/614 (0.3%)
Speech Disorder	0/623 (0%)		1/614 (0.2%)
Spinal Cord Compression	0/623 (0%)		2/614 (0.3%)
Syncope	1/623 (0.2%)		4/614 (0.7%)
Product Issues
Device Failure	1/623 (0.2%)		0/614 (0%)
Psychiatric disorders
Anxiety	1/623 (0.2%)		0/614 (0%)
Completed Suicide	1/623 (0.2%)		0/614 (0%)
Confusional State	1/623 (0.2%)		4/614 (0.7%)
Insomnia	0/623 (0%)		1/614 (0.2%)
Mental Status Changes	1/623 (0.2%)		1/614 (0.2%)
Renal and urinary disorders
Acute Kidney Injury	0/623 (0%)		1/614 (0.2%)
Calculus Urinary	0/623 (0%)		1/614 (0.2%)
Hydronephrosis	1/623 (0.2%)		0/614 (0%)
Nephrolithiasis	1/623 (0.2%)		1/614 (0.2%)
Renal Failure	0/623 (0%)		1/614 (0.2%)
Tubulointerstitial Nephritis	1/623 (0.2%)		0/614 (0%)
Urinary Retention	1/623 (0.2%)		0/614 (0%)
Respiratory, thoracic and mediastinal disorders
Acquired Tracheo-Oesophageal Fistula	1/623 (0.2%)		1/614 (0.2%)
Acute Respiratory Failure	0/623 (0%)		1/614 (0.2%)
Aspiration	0/623 (0%)		1/614 (0.2%)
Asthmatic Crisis	0/623 (0%)		1/614 (0.2%)
Atelectasis	0/623 (0%)		1/614 (0.2%)
Bronchial Fistula	0/623 (0%)		1/614 (0.2%)
Chronic Obstructive Pulmonary Disease	0/623 (0%)		1/614 (0.2%)
Cough	4/623 (0.6%)		2/614 (0.3%)
Dyspnoea	13/623 (2.1%)		20/614 (3.3%)
Haemoptysis	1/623 (0.2%)		11/614 (1.8%)
Hypoxia	0/623 (0%)		2/614 (0.3%)
Interstitial Lung Disease	1/623 (0.2%)		0/614 (0%)
Laryngeal Oedema	1/623 (0.2%)		0/614 (0%)
Lung Infiltration	1/623 (0.2%)		0/614 (0%)
Pleural Effusion	1/623 (0.2%)		2/614 (0.3%)
Pleural Fibrosis	0/623 (0%)		1/614 (0.2%)
Pleurisy	1/623 (0.2%)		0/614 (0%)
Pneumonia Aspiration	2/623 (0.3%)		1/614 (0.2%)
Pneumonitis	2/623 (0.3%)		3/614 (0.5%)
Pneumothorax	0/623 (0%)		3/614 (0.5%)
Pulmonary Embolism	8/623 (1.3%)		6/614 (1%)
Pulmonary Haemorrhage	1/623 (0.2%)		0/614 (0%)
Respiratory Distress	1/623 (0.2%)		0/614 (0%)
Respiratory Failure	3/623 (0.5%)		0/614 (0%)
Stridor	1/623 (0.2%)		0/614 (0%)
Skin and subcutaneous tissue disorders
Acne	0/623 (0%)		1/614 (0.2%)
Angioedema	0/623 (0%)		1/614 (0.2%)
Dermatitis Acneiform	0/623 (0%)		3/614 (0.5%)
Dermatitis Exfoliative	2/623 (0.3%)		0/614 (0%)
Eczema Asteatotic	1/623 (0.2%)		0/614 (0%)
Erythema	1/623 (0.2%)		1/614 (0.2%)
Erythema Multiforme	1/623 (0.2%)		0/614 (0%)
Palmar-Plantar Erythrodysaesthesia Syndrome	1/623 (0.2%)		0/614 (0%)
Photosensitivity Reaction	3/623 (0.5%)		1/614 (0.2%)
Rash	7/623 (1.1%)		2/614 (0.3%)
Rash Erythematous	1/623 (0.2%)		0/614 (0%)
