Trial Outcomes & Findings for A Phase II, Double Blind Study of 2 Doses of ZACTIMA™(ZD6474) in Combination With FOLFIRI vs FOLFIRI Alone for the Treatment of Colorectal Cancer in Patients (NCT NCT00454116)
NCT ID: NCT00454116
Last Updated: 2016-10-07
Results Overview
Number of patients with objective disease progression or death (by any cause in the absence of objective progression)
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
106 participants
Primary outcome timeframe
Tumour assessments carried out at screening and then as per site clinical practice until objective progression. The only additional mandatory tumour assessment visit is at the point of data cut-off (28 March 2008 +/-3 days)
Results posted on
2016-10-07
Participant Flow
First patient randomised 14 March 2007, last patient randomised 21 Jan 2008, data cut off data 31 March 2008
Participant milestones
| Measure |
Vandetanib 100 mg Plus FOLFIRI
vandetanib 100 mg plus FOLFIRI
|
Vandetanib 300 mg Plus FOLFIRI
vandetanib 300 mg plus FOLFIRI
|
Placebo Plus FOLFIRI
placebo plus FOLFIRI
|
|---|---|---|---|
|
Overall Study
STARTED
|
35
|
36
|
35
|
|
Overall Study
COMPLETED
|
8
|
7
|
7
|
|
Overall Study
NOT COMPLETED
|
27
|
29
|
28
|
Reasons for withdrawal
| Measure |
Vandetanib 100 mg Plus FOLFIRI
vandetanib 100 mg plus FOLFIRI
|
Vandetanib 300 mg Plus FOLFIRI
vandetanib 300 mg plus FOLFIRI
|
Placebo Plus FOLFIRI
placebo plus FOLFIRI
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
5
|
11
|
9
|
|
Overall Study
Condition under investigation worsened
|
17
|
13
|
18
|
|
Overall Study
Withdrawal by Subject
|
3
|
3
|
1
|
|
Overall Study
Other
|
2
|
2
|
0
|
Baseline Characteristics
A Phase II, Double Blind Study of 2 Doses of ZACTIMA™(ZD6474) in Combination With FOLFIRI vs FOLFIRI Alone for the Treatment of Colorectal Cancer in Patients
Baseline characteristics by cohort
| Measure |
Vandetanib 100 mg Plus FOLFIRI
n=35 Participants
vandetanib 100 mg plus FOLFIRI
|
Vandetanib 300 mg Plus FOLFIRI
n=36 Participants
vandetanib 300 mg plus FOLFIRI
|
Placebo Plus FOLFIRI
n=35 Participants
placebo plus FOLFIRI
|
Total
n=106 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
57 years
n=5 Participants
|
57 years
n=7 Participants
|
59 years
n=5 Participants
|
58 years
n=4 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
43 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
63 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Tumour assessments carried out at screening and then as per site clinical practice until objective progression. The only additional mandatory tumour assessment visit is at the point of data cut-off (28 March 2008 +/-3 days)Number of patients with objective disease progression or death (by any cause in the absence of objective progression)
Outcome measures
| Measure |
Vandetanib 100 mg Plus FOLFIRI
n=35 Participants
vandetanib 100 mg plus FOLFIRI
|
Vandetanib 300 mg Plus FOLFIRI
n=36 Participants
vandetanib 300 mg plus FOLFIRI
|
Placebo Plus FOLFIRI
n=35 Participants
placebo plus FOLFIRI
|
|---|---|---|---|
|
Number of Patients With an Objective Disease Progression Event
|
20 Participants
|
24 Participants
|
24 Participants
|
Adverse Events
Vandetanib 100 mg Plus FOLFIRI
