ZACTIMA (an Anti-EGFR / Anti-VEGF Agent) Combined With Docetaxel Compared to Docetaxel in Non-small Cell Lung Cancer (ZODIAC)

• ClinicalTrials.gov Identifier: NCT00312377
• Recruitment Status: Completed
• First Posted: April 10, 2006
• Results First Posted: May 24, 2011
• Last Update Posted: September 30, 2016
• Sponsor: Genzyme, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Genzyme, a Sanofi Company )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Non-small Cell Lung Cancer; Lung Cancer
• Interventions: Drug: Docetaxel; Drug: Vandetanib
• Enrollment: 1690

Participant Flow

Recruitment Details	First patient enrolled 08 May 2006, last patient enrolled 14 March 2008, cut off date 22 August 2008
Pre-assignment Details

Arm/Group Title	Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel
Arm/Group Description	Vandetanib 100 mg oral tablet taken once daily in combination with docetaxel 75 mg/m2 IVb infusion every 21 days up to a maximum of 6 cycles	Placebo tablet taken once daily plus docetaxel 75 mg/m2 IVb infusion every 21 days up to a maximum of 6 cycles
Period Title: Overall Study
Started	694 [1]	697 [1]
Completed	50 [2]	29 [2]
Not Completed	644	668
Reason Not Completed
Death	403	418
Withdrawal by Subject	23	30
Lost to Follow-up	9	12
Non-compliance	0	2
Randomised but never received treatment	6	6
Discontinue treatment survival follow up	202	200
Site ended participation in study	1	0
[1] randomised patients; [2] ongoing study treatment at data cut-off

Baseline Characteristics

Arm/Group Title		Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel	Total
Arm/Group Description		Vandetanib 100 mg plus docetaxel	Placebo plus docetaxel	Total of all reporting groups
Overall Number of Baseline Participants		694	697	1391
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	694 participants	697 participants	1391 participants
		58.5; (28 to 82)	58.4; (20 to 82)	58.45; (20 to 82)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	694 participants	697 participants	1391 participants
	Female	497 71.6%	473 67.9%	970 69.7%
	Male	197 28.4%	224 32.1%	421 30.3%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS) in the Overall Population
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 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	RECIST tumour assessments carried out every 6 weeks from randomisation until the date of first documented objective disease progression or date of death from any cause, whichever came first assessed up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel
Arm/Group Description:	Vandetanib 100 mg plus docetaxel	Placebo plus docetaxel
Overall Number of Participants Analyzed	694	697
Median (95% Confidence Interval); Unit of Measure: Weeks
	17.3; (15 to 18)	14; (12.7 to 16.9)

2. Primary Outcome

Title	Progression-Free Survival (PFS) in the Female Population
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 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	RECIST tumour assessments carried out every 6 weeks from randomisation until the date of first documented objective disease progression or date of death from any cause, whichever came first assessed up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel
Arm/Group Description:	Vandetanib 100 mg plus docetaxel	Placebo plus docetaxel
Overall Number of Participants Analyzed	197	224
Median (95% Confidence Interval); Unit of Measure: Weeks
	20.1; (17.9 to 23.9)	18.3; (15 to 22.1)

3. Secondary Outcome

Title	Overall Survival (OS) in the Overall Population
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 100 mg Plus Docetaxel	Placebo Plus Docetaxel
Arm/Group Description:	Vandetanib 100 mg plus docetaxel	Placebo plus docetaxel
Overall Number of Participants Analyzed	694	697
Median (95% Confidence Interval); Unit of Measure: Months
	10.6; (9.6 to 11.5)	10; (9.2 to 10.8)

4. Secondary Outcome

Title	Overall Survival (OS) in the Female Population
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 100 mg Plus Docetaxel	Placebo Plus Docetaxel
Arm/Group Description:	Vandetanib 100 mg plus docetaxel	Placebo plus docetaxel
Overall Number of Participants Analyzed	197	224
Median (95% Confidence Interval); Unit of Measure: Months
	12.7; (10.5 to 17.1)	14.2; (10.8 to 16.2)

5. 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	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 6 weeks from randomisation until objective progression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel
Arm/Group Description:	Vandetanib 100 mg plus docetaxel	Placebo plus docetaxel
Overall Number of Participants Analyzed	694	697
Measure Type: Number; Unit of Measure: Participants
	120	71

6. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	Disease control rate is defined as the number of patients who achieved disease control at least 6 weeks following randomisation. Disease control at 6 weeks is defined as a best objective response of complete response (CR), partial response (PR) or stable disease (SD) >= 6 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 >= 6 is assigned to patients who have not responded and have no evidence of progression at least 6 weeks after randomisation.
Time Frame	RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel
Arm/Group Description:	Vandetanib 100 mg plus docetaxel	Placebo plus docetaxel
Overall Number of Participants Analyzed	694	697
Measure Type: Number; Unit of Measure: Participants
	413	380

7. 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 6 weeks from randomisation until objective progression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel
Arm/Group Description:	Vandetanib 100 mg plus docetaxel	Placebo plus docetaxel
Overall Number of Participants Analyzed	694	697
Median (Full Range); Unit of Measure: Weeks
	29.9; (7.14 to 72.29)	19.7; (9.71 to 41.86)

8. Secondary Outcome

Title	Time to Deterioration of Disease-related Symptoms (TDS) by Functional Assessment of Cancer Therapy - Lung (FACT-L) Lung Cancer Subscale (LCS).
Description	The lung cancer subscale (LCS) consists of 7 items of the FACT-L (3 items relating to breathing/dyspnea, and 1 item each relating to cough, weight loss, appetite, and cognition). The LCS total score is the sum of the scores from the 7 items. Time to deterioration is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 21 days. A patient will be 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 21 days.
Time Frame	FACT-L questionnaires are to be administered every 3 weeks after randomisation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel
Arm/Group Description:	Vandetanib 100 mg plus docetaxel	Placebo plus docetaxel
Overall Number of Participants Analyzed	694	697
Median (Inter-Quartile Range); Unit of Measure: Weeks
	15; (6.1 to 82.3)	11.9; (6.0 to 28.1)