Rash Maculo-Papular	1/623 (0.2%)		0/614 (0%)
Rash Papular	0/623 (0%)		2/614 (0.3%)
Surgical and medical procedures
Thoracotomy	0/623 (0%)		1/614 (0.2%)
Vascular disorders
Deep Vein Thrombosis	1/623 (0.2%)		5/614 (0.8%)
Haematoma	0/623 (0%)		1/614 (0.2%)
Hypertension	3/623 (0.5%)		1/614 (0.2%)
Hypertensive Crisis	1/623 (0.2%)		0/614 (0%)
Hypotension	0/623 (0%)		3/614 (0.5%)
Hypovolaemic Shock	0/623 (0%)		1/614 (0.2%)
Jugular Vein Thrombosis	0/623 (0%)		1/614 (0.2%)
Orthostatic Hypotension	0/623 (0%)		1/614 (0.2%)
Peripheral Arterial Occlusive Disease	1/623 (0.2%)		0/614 (0%)
Peripheral Ischaemia	1/623 (0.2%)		0/614 (0%)
Subclavian Vein Thrombosis	1/623 (0.2%)		1/614 (0.2%)
Other (Not Including Serious) Adverse Events
	Vandetanib		Erlotinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	539/623 (86.5%)		542/614 (88.3%)
Gastrointestinal disorders
Constipation	58/623 (9.3%)		87/614 (14.2%)
Diarrhoea	300/623 (48.2%)		232/614 (37.8%)
Dyspepsia	29/623 (4.7%)		31/614 (5%)
Nausea	138/623 (22.2%)		131/614 (21.3%)
Stomatitis	33/623 (5.3%)		33/614 (5.4%)
Vomiting	85/623 (13.6%)		91/614 (14.8%)
General disorders
Asthenia	50/623 (8%)		59/614 (9.6%)
Fatigue	119/623 (19.1%)		109/614 (17.8%)
Oedema Peripheral	21/623 (3.4%)		34/614 (5.5%)
Pyrexia	44/623 (7.1%)		50/614 (8.1%)
Infections and infestations
Paronychia	12/623 (1.9%)		31/614 (5%)
Investigations
Weight Decreased	33/623 (5.3%)		29/614 (4.7%)
Metabolism and nutrition disorders
Anorexia	114/623 (18.3%)		123/614 (20%)
Musculoskeletal and connective tissue disorders
Back Pain	37/623 (5.9%)		40/614 (6.5%)
Musculoskeletal Chest Pain	33/623 (5.3%)		24/614 (3.9%)
Nervous system disorders
Dizziness	37/623 (5.9%)		40/614 (6.5%)
Headache	55/623 (8.8%)		40/614 (6.5%)
Psychiatric disorders
Insomnia	59/623 (9.5%)		40/614 (6.5%)
Renal and urinary disorders
Proteinuria	33/623 (5.3%)		8/614 (1.3%)
Respiratory, thoracic and mediastinal disorders
Cough	78/623 (12.5%)		92/614 (15%)
Dyspnoea	84/623 (13.5%)		70/614 (11.4%)
Haemoptysis	31/623 (5%)		39/614 (6.4%)
Skin and subcutaneous tissue disorders
Acne	45/623 (7.2%)		50/614 (8.1%)
Dermatitis Acneiform	75/623 (12%)		103/614 (16.8%)
Dry Skin	60/623 (9.6%)		84/614 (13.7%)
Pruritus	38/623 (6.1%)		67/614 (10.9%)
Rash	169/623 (27.1%)		232/614 (37.8%)
Vascular disorders
Hypertension	99/623 (15.9%)		14/614 (2.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.