Serious events: 8 serious events
Other events: 32 other events
Deaths: 0 deaths
Vandetanib 300 mg Plus FOLFIRI
Serious events: 13 serious events
Other events: 36 other events
Deaths: 0 deaths
Placebo Plus FOLFIRI
Serious events: 12 serious events
Other events: 34 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Vandetanib 100 mg Plus FOLFIRI
n=35 participants at risk
vandetanib 100 mg plus FOLFIRI
|
Vandetanib 300 mg Plus FOLFIRI
n=36 participants at risk
vandetanib 300 mg plus FOLFIRI
|
Placebo Plus FOLFIRI
n=35 participants at risk
placebo plus FOLFIRI
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
|
0.00%
0/35
|
2.8%
1/36
|
0.00%
0/35
|
|
Skin and subcutaneous tissue disorders
PHOTOSENSITIVITY REACTION
|
2.9%
1/35
|
0.00%
0/36
|
0.00%
0/35
|
|
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA
|
0.00%
0/35
|
5.6%
2/36
|
0.00%
0/35
|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
0.00%
0/35
|
0.00%
0/36
|
5.7%
2/35
|
|
Cardiac disorders
ANGINA PECTORIS
|
2.9%
1/35
|
2.8%
1/36
|
0.00%
0/35
|
|
Cardiac disorders
PERICARDIAL EFFUSION
|
0.00%
0/35
|
0.00%
0/36
|
2.9%
1/35
|
|
Gastrointestinal disorders
DIARRHOEA
|
0.00%
0/35
|
8.3%
3/36
|
5.7%
2/35
|
|
Gastrointestinal disorders
GASTROINTESTINAL HAEMORRHAGE
|
0.00%
0/35
|
0.00%
0/36
|
5.7%
2/35
|
|
Gastrointestinal disorders
ILEUS
|
2.9%
1/35
|
0.00%
0/36
|
0.00%
0/35
|
|
Gastrointestinal disorders
INTESTINAL OBSTRUCTION
|
0.00%
0/35
|
0.00%
0/36
|
2.9%
1/35
|
|
Gastrointestinal disorders
PROCTITIS
|
2.9%
1/35
|
0.00%
0/36
|
0.00%
0/35
|
|
Gastrointestinal disorders
RECTAL HAEMORRHAGE
|
0.00%
0/35
|
2.8%
1/36
|
0.00%
0/35
|
|
General disorders
PYREXIA
|
2.9%
1/35
|
8.3%
3/36
|
8.6%
3/35
|
|
General disorders
CHEST PAIN
|
2.9%
1/35
|
0.00%
0/36
|
0.00%
0/35
|
|
Infections and infestations
CENTRAL LINE INFECTION
|
2.9%
1/35
|
5.6%
2/36
|
0.00%
0/35
|
|
Infections and infestations
BETA HAEMOLYTIC STREPTOCOCCAL INFECTION
|
0.00%
0/35
|
2.8%
1/36
|
0.00%
0/35
|
|
Infections and infestations
CELLULITIS
|
2.9%
1/35
|
0.00%
0/36
|
0.00%
0/35
|
|
Infections and infestations
EPSTEIN-BARR VIRUS INFECTION
|
0.00%
0/35
|
2.8%
1/36
|
0.00%
0/35
|
|
Infections and infestations
PNEUMONIA
|
0.00%
0/35
|
2.8%
1/36
|
2.9%
1/35
|
|
Infections and infestations
SEPSIS
|
0.00%
0/35
|
0.00%
0/36
|
2.9%
1/35
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
0.00%
0/35
|
2.8%
1/36
|
0.00%
0/35
|
|
Infections and infestations
URINARY TRACT INFECTION
|
0.00%
0/35
|
0.00%
0/36
|
2.9%
1/35
|
|
Infections and infestations
VIRAL INFECTION
|
0.00%
0/35
|
2.8%
1/36
|
0.00%
0/35
|
|
Metabolism and nutrition disorders
HYPERGLYCAEMIA
|
0.00%
0/35
|
0.00%
0/36
|
2.9%
1/35
|
|
Metabolism and nutrition disorders
HYPOKALAEMIA
|
0.00%
0/35
|
2.8%
1/36
|
0.00%
0/35
|
|
Metabolism and nutrition disorders
HYPONATRAEMIA
|
0.00%
0/35
|
2.8%
1/36
|
0.00%
0/35
|
|
Renal and urinary disorders
RENAL FAILURE
|
0.00%
0/35
|
0.00%
0/36
|
2.9%
1/35
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
0.00%
0/35
|
0.00%
0/36
|
2.9%
1/35
|
Other adverse events
| Measure |
Vandetanib 100 mg Plus FOLFIRI
n=35 participants at risk
vandetanib 100 mg plus FOLFIRI
|
Vandetanib 300 mg Plus FOLFIRI
n=36 participants at risk
vandetanib 300 mg plus FOLFIRI
|
Placebo Plus FOLFIRI
