ZD6474 (ZACTIMA™) Phase III Study in EGFR Failures

• Sponsor: Genzyme, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00404924
• Collaborator: (none)
• Enrollment: 1,140
• Locations: 103
• Arms: 2
• Duration (Months): 96
• Patients Per Site: 11.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study is being carried out to assess if adding ZD6474 to best supportive care (BSC) is more effective than best supportive care alone, for the treatment of patients with non-small cell lung cancer, whose disease has recurred after previous chemotherapy and an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI). ZD6474 is a new anti-cancer drug in development that works in a different way to standard chemotherapy drugs. It targets the growth of new blood vessels to a tumour and thereby might slow the rate at which the tumour may grow. Early studies indicate that ZD6474 has a positive effect on the time that a tumour may take to progress to a further stage. Approximately 930 patients will take part in this study. It will be conducted in hospitals and clinics in North and South America, Europe and Asia.

Condition or Disease	Intervention/Treatment	Phase
Non-Small-Cell Lung Carcinoma	Drug: ZD6474 (vandetanib); Other: Best Supportive Care	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1140 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III Study to Assess the Efficacy of ZD6474 (ZACTIMA™) Plus Best Supportive Care Versus Best Supportive Care in Patients With Locally Advanced or Metastatic (Stage IIIB-IV) Non-Small Cell Lung Cancer After Therapy With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI)
• Study Start Date: Nov 1, 2006
• Actual Primary Completion Date: Oct 1, 2009
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 1 Best Supportive Care	Other: Best Supportive Care; standard of care
Experimental: 2 Vandetanib + Best Supportive Care	Drug: ZD6474 (vandetanib); once daily oral tablet; Other Names: ZACTIMA™ ; Other: Best Supportive Care; standard of care

Outcome Measures

Primary Outcome Measures

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

   Overall Survival (OS) is defined as the time from date of randomization until death. Any blinded/unknown patient which 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).

Secondary Outcome Measures

1. Progression-Free Survival (PFS) [RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression]

   Median time (in months) from randomisation until objective disease progression (determined by RECIST assessments) or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment

2. Objective Response Rate (ORR) [Each patient was assessed for objective response from the sequence of RECIST scan data up to data cut off. RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression.]

   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 defined by RECIST criteria. The categories for best objective response are CR, PR, stable disease (SD)>= 8 weeks, progressive disease (PD) or NE.

3. Disease Control Rate (DCR) [RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression]

   Disease control rate is defined as the number of patients who achieved disease control at 8 weeks following randomisation. Disease control at 8 weeks is defined as a best objective response of complete response (CR), partial response (PR) or stable disease (SD) >= 8 weeks

4. Duration of Response (DoR) [RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression]

   Response is defined as a confirmed best objective response of CR or PR. Duration of response is defined as time from the date of first documented response until date of documented progression or death in the absence of disease progression (provided death is within 3 months of last RECIST assessment)

5. Time to Deterioration of Disease-related Symptoms (TDS) by Questionnaire - the Lung Cancer Subscale (LCS) a Selection of the FACT-L Focusing on Symptoms of Lung Cancer Plus Pain and Fatigue (LCS-PF) [Disease-related symptom assessments are to be administered at screening (within 7 days before the first dose of study medication) and every 4 weeks thereafter, at discontinuation of study treatment and at the 30-day follow-up visit]

   Time to deterioration in symptoms is defined as the interval from the date of randomization to the first assessment of 'worsened' with no visit assessment of 'improved' within the next 28 days. Where assessment is by a selection of questions from the Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L) questionnaire.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients with Non-small cell lung cancer for which the standard cancer treatments of surgery, chemotherapy, radiation or other anticancer drugs are no longer appropriate treatments for you.

Exclusion Criteria:

• Patients who have had standard cancer treatments of surgery, chemotherapy or other systemic anti-cancer therapy within 4 weeks before start of study therapy.

• Three or more prior chemotherapy regimens.

• Significant cardiovascular events.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Tucson	Arizona	United States
2	Research Site	Germantown	Tennessee	United States
3	Research Site	Bahia Blanca		Argentina
4	Research Site	Ciudad de Buenos Aires		Argentina
5	Research Site	La Plata		Argentina
6	Research Site	Rosario		Argentina
7	Research Site	San Miguel de Tucuman		Argentina
8	Research Site	Santa Fe		Argentina
9	Research Site	Fitzroy		Australia
10	Research Site	Perth		Australia
11	Research Site	St. Leonards		Australia
12	Research Site	Tugan		Australia
13	Research Site	Woodville South		Australia
14	Research Site	Linz		Austria
15	Research Site	Salzburg		Austria
16	Research Site	Vienna		Austria
17	Research Site	Antwerpen		Belgium
18	Research Site	Brussels (Woluwé-St-Lambert)		Belgium
19	Research Site	Charleroi		Belgium
20	Research Site	Edegem		Belgium
21	Research Site	Gent		Belgium
22	Research Site	Leuven		Belgium
23	Research Site	Liège		Belgium
24	Research Site	Edmonton	Alberta	Canada
25	Research Site	Oshawa	Ontario	Canada
26	Research Site	Toronto	Ontario	Canada
27	Research Site	Montreal	Quebec	Canada
28	Research Site	Beijing		China
29	Research Site	Chengdu		China
30	Research Site	Dalian		China
31	Research Site	Guangzhou		China
32	Research Site	Nanjing		China
33	Research Site	Shanghai		China
34	Research Site	Wuhan		China
35	Research Site	Xi'an		China
36	Research Site	Brest Cedex		France
37	Research Site	Caen Cedex		France
38	Research Site	Lyon Cedex		France
39	Research Site	Marseille Cedex 9		France
40	Research Site	Nice Cedex		France
41	Research Site	Pierre Benite Cedex		France
42	Research Site	Toulon Armees		France
43	Research Site	Bad Berka		Germany
44	Research Site	Donaustauf		Germany
45	Research Site	Frankfurt		Germany
46	Research Site	Gauting		Germany
47	Research Site	Göttingen		Germany
48	Research Site	Halle		Germany
49	Research Site	Hannover		Germany
50	Research Site	Karlsruhe		Germany
51	Research Site	Leipzig		Germany
52	Research Site	Löwenstein		Germany
53	Research Site	Mannheim		Germany
54	Research Site	München		Germany
55	Research Site	Hong Kong		Hong Kong
56	Research Site	Jerusalem		Israel
57	Research Site	Kfar Saba		Israel
58	Research Site	Tel-Hashomer		Israel
59	Research Site	Zerifin		Israel
60	Research Site	Ancona		Italy
61	Research Site	Bologna		Italy
62	Research Site	Catania		Italy
63	Research Site	Genova		Italy
64	Research Site	Milano		Italy
65	Research Site	Orbassano		Italy
66	Research Site	Parma		Italy
67	Research Site	Roma		Italy
68	Research Site	Rozzano		Italy
69	Research Site	S.Andrea delle Fratte		Italy
70	Research Site	Sondalo		Italy
71	Research Site	Udine		Italy
72	Research Site	Goyang-si		Korea, Republic of
73	Research Site	Seongnam		Korea, Republic of
74	Research Site	Seoul		Korea, Republic of
75	Research Site	Suwon		Korea, Republic of
76	Research Site	México		Mexico
77	Research Site	Zapopan		Mexico
78	Research Site	St Maartenskliniek		Netherlands
79	Research Site	Lima		Peru
80	Research Site	Cebu City		Philippines
81	Research Site	Manila		Philippines
82	Research Site	Quezon City		Philippines
83	Research Site	Singapore		Singapore
84	Research Site	Baracaldo(Vizcaya)		Spain
85	Research Site	Barcelona		Spain
86	Research Site	Santander		Spain
87	Research Site	Valencia		Spain
88	Research Site	Changhua		Taiwan
89	Research Site	Kao Hsiung		Taiwan
90	Research Site	Kaohsiung Hsien		Taiwan
91	Research Site	Kaohsiung		Taiwan
92	Research Site	Liou Ying Township		Taiwan
93	Research Site	Taichung		Taiwan
94	Research Site	Taipei		Taiwan
95	Research Site	Tao-Yuan		Taiwan
96	Research Site	Bangkok		Thailand
97	Research Site	Chiang Mai		Thailand
98	Research Site	Khon Kaen		Thailand
99	Research Site	Birmingham		United Kingdom
100	Research Site	Chelmsford		United Kingdom
101	Research Site	Dundee		United Kingdom
102	Research Site	Maidstone		United Kingdom
103	Research Site	Manchester		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:

• Related Info
• CSR-D4200C00044.pdf

Publications

None provided.

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT00404924
• Other Study ID Numbers: D4200C00044; EUDRACT Number 2006-002384-12
• First Posted: Nov 29, 2006
• Last Update Posted: Sep 30, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by Genzyme, a Sanofi Company: Non-Small-Cell Lung Carcinoma; Adenocarcinoma; Squamous Cell Carcinoma; Large Cell Carcinoma
• Additional relevant MeSH terms: Carcinoma; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Study Results

Participant Flow

Recruitment Details	First patient enrolled 08 November 2006, last patient enrolled 09 October 2008, cut off date 19 October 2009. 1168 patients were enrolled in the study.

Arm/Group Title	Vandetanib 300 mg	Placebo
Arm/Group Description	vandetanib (300 mg daily) plus best supportive care	Placebo plus best supportive care
Period Title: Overall Study
STARTED	617	307
COMPLETED	14	1
NOT COMPLETED	603	306

Baseline Characteristics

Arm/Group Title	Vandetanib 300 mg	Placebo	Total
Arm/Group Description	vandetanib (300 mg daily) plus best supportive care	Placebo plus best supportive care	Total of all reporting groups
Overall Participants	617	307	924
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	59.8	60.6	60
Sex: Female, Male (Count of Participants)
Female	329 53.3%	160 52.1%	489 52.9%
Male	288 46.7%	147 47.9%	435 47.1%

Outcome Measures

1. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	Median time (in months) from randomisation until objective disease progression (determined by RECIST assessments) or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment
Time Frame	RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 300 mg	Placebo
Arm/Group Description	vandetanib (300 mg daily) plus best supportive care	Placebo plus best supportive care
Measure Participants	617	307
Median (95% Confidence Interval) [month]	1.9	1.8

2. 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 defined by RECIST criteria. The categories for best objective response are CR, PR, stable disease (SD)>= 8 weeks, progressive disease (PD) or NE.
Time Frame	Each patient was assessed for objective response from the sequence of RECIST scan data up to data cut off. RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 300 mg	Placebo
Arm/Group Description	vandetanib (300 mg daily) plus best supportive care	Placebo plus best supportive care
Measure Participants	617	307
Number [Participants]	16 2.6%	2 0.7%

3. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	Disease control rate is defined as the number of patients who achieved disease control at 8 weeks following randomisation. Disease control at 8 weeks is defined as a best objective response of complete response (CR), partial response (PR) or stable disease (SD) >= 8 weeks
Time Frame	RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 300 mg	Placebo
Arm/Group Description	vandetanib (300 mg daily) plus best supportive care	Placebo plus best supportive care
Measure Participants	617	307
Number [Participants]	189 30.6%	48 15.6%

4. Secondary Outcome

Title	Duration of Response (DoR)
Description	Response is defined as a confirmed best objective response of CR or PR. Duration of response is defined as time from the date of first documented response until date of documented progression or death in the absence of disease progression (provided death is within 3 months of last RECIST assessment)
Time Frame	RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 300 mg	Placebo
Arm/Group Description	vandetanib (300 mg daily) plus best supportive care	Placebo plus best supportive care
Measure Participants	16	2
Median (95% Confidence Interval) [Weeks]	23.9	24.3

5. Primary Outcome

Title	Overall Survival (OS)
Description	Overall Survival (OS) is defined as the time from date of randomization until death. Any blinded/unknown patient which 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 300 mg	Placebo
Arm/Group Description	vandetanib (300 mg daily) plus best supportive care	Placebo plus best supportive care
Measure Participants	617	307
Median (95% Confidence Interval) [Months]	8.5	7.8

6. Secondary Outcome

Title	Time to Deterioration of Disease-related Symptoms (TDS) by Questionnaire - the Lung Cancer Subscale (LCS) a Selection of the FACT-L Focusing on Symptoms of Lung Cancer Plus Pain and Fatigue (LCS-PF)
Description	Time to deterioration in symptoms is defined as the interval from the date of randomization to the first assessment of 'worsened' with no visit assessment of 'improved' within the next 28 days. Where assessment is by a selection of questions from the Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L) questionnaire.
Time Frame	Disease-related symptom assessments are to be administered at screening (within 7 days before the first dose of study medication) and 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 300 mg	Placebo
Arm/Group Description	vandetanib (300 mg daily) plus best supportive care	Placebo plus best supportive care
Measure Participants	617	307
Median (Inter-Quartile Range) [weeks]	6.1	7.1

Adverse Events

Adverse Event Reporting Description	The Safety Analysis Set included 922 patients (619 vandetanib & 303 placebo), which represents more than 99% of all randomized pts. 2 (1 in each arm) were excluded from the SAS as they were not dosed. Additionally 3 pts randomized to receive placebo received at least one dose of vandetanib, these 3 pts are included in the vandetanib arm in the SAS
Arm/Group Title	Vandetanib		Placebo
Arm/Group Description	Vandetanib 300 mg		Placebo
All Cause Mortality
	Vandetanib		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Vandetanib		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	160/619 (25.8%)		63/303 (20.8%)
Blood and lymphatic system disorders
Febrile Neutropenia	3/619 (0.5%)		0/303 (0%)
Anaemia	0/619 (0%)		2/303 (0.7%)
Thrombocytopenia	2/619 (0.3%)		2/303 (0.7%)
Leukopenia	0/619 (0%)		1/303 (0.3%)
Neutropenia	1/619 (0.2%)		1/303 (0.3%)
Cardiac disorders
Atrial Fibrillation	2/619 (0.3%)		0/303 (0%)
Cardiac Failure	2/619 (0.3%)		0/303 (0%)
Myocardial Infarction	2/619 (0.3%)		1/303 (0.3%)
Angina Pectoris	0/619 (0%)		1/303 (0.3%)
Arrhythmia	1/619 (0.2%)		0/303 (0%)
Cardiac Arrest	1/619 (0.2%)		0/303 (0%)
Cardiac Valve Disease	1/619 (0.2%)		0/303 (0%)
Pericardial Effusion	0/619 (0%)		1/303 (0.3%)
Ear and labyrinth disorders
Deafness	1/619 (0.2%)		0/303 (0%)
Vertigo	0/619 (0%)		1/303 (0.3%)
Endocrine disorders
Hyperthyroidism	1/619 (0.2%)		0/303 (0%)
Eye disorders
Diplopia	1/619 (0.2%)		0/303 (0%)
Vision Blurred	1/619 (0.2%)		0/303 (0%)
Visual Acuity Reduced	1/619 (0.2%)		0/303 (0%)
Gastrointestinal disorders
Diarrhoea	8/619 (1.3%)		0/303 (0%)
Vomiting	4/619 (0.6%)		3/303 (1%)
Nausea	2/619 (0.3%)		1/303 (0.3%)
Abdominal Distension	1/619 (0.2%)		0/303 (0%)
Abdominal Pain	1/619 (0.2%)		0/303 (0%)
Ascites	0/619 (0%)		1/303 (0.3%)
Constipation	1/619 (0.2%)		0/303 (0%)
Duodenal Ulcer	1/619 (0.2%)		0/303 (0%)
Enteritis	1/619 (0.2%)		0/303 (0%)
Gastrointestinal Perforation	0/619 (0%)		1/303 (0.3%)
Gastrooesophageal Reflux Disease	1/619 (0.2%)		0/303 (0%)
Gingival Pain	1/619 (0.2%)		0/303 (0%)
Ileus Paralytic	1/619 (0.2%)		0/303 (0%)
Intestinal Haemorrhage	0/619 (0%)		1/303 (0.3%)
Intestinal Perforation	0/619 (0%)		1/303 (0.3%)
Neutropenic Colitis	1/619 (0.2%)		0/303 (0%)
Pancreatitis	1/619 (0.2%)		0/303 (0%)
Paraesthesia Oral	0/619 (0%)		1/303 (0.3%)
Pneumatosis Intestinalis	1/619 (0.2%)		0/303 (0%)
Proctalgia	1/619 (0.2%)		0/303 (0%)
Subileus	0/619 (0%)		1/303 (0.3%)
General disorders
Asthenia	5/619 (0.8%)		1/303 (0.3%)
Death	3/619 (0.5%)		0/303 (0%)
Fatigue	3/619 (0.5%)		1/303 (0.3%)
Pyrexia	3/619 (0.5%)		3/303 (1%)
Chest Pain	1/619 (0.2%)		0/303 (0%)
General Physical Health Deterioration	1/619 (0.2%)		0/303 (0%)
Malaise	0/619 (0%)		1/303 (0.3%)
Pain	1/619 (0.2%)		0/303 (0%)
Hepatobiliary disorders
Bile Duct Stenosis	0/619 (0%)		1/303 (0.3%)
Cytolytic Hepatitis	1/619 (0.2%)		0/303 (0%)
Immune system disorders
Drug Hypersensitivity	2/619 (0.3%)		0/303 (0%)
Anaphylactic Reaction	1/619 (0.2%)		0/303 (0%)
Infections and infestations
Pneumonia	21/619 (3.4%)		6/303 (2%)
Sepsis	3/619 (0.5%)		1/303 (0.3%)
Lung Infection	2/619 (0.3%)		1/303 (0.3%)
Urinary Tract Infection	2/619 (0.3%)		1/303 (0.3%)
Arthritis Bacterial	0/619 (0%)		1/303 (0.3%)
Bacterial Sepsis	0/619 (0%)		1/303 (0.3%)
Bronchitis	0/619 (0%)		1/303 (0.3%)
Catheter Site Infection	1/619 (0.2%)		1/303 (0.3%)
Cellulitis	1/619 (0.2%)		0/303 (0%)
Clostridial Infection	1/619 (0.2%)		0/303 (0%)
Empyema	0/619 (0%)		1/303 (0.3%)
Gastroenteritis	1/619 (0.2%)		0/303 (0%)
Injection Site Abscess	1/619 (0.2%)		0/303 (0%)
Lobar Pneumonia	1/619 (0.2%)		0/303 (0%)
Lower Respiratory Tract Infection	1/619 (0.2%)		1/303 (0.3%)
Pharyngitis	1/619 (0.2%)		0/303 (0%)
Staphylococcal Sepsis	1/619 (0.2%)		0/303 (0%)
Subcutaneous Abscess	1/619 (0.2%)		0/303 (0%)
Tracheitis	1/619 (0.2%)		0/303 (0%)
Upper Respiratory Tract Infection	1/619 (0.2%)		1/303 (0.3%)
Urosepsis	1/619 (0.2%)		0/303 (0%)
Injury, poisoning and procedural complications
Femur Fracture	2/619 (0.3%)		0/303 (0%)
Femoral Neck Fracture	1/619 (0.2%)		0/303 (0%)
Joint Dislocation	1/619 (0.2%)		0/303 (0%)
Multiple Injuries	1/619 (0.2%)		0/303 (0%)
Pneumothorax Traumatic	1/619 (0.2%)		0/303 (0%)
Wound	1/619 (0.2%)		0/303 (0%)
Wrist Fracture	1/619 (0.2%)		0/303 (0%)
Electrocardiogram T Wave Inversion	1/619 (0.2%)		0/303 (0%)
Lipase Increased	1/619 (0.2%)		0/303 (0%)
Neutrophil Count Decreased	1/619 (0.2%)		0/303 (0%)
Metabolism and nutrition disorders
Dehydration	4/619 (0.6%)		1/303 (0.3%)
Decreased Appetite	2/619 (0.3%)		1/303 (0.3%)
Hyperglycaemia	2/619 (0.3%)		0/303 (0%)
Hyponatraemia	2/619 (0.3%)		0/303 (0%)
Hypercalcaemia	0/619 (0%)		1/303 (0.3%)
Hypoglycaemia	1/619 (0.2%)		0/303 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	2/619 (0.3%)		0/303 (0%)
Musculoskeletal Pain	2/619 (0.3%)		2/303 (0.7%)
Arthralgia	1/619 (0.2%)		0/303 (0%)
Bone Pain	1/619 (0.2%)		0/303 (0%)
Muscle Twitching	1/619 (0.2%)		1/303 (0.3%)
Musculoskeletal Chest Pain	1/619 (0.2%)		0/303 (0%)
Myalgia	1/619 (0.2%)		0/303 (0%)
Neck Pain	1/619 (0.2%)		0/303 (0%)
Osteoarthritis	0/619 (0%)		1/303 (0.3%)
Pain In Extremity	1/619 (0.2%)		1/303 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer Pain	1/619 (0.2%)		0/303 (0%)
Nervous system disorders
Convulsion	5/619 (0.8%)		1/303 (0.3%)
Cerebral Infarction	0/619 (0%)		3/303 (1%)
Cerebral Ischaemia	3/619 (0.5%)		0/303 (0%)
Cerebrovascular Accident	3/619 (0.5%)		1/303 (0.3%)
Cerebral Haemorrhage	1/619 (0.2%)		0/303 (0%)
Cognitive Disorder	1/619 (0.2%)		0/303 (0%)
Dizziness	1/619 (0.2%)		0/303 (0%)
Encephalitis	1/619 (0.2%)		0/303 (0%)
Loss Of Consciousness	0/619 (0%)		1/303 (0.3%)
Paraesthesia	1/619 (0.2%)		0/303 (0%)
Partial Seizures	1/619 (0.2%)		0/303 (0%)
Somnolence	1/619 (0.2%)		0/303 (0%)
Subarachnoid Haemorrhage	1/619 (0.2%)		0/303 (0%)
Syncope	0/619 (0%)		1/303 (0.3%)
Transient Ischaemic Attack	1/619 (0.2%)		0/303 (0%)
Tremor	1/619 (0.2%)		0/303 (0%)
Psychiatric disorders
Confusional State	0/619 (0%)		2/303 (0.7%)
Anxiety	1/619 (0.2%)		0/303 (0%)
Depression	1/619 (0.2%)		0/303 (0%)
Renal and urinary disorders
Urinary Retention	0/619 (0%)		2/303 (0.7%)
Calculus Urinary	0/619 (0%)		1/303 (0.3%)
Renal Failure	1/619 (0.2%)		0/303 (0%)
Renal Failure Acute	1/619 (0.2%)		0/303 (0%)
Urinary Incontinence	1/619 (0.2%)		0/303 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	12/619 (1.9%)		5/303 (1.7%)
Pleural Effusion	5/619 (0.8%)		5/303 (1.7%)
Pulmonary Embolism	3/619 (0.5%)		5/303 (1.7%)
Haemoptysis	3/619 (0.5%)		0/303 (0%)
Cough	2/619 (0.3%)		1/303 (0.3%)
Pneumonia Aspiration	2/619 (0.3%)		0/303 (0%)
Pneumonitis	2/619 (0.3%)		0/303 (0%)
Acute Respiratory Distress Syndrome	1/619 (0.2%)		0/303 (0%)
Bronchial Haemorrhage	1/619 (0.2%)		0/303 (0%)
Bronchospasm	1/619 (0.2%)		0/303 (0%)
Idiopathic Pulmonary Fibrosis	1/619 (0.2%)		0/303 (0%)
Pneumothorax	1/619 (0.2%)		0/303 (0%)
Pulmonary Artery Thrombosis	1/619 (0.2%)		0/303 (0%)
Pulmonary Haemorrhage	1/619 (0.2%)		1/303 (0.3%)
Respiratory Failure	1/619 (0.2%)		1/303 (0.3%)
Respiratory Tract Haemorrhage	1/619 (0.2%)		0/303 (0%)
Skin and subcutaneous tissue disorders
Rash	4/619 (0.6%)		0/303 (0%)
Stevens-Johnson Syndrome	3/619 (0.5%)		0/303 (0%)
Photosensitivity Reaction	2/619 (0.3%)		0/303 (0%)
Dermatitis Allergic	1/619 (0.2%)		0/303 (0%)
Dry Skin	1/619 (0.2%)		0/303 (0%)
Erythema	1/619 (0.2%)		0/303 (0%)
Erythema Multiforme	1/619 (0.2%)		0/303 (0%)
Rash Pruritic	1/619 (0.2%)		0/303 (0%)
Vascular disorders
Hypertension	7/619 (1.1%)		0/303 (0%)
Deep Vein Thrombosis	2/619 (0.3%)		0/303 (0%)
Arterial Thrombosis Limb	1/619 (0.2%)		0/303 (0%)
Hypotension	0/619 (0%)		1/303 (0.3%)
Jugular Vein Thrombosis	0/619 (0%)		1/303 (0.3%)
Thrombophlebitis Superficial	1/619 (0.2%)		0/303 (0%)
Visceral Arterial Ischaemia	0/619 (0%)		1/303 (0.3%)
Other (Not Including Serious) Adverse Events
	Vandetanib		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	557/619 (90%)		234/303 (77.2%)
Blood and lymphatic system disorders
Anaemia	19/619 (3.1%)		19/303 (6.3%)
Gastrointestinal disorders
Diarrhoea	284/619 (45.9%)		34/303 (11.2%)
Nausea	138/619 (22.3%)		51/303 (16.8%)
Constipation	88/619 (14.2%)		63/303 (20.8%)
Vomiting	82/619 (13.2%)		36/303 (11.9%)
Stomatitis	34/619 (5.5%)		13/303 (4.3%)
Abdominal Pain	26/619 (4.2%)		19/303 (6.3%)
General disorders
Fatigue	109/619 (17.6%)		50/303 (16.5%)
Asthenia	62/619 (10%)		30/303 (9.9%)
Pyrexia	44/619 (7.1%)		29/303 (9.6%)
Oedema Peripheral	33/619 (5.3%)		29/303 (9.6%)
Weight Decreased	47/619 (7.6%)		18/303 (5.9%)
Electrocardiogram Qt Prolonged	37/619 (6%)		1/303 (0.3%)
Metabolism and nutrition disorders
Decreased Appetite	143/619 (23.1%)		63/303 (20.8%)
Musculoskeletal and connective tissue disorders
Back Pain	54/619 (8.7%)		19/303 (6.3%)
Musculoskeletal Pain	22/619 (3.6%)		20/303 (6.6%)
Nervous system disorders
Dizziness	68/619 (11%)		27/303 (8.9%)
Headache	61/619 (9.9%)		24/303 (7.9%)
Psychiatric disorders
Insomnia	63/619 (10.2%)		24/303 (7.9%)
Renal and urinary disorders
Proteinuria	56/619 (9%)		10/303 (3.3%)
Respiratory, thoracic and mediastinal disorders
Cough	108/619 (17.4%)		53/303 (17.5%)
Dyspnoea	98/619 (15.8%)		52/303 (17.2%)
Skin and subcutaneous tissue disorders
Rash	258/619 (41.7%)		33/303 (10.9%)
Pruritus	70/619 (11.3%)		16/303 (5.3%)
Dry Skin	49/619 (7.9%)		8/303 (2.6%)
Vascular disorders
Hypertension	160/619 (25.8%)		9/303 (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.