9. Secondary Outcome

Title	Time to Deterioration of Disease-related Symptoms (TDS) by FACT-L Pulmonary Symptom Index (PSI)
Description	The pulmonary symptom index (PSI) consists of 4 items of the LCS relating to pulmonary symptoms (i.e. 3 items relating to breathing/dyspnea, and 1 item relating to cough). The PSI score is the sum of the scores from the 4 items. Time to deterioration is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 21 days. A patient will be 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 21 days.
Time Frame	FACT-L questionnaires are to be administered every 3 weeks after randomisation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel
Arm/Group Description:	Vandetanib 100 mg plus docetaxel	Placebo plus docetaxel
Overall Number of Participants Analyzed	694	697
Median (Inter-Quartile Range); Unit of Measure: Weeks
	12.3; (5.9 to 36.7)	11.9; (6 to 28.4)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel
Arm/Group Description	Vandetanib 100 mg plus docetaxel	Placebo plus docetaxel
All-Cause Mortality
	Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel
	Affected / at Risk (%)	Affected / at Risk (%)
Total	263/694 (37.90%)	232/697 (33.29%)
Blood and lymphatic system disorders
Febrile Neutropenia † 1	46/694 (6.63%)	38/697 (5.45%)
Neutropenia † 1	16/694 (2.31%)	18/697 (2.58%)
Anaemia † 1	4/694 (0.58%)	6/697 (0.86%)
Leukopenia † 1	3/694 (0.43%)	2/697 (0.29%)
Leukocytosis † 1	0/694 (0.00%)	2/697 (0.29%)
Bone Marrow Failure † 1	1/694 (0.14%)	0/697 (0.00%)
Febrile Bone Marrow Aplasia † 1	1/694 (0.14%)	0/697 (0.00%)
Iron Deficiency Anaemia † 1	1/694 (0.14%)	0/697 (0.00%)
Thrombocytopenia † 1	1/694 (0.14%)	1/697 (0.14%)
Cardiac disorders
Atrial Fibrillation † 1	3/694 (0.43%)	10/697 (1.43%)
Myocardial Infarction † 1	0/694 (0.00%)	4/697 (0.57%)
Cardiac Arrest † 1	1/694 (0.14%)	3/697 (0.43%)
Cardiac Failure † 1	0/694 (0.00%)	3/697 (0.43%)
Acute Myocardial Infarction † 1	2/694 (0.29%)	2/697 (0.29%)
Atrial Flutter † 1	2/694 (0.29%)	1/697 (0.14%)
Angina Unstable † 1	1/694 (0.14%)	0/697 (0.00%)
Arrhythmia † 1	0/694 (0.00%)	1/697 (0.14%)
Atrioventricular Block Complete † 1	1/694 (0.14%)	0/697 (0.00%)
Atrioventricular Block Second Degree † 1	0/694 (0.00%)	1/697 (0.14%)
Cardiac Tamponade † 1	0/694 (0.00%)	1/697 (0.14%)
Cardio-Respiratory Arrest † 1	1/694 (0.14%)	0/697 (0.00%)
Extrasystoles † 1	1/694 (0.14%)	0/697 (0.00%)
Pericardial Effusion † 1	1/694 (0.14%)	0/697 (0.00%)
Pericarditis † 1	0/694 (0.00%)	1/697 (0.14%)
Supraventricular Tachycardia † 1	1/694 (0.14%)	0/697 (0.00%)
Tachyarrhythmia † 1	0/694 (0.00%)	1/697 (0.14%)
Tachycardia † 1	1/694 (0.14%)	0/697 (0.00%)
Ventricular Extrasystoles † 1	0/694 (0.00%)	1/697 (0.14%)
Congenital, familial and genetic disorders
Hereditary Angioedema † 1	1/694 (0.14%)	0/697 (0.00%)
Ear and labyrinth disorders
Deafness Unilateral † 1	1/694 (0.14%)	0/697 (0.00%)
Vertigo † 1	1/694 (0.14%)	0/697 (0.00%)
Eye disorders
Ocular Surface Disease † 1	1/694 (0.14%)	0/697 (0.00%)
Retinal Artery Occlusion † 1	1/694 (0.14%)	0/697 (0.00%)
Gastrointestinal disorders
Diarrhoea † 1	14/694 (2.02%)	11/697 (1.58%)
Vomiting † 1	7/694 (1.01%)	8/697 (1.15%)
Nausea † 1	5/694 (0.72%)	4/697 (0.57%)
Abdominal Pain Upper † 1	4/694 (0.58%)	1/697 (0.14%)
Constipation † 1	0/694 (0.00%)	3/697 (0.43%)
Gastric Ulcer † 1	0/694 (0.00%)	3/697 (0.43%)
Abdominal Pain † 1	2/694 (0.29%)	1/697 (0.14%)
Gastrointestinal Haemorrhage † 1	1/694 (0.14%)	2/697 (0.29%)
Stomatitis † 1	2/694 (0.29%)	0/697 (0.00%)
Appendicitis Perforated † 1	1/694 (0.14%)	0/697 (0.00%)
Ascites † 1	0/694 (0.00%)	1/697 (0.14%)
Dyspepsia † 1	0/694 (0.00%)	1/697 (0.14%)
Dysphagia † 1	1/694 (0.14%)	1/697 (0.14%)
Enteritis † 1	1/694 (0.14%)	0/697 (0.00%)
Enterocolitis † 1	1/694 (0.14%)	0/697 (0.00%)
Gastric Haemorrhage † 1	0/694 (0.00%)	1/697 (0.14%)
Gastritis † 1	0/694 (0.00%)	1/697 (0.14%)
Gastrointestinal Inflammation † 1	1/694 (0.14%)	0/697 (0.00%)
Haematochezia † 1	1/694 (0.14%)	0/697 (0.00%)
Ileus Paralytic † 1	1/694 (0.14%)	0/697 (0.00%)
Inguinal Hernia † 1	1/694 (0.14%)	0/697 (0.00%)
Intestinal Obstruction † 1	1/694 (0.14%)	0/697 (0.00%)
Lower Gastrointestinal Haemorrhage † 1	1/694 (0.14%)	0/697 (0.00%)
Oesophageal Fistula † 1	1/694 (0.14%)	0/697 (0.00%)
Oesophageal Stenosis † 1	1/694 (0.14%)	0/697 (0.00%)
Proctitis Haemorrhagic † 1	0/694 (0.00%)	1/697 (0.14%)
Upper Gastrointestinal Haemorrhage † 1	0/694 (0.00%)	1/697 (0.14%)
General disorders
Pyrexia † 1	13/694 (1.87%)	12/697 (1.72%)
Asthenia † 1	2/694 (0.29%)	5/697 (0.72%)
Chest Pain † 1	3/694 (0.43%)	0/697 (0.00%)
Malaise † 1	3/694 (0.43%)	0/697 (0.00%)
Performance Status Decreased † 1	3/694 (0.43%)	0/697 (0.00%)
Fatigue † 1	1/694 (0.14%)	2/697 (0.29%)
General Physical Health Deterioration † 1	1/694 (0.14%)	2/697 (0.29%)
Mucosal Inflammation † 1	1/694 (0.14%)	2/697 (0.29%)
Chills † 1	1/694 (0.14%)	0/697 (0.00%)
Death † 1	0/694 (0.00%)	1/697 (0.14%)
Multi-Organ Failure † 1	1/694 (0.14%)	1/697 (0.14%)
Pain † 1	1/694 (0.14%)	0/697 (0.00%)
Sudden Death † 1	1/694 (0.14%)	1/697 (0.14%)
Systemic Inflammatory Response Syndrome † 1	0/694 (0.00%)	1/697 (0.14%)
Immune system disorders
Anaphylactic Shock † 1	1/694 (0.14%)	2/697 (0.29%)
Drug Hypersensitivity † 1	2/694 (0.29%)	1/697 (0.14%)
Infections and infestations
Pneumonia † 1	33/694 (4.76%)	26/697 (3.73%)
Respiratory Tract Infection † 1	5/694 (0.72%)	6/697 (0.86%)
Sepsis † 1	5/694 (0.72%)	5/697 (0.72%)
Upper Respiratory Tract Infection † 1	0/694 (0.00%)	5/697 (0.72%)
Gastroenteritis † 1	4/694 (0.58%)	3/697 (0.43%)
Lung Infection † 1	4/694 (0.58%)	2/697 (0.29%)
Urinary Tract Infection † 1	4/694 (0.58%)	3/697 (0.43%)
Lower Respiratory Tract Infection † 1	3/694 (0.43%)	1/697 (0.14%)
Septic Shock † 1	3/694 (0.43%)	1/697 (0.14%)
Bacterial Infection † 1	2/694 (0.29%)	0/697 (0.00%)
Bronchitis † 1	0/694 (0.00%)	2/697 (0.29%)
Bronchopneumonia † 1	0/694 (0.00%)	2/697 (0.29%)
Infection † 1	0/694 (0.00%)	2/697 (0.29%)
Neutropenic Infection † 1	1/694 (0.14%)	2/697 (0.29%)
Urosepsis † 1	2/694 (0.29%)	0/697 (0.00%)
Appendicitis † 1	1/694 (0.14%)	0/697 (0.00%)
Bacteraemia † 1	1/694 (0.14%)	0/697 (0.00%)
Bacterial Sepsis † 1	1/694 (0.14%)	0/697 (0.00%)
Bronchopulmonary Aspergillosis † 1	1/694 (0.14%)	0/697 (0.00%)
Catheter Related Infection † 1	0/694 (0.00%)	1/697 (0.14%)
Cellulitis † 1	1/694 (0.14%)	0/697 (0.00%)
Central Line Infection † 1	0/694 (0.00%)	1/697 (0.14%)
Diverticulitis † 1	1/694 (0.14%)	1/697 (0.14%)
Empyema † 1	1/694 (0.14%)	0/697 (0.00%)
Epiglottitis † 1	0/694 (0.00%)	1/697 (0.14%)
Gastrointestinal Infection † 1	1/694 (0.14%)	0/697 (0.00%)
Infective Exacerbation Of Chronic Obstructive Airways Disease † 1	0/694 (0.00%)	1/697 (0.14%)
Infective Myositis † 1	1/694 (0.14%)	0/697 (0.00%)
Lobar Pneumonia † 1	1/694 (0.14%)	0/697 (0.00%)
Lung Abscess † 1	1/694 (0.14%)	1/697 (0.14%)
Oesophageal Candidiasis † 1	1/694 (0.14%)	0/697 (0.00%)
Perianal Abscess † 1	0/694 (0.00%)	1/697 (0.14%)
Pneumocystis Jiroveci Pneumonia † 1	1/694 (0.14%)	0/697 (0.00%)
Pneumonia Streptococcal † 1	0/694 (0.00%)	1/697 (0.14%)
Pyothorax † 1	1/694 (0.14%)	0/697 (0.00%)
Rash Pustular † 1	1/694 (0.14%)	0/697 (0.00%)
Rectal Abscess † 1	1/694 (0.14%)	0/697 (0.00%)
Respiratory Tract Infection Bacterial † 1	0/694 (0.00%)	1/697 (0.14%)
Skin Bacterial Infection † 1	1/694 (0.14%)	0/697 (0.00%)
Staphylococcal Infection † 1	1/694 (0.14%)	0/697 (0.00%)
Tuberculosis † 1	1/694 (0.14%)	0/697 (0.00%)
Injury, poisoning and procedural complications
Femur Fracture † 1	2/694 (0.29%)	1/697 (0.14%)
Humerus Fracture † 1	0/694 (0.00%)	2/697 (0.29%)
Brain Contusion † 1	0/694 (0.00%)	1/697 (0.14%)
Facial Bones Fracture † 1	0/694 (0.00%)	1/697 (0.14%)
Foot Fracture † 1	1/694 (0.14%)	0/697 (0.00%)
Hip Fracture † 1	1/694 (0.14%)	0/697 (0.00%)
Lower Limb Fracture † 1	1/694 (0.14%)	0/697 (0.00%)
Multiple Fractures † 1	0/694 (0.00%)	1/697 (0.14%)
Radiation Pneumonitis † 1	1/694 (0.14%)	0/697 (0.00%)
Skin Laceration † 1	0/694 (0.00%)	1/697 (0.14%)
Skull Fracture † 1	0/694 (0.00%)	1/697 (0.14%)
Weight Decreased † 1	0/694 (0.00%)	2/697 (0.29%)
White Blood Cell Count Decreased † 1	0/694 (0.00%)	2/697 (0.29%)
Alanine Aminotransferase Increased † 1	0/694 (0.00%)	1/697 (0.14%)
Aspartate Aminotransferase Increased † 1	0/694 (0.00%)	1/697 (0.14%)
Blood Alkaline Phosphatase Increased † 1	0/694 (0.00%)	1/697 (0.14%)
Blood Pressure Orthostatic Decreased † 1	1/694 (0.14%)	0/697 (0.00%)
Electrocardiogram T Wave Abnormal † 1	1/694 (0.14%)	0/697 (0.00%)
Neutrophil Count Decreased † 1	0/694 (0.00%)	1/697 (0.14%)
Metabolism and nutrition disorders
Anorexia † 1	3/694 (0.43%)	2/697 (0.29%)
Dehydration † 1	1/694 (0.14%)	3/697 (0.43%)
Hyperkalaemia † 1	1/694 (0.14%)	2/697 (0.29%)
Hypoglycaemia † 1	2/694 (0.29%)	2/697 (0.29%)
Hyponatraemia † 1	1/694 (0.14%)	2/697 (0.29%)
Diabetes Mellitus † 1	1/694 (0.14%)	0/697 (0.00%)
Failure To Thrive † 1	1/694 (0.14%)	0/697 (0.00%)
Hypercalcaemia † 1	1/694 (0.14%)	1/697 (0.14%)
Hyperglycaemia † 1	1/694 (0.14%)	1/697 (0.14%)
Hypokalaemia † 1	1/694 (0.14%)	0/697 (0.00%)
Type 2 Diabetes Mellitus † 1	0/694 (0.00%)	1/697 (0.14%)
Musculoskeletal and connective tissue disorders
Back Pain † 1	2/694 (0.29%)	4/697 (0.57%)
Musculoskeletal Chest Pain † 1	3/694 (0.43%)	4/697 (0.57%)
Arthralgia † 1	0/694 (0.00%)	1/697 (0.14%)
Bone Pain † 1	1/694 (0.14%)	1/697 (0.14%)
Flank Pain † 1	0/694 (0.00%)	1/697 (0.14%)
Muscular Weakness † 1	1/694 (0.14%)	1/697 (0.14%)
Musculoskeletal Pain † 1	0/694 (0.00%)	1/697 (0.14%)
Myalgia † 1	0/694 (0.00%)	1/697 (0.14%)
Pain In Extremity † 1	1/694 (0.14%)	1/697 (0.14%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour Pain † 1	2/694 (0.29%)	2/697 (0.29%)
Metastatic Pain † 1	1/694 (0.14%)	0/697 (0.00%)
Myelodysplastic Syndrome † 1	1/694 (0.14%)	0/697 (0.00%)
Nervous system disorders
Convulsion † 1	4/694 (0.58%)	1/697 (0.14%)
Dizziness † 1	3/694 (0.43%)	4/697 (0.57%)
Headache † 1	1/694 (0.14%)	3/697 (0.43%)
Loss Of Consciousness † 1	3/694 (0.43%)	1/697 (0.14%)
Somnolence † 1	0/694 (0.00%)	2/697 (0.29%)
Syncope † 1	2/694 (0.29%)	2/697 (0.29%)
Altered State Of Consciousness † 1	1/694 (0.14%)	0/697 (0.00%)
Ataxia † 1	0/694 (0.00%)	1/697 (0.14%)
Brachial Plexopathy † 1	0/694 (0.00%)	1/697 (0.14%)
Cauda Equina Syndrome † 1	0/694 (0.00%)	1/697 (0.14%)
Cerebral Haemorrhage † 1	0/694 (0.00%)	1/697 (0.14%)
Cerebral Infarction † 1	1/694 (0.14%)	0/697 (0.00%)
Cerebral Ischaemia † 1	1/694 (0.14%)	1/697 (0.14%)
Cerebrovascular Accident † 1	1/694 (0.14%)	1/697 (0.14%)
Coma † 1	0/694 (0.00%)	1/697 (0.14%)
Coma Hepatic † 1	0/694 (0.00%)	1/697 (0.14%)
Dyskinesia † 1	0/694 (0.00%)	1/697 (0.14%)
Hemiparesis † 1	1/694 (0.14%)	0/697 (0.00%)
Ischaemic Stroke † 1	1/694 (0.14%)	0/697 (0.00%)
Paraplegia † 1	0/694 (0.00%)	1/697 (0.14%)
Peripheral Sensory Neuropathy † 1	1/694 (0.14%)	0/697 (0.00%)
Polyneuropathy † 1	1/694 (0.14%)	0/697 (0.00%)
Pyramidal Tract Syndrome † 1	0/694 (0.00%)	1/697 (0.14%)
Spinal Cord Compression † 1	1/694 (0.14%)	0/697 (0.00%)
Subarachnoid Haemorrhage † 1	0/694 (0.00%)	1/697 (0.14%)
Psychiatric disorders
Mental Status Changes † 1	2/694 (0.29%)	1/697 (0.14%)
Anxiety † 1	0/694 (0.00%)	1/697 (0.14%)
Confusional State † 1	1/694 (0.14%)	0/697 (0.00%)
Delirium † 1	0/694 (0.00%)	1/697 (0.14%)
Psychotic Behaviour † 1	1/694 (0.14%)	0/697 (0.00%)
Suicidal Ideation † 1	0/694 (0.00%)	1/697 (0.14%)
Renal and urinary disorders
Dysuria † 1	0/694 (0.00%)	2/697 (0.29%)
Renal Failure † 1	2/694 (0.29%)	1/697 (0.14%)
Haematuria † 1	1/694 (0.14%)	0/697 (0.00%)
Nephrolithiasis † 1	0/694 (0.00%)	1/697 (0.14%)
Renal Failure Acute † 1	1/694 (0.14%)	0/697 (0.00%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	22/694 (3.17%)	21/697 (3.01%)
Interstitial Lung Disease † 1	12/694 (1.73%)	6/697 (0.86%)
Pulmonary Embolism † 1	2/694 (0.29%)	8/697 (1.15%)
Haemoptysis † 1	5/694 (0.72%)	6/697 (0.86%)
Respiratory Failure † 1	5/694 (0.72%)	6/697 (0.86%)
Pneumonitis † 1	4/694 (0.58%)	5/697 (0.72%)
Pneumothorax † 1	1/694 (0.14%)	5/697 (0.72%)
Pleural Effusion † 1	4/694 (0.58%)	3/697 (0.43%)
Chronic Obstructive Pulmonary Disease † 1	0/694 (0.00%)	3/697 (0.43%)
Cough † 1	3/694 (0.43%)	0/697 (0.00%)
Aspiration † 1	2/694 (0.29%)	0/697 (0.00%)
Epistaxis † 1	0/694 (0.00%)	2/697 (0.29%)
Hypoxia † 1	2/694 (0.29%)	1/697 (0.14%)
Pulmonary Haemorrhage † 1	1/694 (0.14%)	2/697 (0.29%)
Respiratory Distress † 1	1/694 (0.14%)	2/697 (0.29%)
Acute Respiratory Distress Syndrome † 1	1/694 (0.14%)	0/697 (0.00%)
Asthma † 1	0/694 (0.00%)	1/697 (0.14%)
Bronchospasm † 1	1/694 (0.14%)	0/697 (0.00%)
Cryptogenic Organising Pneumonia † 1	1/694 (0.14%)	0/697 (0.00%)
Diaphragmatic Rupture † 1	0/694 (0.00%)	1/697 (0.14%)
Dyspnoea Exertional † 1	0/694 (0.00%)	1/697 (0.14%)
Hydropneumothorax † 1	1/694 (0.14%)	0/697 (0.00%)
Laryngeal Inflammation † 1	1/694 (0.14%)	0/697 (0.00%)
Lung Infiltration † 1	0/694 (0.00%)	1/697 (0.14%)
Pleurisy † 1	0/694 (0.00%)	1/697 (0.14%)
Pneumonia Aspiration † 1	1/694 (0.14%)	0/697 (0.00%)
Productive Cough † 1	0/694 (0.00%)	1/697 (0.14%)
Pulmonary Alveolar Haemorrhage † 1	0/694 (0.00%)	1/697 (0.14%)
Pulmonary Oedema † 1	0/694 (0.00%)	1/697 (0.14%)
Respiratory Depression † 1	1/694 (0.14%)	0/697 (0.00%)
Skin and subcutaneous tissue disorders
Rash † 1	15/694 (2.16%)	1/697 (0.14%)
Photosensitivity Reaction † 1	5/694 (0.72%)	0/697 (0.00%)
Toxic Epidermal Necrolysis † 1	4/694 (0.58%)	0/697 (0.00%)
Dermatitis Exfoliative † 1	3/694 (0.43%)	0/697 (0.00%)
Stevens-Johnson Syndrome † 1	3/694 (0.43%)	0/697 (0.00%)
Drug Eruption † 1	2/694 (0.29%)	0/697 (0.00%)
Erythema † 1	2/694 (0.29%)	0/697 (0.00%)
Pruritus † 1	2/694 (0.29%)	0/697 (0.00%)
Rash Erythematous † 1	2/694 (0.29%)	0/697 (0.00%)
Toxic Skin Eruption † 1	2/694 (0.29%)	0/697 (0.00%)
Dermatitis † 1	1/694 (0.14%)	0/697 (0.00%)
Erythema Multiforme † 1	1/694 (0.14%)	0/697 (0.00%)
Exfoliative Rash † 1	1/694 (0.14%)	0/697 (0.00%)
Palmar-Plantar Erythrodysaesthesia Syndrome † 1	1/694 (0.14%)	0/697 (0.00%)
Rash Maculo-Papular † 1	1/694 (0.14%)	0/697 (0.00%)
Skin Toxicity † 1	1/694 (0.14%)	0/697 (0.00%)
Telangiectasia † 1	1/694 (0.14%)	0/697 (0.00%)
Vascular disorders
Deep Vein Thrombosis † 1	1/694 (0.14%)	6/697 (0.86%)
Hypotension † 1	5/694 (0.72%)	1/697 (0.14%)
Peripheral Arterial Occlusive Disease † 1	1/694 (0.14%)	0/697 (0.00%)
Peripheral Ischaemia † 1	1/694 (0.14%)	0/697 (0.00%)
Shock † 1	0/694 (0.00%)	1/697 (0.14%)
Subclavian Vein Thrombosis † 1	1/694 (0.14%)	0/697 (0.00%)
Superior Vena Caval Stenosis † 1	1/694 (0.14%)	0/697 (0.00%)
Vasculitis † 1	0/694 (0.00%)	1/697 (0.14%)
Vena Cava Thrombosis † 1	0/694 (0.00%)	1/697 (0.14%)
Venous Thrombosis † 1	1/694 (0.14%)	0/697 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 11.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel
	Affected / at Risk (%)	Affected / at Risk (%)
Total	637/694 (91.79%)	630/697 (90.39%)
Blood and lymphatic system disorders
Neutropenia † 1	212/694 (30.55%)	174/697 (24.96%)
Leukopenia † 1	125/694 (18.01%)	106/697 (15.21%)
Anaemia † 1	68/694 (9.80%)	98/697 (14.06%)
Gastrointestinal disorders
Diarrhoea † 1	284/694 (40.92%)	218/697 (31.28%)
Nausea † 1	158/694 (22.77%)	221/697 (31.71%)
Vomiting † 1	105/694 (15.13%)	141/697 (20.23%)
Constipation † 1	119/694 (17.15%)	140/697 (20.09%)
Stomatitis † 1	80/694 (11.53%)	80/697 (11.48%)
Abdominal Pain † 1	41/694 (5.91%)	50/697 (7.17%)
Dyspepsia † 1	37/694 (5.33%)	25/697 (3.59%)
Abdominal Pain Upper † 1	30/694 (4.32%)	36/697 (5.16%)
General disorders
Fatigue † 1	208/694 (29.97%)	214/697 (30.70%)
Pyrexia † 1	127/694 (18.30%)	110/697 (15.78%)
Asthenia † 1	105/694 (15.13%)	90/697 (12.91%)
Oedema Peripheral † 1	49/694 (7.06%)	57/697 (8.18%)
Mucosal Inflammation † 1	49/694 (7.06%)	38/697 (5.45%)
Infections and infestations
Nasopharyngitis † 1	41/694 (5.91%)	37/697 (5.31%)
Weight Decreased † 1	54/694 (7.78%)	41/697 (5.88%)
Metabolism and nutrition disorders
Anorexia † 1	199/694 (28.67%)	204/697 (29.27%)
Musculoskeletal and connective tissue disorders
Myalgia † 1	90/694 (12.97%)	78/697 (11.19%)
Back Pain † 1	51/694 (7.35%)	62/697 (8.90%)
Arthralgia † 1	61/694 (8.79%)	52/697 (7.46%)
Pain In Extremity † 1	39/694 (5.62%)	31/697 (4.45%)
Musculoskeletal Pain † 1	35/694 (5.04%)	30/697 (4.30%)
Nervous system disorders
Headache † 1	58/694 (8.36%)	62/697 (8.90%)
Dizziness † 1	43/694 (6.20%)	58/697 (8.32%)
Dysgeusia † 1	40/694 (5.76%)	49/697 (7.03%)
Peripheral Sensory Neuropathy † 1	42/694 (6.05%)	48/697 (6.89%)
Paraesthesia † 1	42/694 (6.05%)	42/697 (6.03%)
Psychiatric disorders
Insomnia † 1	95/694 (13.69%)	73/697 (10.47%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	130/694 (18.73%)	133/697 (19.08%)
Dyspnoea † 1	102/694 (14.70%)	122/697 (17.50%)
Epistaxis † 1	50/694 (7.20%)	27/697 (3.87%)
Haemoptysis † 1	37/694 (5.33%)	45/697 (6.46%)
Dysphonia † 1	41/694 (5.91%)	20/697 (2.87%)
Hiccups † 1	30/694 (4.32%)	41/697 (5.88%)
Skin and subcutaneous tissue disorders
Rash † 1	282/694 (40.63%)	166/697 (23.82%)
Alopecia † 1	230/694 (33.14%)	240/697 (34.43%)
Pruritus † 1	65/694 (9.37%)	42/697 (6.03%)
Nail Disorder † 1	52/694 (7.49%)	46/697 (6.60%)
Dry Skin † 1	45/694 (6.48%)	30/697 (4.30%)
Photosensitivity Reaction † 1	42/694 (6.05%)	1/697 (0.14%)
Vascular disorders
Hypertension † 1	41/694 (5.91%)	13/697 (1.87%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 11.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Trial Transparency Team
• Organization: Sanofi
• EMail: Contact-US@sanofi.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lombard A, Mistry H, Aarons L, Ogungbenro K. Dose individualisation in oncology using chemotherapy-induced neutropenia: Example of docetaxel in non-small cell lung cancer patients. Br J Clin Pharmacol. 2021 Apr;87(4):2053-2063. doi: 10.1111/bcp.14614. Epub 2020 Dec 19.

Platt A, Morten J, Ji Q, Elvin P, Womack C, Su X, Donald E, Gray N, Read J, Bigley G, Blockley L, Cresswell C, Dale A, Davies A, Zhang T, Fan S, Fu H, Gladwin A, Harrod G, Stevens J, Williams V, Ye Q, Zheng L, de Boer R, Herbst RS, Lee JS, Vasselli J. A retrospective analysis of RET translocation, gene copy number gain and expression in NSCLC patients treated with vandetanib in four randomized Phase III studies. BMC Cancer. 2015 Mar 23;15:171. doi: 10.1186/s12885-015-1146-8.

Heymach JV, Lockwood SJ, Herbst RS, Johnson BE, Ryan AJ. EGFR biomarkers predict benefit from vandetanib in combination with docetaxel in a randomized phase III study of second-line treatment of patients with advanced non-small cell lung cancer. Ann Oncol. 2014 Oct;25(10):1941-1948. doi: 10.1093/annonc/mdu269. Epub 2014 Jul 23.

Herbst RS, Sun Y, Eberhardt WE, Germonpre P, Saijo N, Zhou C, Wang J, Li L, Kabbinavar F, Ichinose Y, Qin S, Zhang L, Biesma B, Heymach JV, Langmuir P, Kennedy SJ, Tada H, Johnson BE. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. Lancet Oncol. 2010 Jul;11(7):619-26. doi: 10.1016/S1470-2045(10)70132-7.

• Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
• ClinicalTrials.gov Identifier: NCT00312377
• Other Study ID Numbers: D4200C00032; 6474IL/0032; 2005-004749-32 ( EudraCT Number )
• First Submitted: April 6, 2006
• First Posted: April 10, 2006
• Results First Submitted: April 27, 2011
• Results First Posted: May 24, 2011
• Last Update Posted: September 30, 2016