n=35 participants at risk
placebo plus FOLFIRI
|
|---|---|---|---|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
45.7%
16/35
|
47.2%
17/36
|
54.3%
19/35
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
5.7%
2/35
|
16.7%
6/36
|
8.6%
3/35
|
|
Blood and lymphatic system disorders
LEUKOPENIA
|
5.7%
2/35
|
5.6%
2/36
|
11.4%
4/35
|
|
Blood and lymphatic system disorders
ANAEMIA
|
2.9%
1/35
|
5.6%
2/36
|
8.6%
3/35
|
|
Gastrointestinal disorders
DIARRHOEA
|
51.4%
18/35
|
72.2%
26/36
|
48.6%
17/35
|
|
Gastrointestinal disorders
NAUSEA
|
48.6%
17/35
|
33.3%
12/36
|
51.4%
18/35
|
|
Gastrointestinal disorders
STOMATITIS
|
28.6%
10/35
|
41.7%
15/36
|
45.7%
16/35
|
|
Gastrointestinal disorders
VOMITING
|
25.7%
9/35
|
16.7%
6/36
|
34.3%
12/35
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
17.1%
6/35
|
11.1%
4/36
|
22.9%
8/35
|
|
Gastrointestinal disorders
CONSTIPATION
|
20.0%
7/35
|
16.7%
6/36
|
20.0%
7/35
|
|
Gastrointestinal disorders
DYSPEPSIA
|
11.4%
4/35
|
16.7%
6/36
|
17.1%
6/35
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
5.7%
2/35
|
2.8%
1/36
|
8.6%
3/35
|
|
Gastrointestinal disorders
FLATULENCE
|
8.6%
3/35
|
2.8%
1/36
|
0.00%
0/35
|
|
Gastrointestinal disorders
ORAL PAIN
|
8.6%
3/35
|
2.8%
1/36
|
0.00%
0/35
|
|
Gastrointestinal disorders
ABDOMINAL DISTENSION
|
2.9%
1/35
|
5.6%
2/36
|
2.9%
1/35
|
|
Gastrointestinal disorders
DRY MOUTH
|
0.00%
0/35
|
2.8%
1/36
|
5.7%
2/35
|
|
Gastrointestinal disorders
HAEMORRHOIDS
|
5.7%
2/35
|
0.00%
0/36
|
2.9%
1/35
|
|
Gastrointestinal disorders
PROCTALGIA
|
5.7%
2/35
|
2.8%
1/36
|
0.00%
0/35
|
|
General disorders
FATIGUE
|
28.6%
10/35
|
25.0%
9/36
|
25.7%
9/35
|
|
General disorders
ASTHENIA
|
20.0%
7/35
|
16.7%
6/36
|
17.1%
6/35
|
|
General disorders
PYREXIA
|
17.1%
6/35
|
8.3%
3/36
|
8.6%
3/35
|
|
General disorders
OEDEMA PERIPHERAL
|
2.9%
1/35
|
8.3%
3/36
|
8.6%
3/35
|
|
General disorders
CHILLS
|
2.9%
1/35
|
2.8%
1/36
|
5.7%
2/35
|
|
General disorders
INJECTION SITE REACTION
|
5.7%
2/35
|
0.00%
0/36
|
2.9%
1/35
|
|
Infections and infestations
CENTRAL LINE INFECTION
|
0.00%
0/35
|
11.1%
4/36
|
5.7%
2/35
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
0.00%
0/35
|
11.1%
4/36
|
0.00%
0/35
|
|
Infections and infestations
NASOPHARYNGITIS
|
8.6%
3/35
|
2.8%
1/36
|
2.9%
1/35
|
|
Infections and infestations
URINARY TRACT INFECTION
|
2.9%
1/35
|
8.3%
3/36
|
5.7%
2/35
|
|
Infections and infestations
ELECTROCARDIOGRAM QT PROLONGED
|
11.4%
4/35
|
22.2%
8/36
|
2.9%
1/35
|
|
Metabolism and nutrition disorders
ANOREXIA
|
31.4%
11/35
|
27.8%
10/36
|
42.9%
15/35
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
2.9%
1/35
|
2.8%
1/36
|
8.6%
3/35
|
|
Metabolism and nutrition disorders
HYPOKALAEMIA
|
2.9%
1/35
|
8.3%
3/36
|
2.9%
1/35
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
5.7%
2/35
|
11.1%
4/36
|
5.7%
2/35
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL CHEST PAIN
|
5.7%
2/35
|
2.8%
1/36
|
0.00%
0/35
|
|
Nervous system disorders
LETHARGY
|
14.3%
5/35
|
5.6%
2/36
|
11.4%
4/35
|
|
Nervous system disorders
PERIPHERAL SENSORY NEUROPATHY
|
5.7%
2/35
|
5.6%
2/36
|
14.3%
5/35
|
|
Nervous system disorders
DIZZINESS
|
5.7%
2/35
|
11.1%
4/36
|
11.4%
4/35
|
|
Nervous system disorders
HEADACHE
|
5.7%
2/35
|
8.3%
3/36
|
2.9%
1/35
|
|
Nervous system disorders
CHOLINERGIC SYNDROME
|
0.00%
0/35
|
5.6%
2/36
|
2.9%
1/35
|
|
Nervous system disorders
DYSGEUSIA
|
5.7%
2/35
|
5.6%
2/36
|
5.7%
2/35
|
|
Psychiatric disorders
INSOMNIA
|
14.3%
5/35
|
5.6%
2/36
|
0.00%
0/35
|
|
Psychiatric disorders
ANXIETY
|
0.00%
0/35
|
8.3%
3/36
|
5.7%
2/35
|
|
Renal and urinary disorders
HAEMATURIA
|
0.00%
0/35
|
8.3%
3/36
|
0.00%
0/35
|
|
Renal and urinary disorders
DYSURIA
|
0.00%
0/35
|
5.6%
2/36
|
0.00%
0/35
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
8.6%
3/35
|
8.3%
3/36
|
8.6%
3/35
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
2.9%
1/35
|
11.1%
4/36
|
5.7%
2/35
|
|
Respiratory, thoracic and mediastinal disorders
EPISTAXIS
|
8.6%
3/35
|
11.1%
4/36
|
5.7%
2/35
|
|
Respiratory, thoracic and mediastinal disorders
DYSPHONIA
|
2.9%
1/35
|
8.3%
3/36
|
0.00%
0/35
|
|
Respiratory, thoracic and mediastinal disorders
HICCUPS
|
2.9%
1/35
|
5.6%
2/36
|
5.7%
2/35
|
|
Respiratory, thoracic and mediastinal disorders
RHINORRHOEA
|
5.7%
2/35
|
2.8%
1/36
|
0.00%
0/35
|
|
Skin and subcutaneous tissue disorders
RASH
|
22.9%
8/35
|
61.1%
22/36
|
17.1%
6/35
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
34.3%
12/35
|
27.8%
10/36
|
42.9%
15/35
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
5.7%
2/35
|
13.9%
5/36
|
5.7%
2/35
|
|
Skin and subcutaneous tissue disorders
DRY SKIN
|
2.9%
1/35
|
11.1%
4/36
|
5.7%
2/35
|
|
Skin and subcutaneous tissue disorders
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME
|
2.9%
1/35
|
5.6%
2/36
|
5.7%
2/35
|
|
Skin and subcutaneous tissue disorders
ACNE
|
0.00%
0/35
|
5.6%
2/36
|
2.9%
1/35
|
|
Skin and subcutaneous tissue disorders
DERMATITIS ACNEIFORM
|
0.00%
0/35
|
5.6%
2/36
|
2.9%
1/35
|
|
Skin and subcutaneous tissue disorders
ERYTHEMA
|
5.7%
2/35
|
2.8%
1/36
|
0.00%
0/35
|
|
Skin and subcutaneous tissue disorders
HYPERHIDROSIS
|
2.9%
1/35
|
2.8%
1/36
|
5.7%
2/35
|
|
Skin and subcutaneous tissue disorders
PHOTOSENSITIVITY REACTION
|
5.7%
2/35
|
0.00%
0/36
|
0.00%
0/35
|
|
Skin and subcutaneous tissue disorders
SKIN EXFOLIATION
|
0.00%
0/35
|
5.6%
2/36
|
0.00%
0/35
|
|
Vascular disorders
HYPERTENSION
|
0.00%
0/35
|
11.1%
4/36
|
5.7%
2/35
|
|
Gastrointestinal disorders
SALIVARY HYPERSECRETION
|
0.00%
0/35
|
5.6%
2/36
|
0.00%
0/35
|
|
Gastrointestinal disorders
TOOTHACHE
|
0.00%
0/35
|
0.00%
0/36
|
5.7%
2/35
|
|
Hepatobiliary disorders
HYPERBILIRUBINAEMIA
|
0.00%
0/35
|
0.00%
0/36
|
5.7%
2/35
|
|
Eye disorders
LACRIMATION INCREASED
|
5.7%
2/35
|
0.00%
0/36
|
2.9%
1/35
|
|
Eye disorders
VISION BLURRED
|
0.00%
0/35
|
2.8%
1/36
|
5.7%
2/35
|
|
Infections and infestations
SKIN INFECTION
|
0.00%
0/35
|
5.6%
2/36
|
0.00%
0/35
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
5.7%
2/35
|
0.00%
0/36
|
2.9%
1/35
|
|
Musculoskeletal and connective tissue disorders
PAIN IN JAW
|
0.00%
0/35
|
5.6%
2/36
|
0.00%
0/35
|
|
Respiratory, thoracic and mediastinal disorders
HAEMOTHORAX
|
0.00%
0/35
|
5.6%
2/36
|
0.00%
0/35
|
|
Skin and subcutaneous tissue disorders
NAIL DISORDER
|
0.00%
0/35
|
0.00%
0/36
|
5.7%
2/35
|
|
Skin and subcutaneous tissue disorders
RASH MACULAR
|
0.00%
0/35
|
5.6%
2/36
|
0.00%
0/35
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER