Trial Outcomes & Findings for A Phase II Study of 2 Doses of ZD6474 (Vandetanib) in Combination With FOLFOX vs FOLFOX Alone for the Treatment of Colorectal Cancer (NCT NCT00500292)
NCT ID: NCT00500292
Last Updated: 2018-01-25
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
109 participants
Primary outcome timeframe
RECIST 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 (5 March 2008 +/-3 days)
Results posted on
2018-01-25
Participant Flow
First patient randomised 19 March 2007, last patient randomised 11 Nov 2007, data cut off date 8 March 2008. 109 patients were enrolled in the study.
109 patients were enrolled/screened to the study but only 104 patients were entered treatment/randomized.
Participant milestones
| Measure |
Vandetanib 100 mg Plus FOLFOX
vandetanib 100 mg plus FOLFOX
|
Vandetanib 300 mg Plus FOLFOX
vandetanib 300 mg plus FOLFOX
|
Placebo Plus FOLFOX
placebo plus FOLFOX
|
|---|---|---|---|
|
Overall Study
STARTED
|
32
|
35
|
37
|
|
Overall Study
COMPLETED
|
7
|
4
|
10
|
|
Overall Study
NOT COMPLETED
|
25
|
31
|
27
|
Reasons for withdrawal
| Measure |
Vandetanib 100 mg Plus FOLFOX
vandetanib 100 mg plus FOLFOX
|
Vandetanib 300 mg Plus FOLFOX
vandetanib 300 mg plus FOLFOX
|
Placebo Plus FOLFOX
placebo plus FOLFOX
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
3
|
6
|
4
|
|
Overall Study
Condition under investigation worsened
|
21
|
23
|
19
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
|
Overall Study
Other
|
1
|
1
|
4
|
Baseline Characteristics
A Phase II Study of 2 Doses of ZD6474 (Vandetanib) in Combination With FOLFOX vs FOLFOX Alone for the Treatment of Colorectal Cancer
Baseline characteristics by cohort
| Measure |
Vandetanib 100 mg Plus FOLFOX
n=32 Participants
vandetanib 100 mg plus FOLFOX
|
Vandetanib 300 mg Plus FOLFOX
n=35 Participants
vandetanib 300 mg plus FOLFOX
|
Placebo Plus FOLFOX
n=37 Participants
placebo plus FOLFOX
|
Total
n=104 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
57 Years
n=5 Participants
|
58 Years
n=7 Participants
|
59 Years
n=5 Participants
|
58 Years
n=4 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
40 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
64 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: RECIST 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 (5 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 FOLFOX
n=32 Participants
vandetanib 100 mg plus FOLFOX
|
Vandetanib 300 mg Plus FOLFOX
n=35 Participants
vandetanib 300 mg plus FOLFOX
|
Placebo Plus FOLFOX
n=37 Participants
placebo plus FOLFOX
|
|---|---|---|---|
|
Number of Patients With an Objective Disease Progression Event
|
23 Participants
|
27 Participants
|
24 Participants
|
Adverse Events
Vandetanib 100 mg
Serious events: 6 serious events
Other events: 31 other events
Deaths: 0 deaths
Vandetanib 300 mg
Serious events: 10 serious events
Other events: 32 other events
Deaths: 0 deaths
Placebo
Serious events: 4 serious events
Other events: 35 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Vandetanib 100 mg
n=32 participants at risk
vandetanib 100 mg plus FOLFOX
|
Vandetanib 300 mg
n=35 participants at risk
vandetanib 300 mg plus FOLFOX
|
Placebo
n=37 participants at risk
placebo plus FOLFOX
|
|---|---|---|---|
|
Cardiac disorders
Angina Pectoris
|
0.00%
0/32
|
0.00%
0/35
|
2.7%
1/37
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/32
|
2.9%
1/35
|
0.00%
0/37
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/32
|
2.9%
1/35
|
0.00%
0/37
|
|
Gastrointestinal disorders
Intestinal Obstruction
|
0.00%
0/32
|
0.00%
0/35
|
2.7%
1/37
|
|
Gastrointestinal disorders
Subileus
|
0.00%
0/32
|
2.9%
1/35
|
0.00%
0/37
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/32
|
0.00%
0/35
|
2.7%
1/37
|
|
General disorders
Mucosal Inflammation
|
0.00%
0/32
|
2.9%
1/35
|
0.00%
0/37
|
|
General disorders
Pyrexia
|
0.00%
0/32
|
2.9%
1/35
|
2.7%
1/37
|
|
Immune system disorders
Anaphylactic Reaction
|
0.00%
0/32
|
0.00%
0/35
|
2.7%
1/37
|
|
Infections and infestations
Appendicitis
|
0.00%
0/32
|
2.9%
1/35
|
0.00%
0/37
|
|
Infections and infestations
Device Related Infection
|
6.2%
2/32
|
0.00%
0/35
|
0.00%
0/37
|
|
Infections and infestations
Lung Abscess
|
0.00%
0/32
|
2.9%
1/35
|
0.00%
0/37
|
|
Infections and infestations
Pneumonia
|
3.1%
1/32
|
8.6%
3/35
|
0.00%
0/37
|
|
Infections and infestations
Staphylococcal Infection
|
0.00%
0/32
|
2.9%
1/35
|
0.00%
0/37
|
|
Infections and infestations
Staphylococcal Sepsis
|
0.00%
0/32
|
2.9%
1/35
|
0.00%
0/37
|
|
Injury, poisoning and procedural complications
Contusion
|
3.1%
1/32
|
0.00%
0/35
|
0.00%
0/37
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
0.00%
0/32
|
2.9%
1/35
|
0.00%
0/37
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/32
|
2.9%
1/35
|
0.00%
0/37
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma Gastric
|
3.1%
1/32
|
0.00%
0/35
|
0.00%
0/37
|
|
Nervous system disorders
Haemorrhage Intracranial
|
0.00%
0/32
|
2.9%
1/35
|
0.00%
0/37
|
|
Reproductive system and breast disorders
Female Genital Tract Fistula
|
3.1%
1/32
|
0.00%
0/35
|
0.00%
0/37
|
|
Skin and subcutaneous tissue disorders
Toxic Epidermal Necrolysis
|
0.00%
0/32
|
2.9%
1/35
|
0.00%
0/37
|
|
Vascular disorders
Hypertension
|
3.1%
1/32
|
0.00%
0/35
|
0.00%
0/37
|
|
Vascular disorders
Venous Thrombosis
|
3.1%
1/32
|
0.00%
0/35
|
0.00%
0/37
|
Other adverse events
| Measure |
Vandetanib 100 mg
n=32 participants at risk
vandetanib 100 mg plus FOLFOX
|
Vandetanib 300 mg
n=35 participants at risk
vandetanib 300 mg plus FOLFOX
|
Placebo
n=37 participants at risk
placebo plus FOLFOX
|
|---|---|---|---|
|
General disorders
Oedema Peripheral
|
3.1%
1/32
|
5.7%
2/35
|
2.7%
1/37
|
|
General disorders
Pyrexia
|
9.4%
3/32
|
14.3%
5/35
|
24.3%
9/37
|
|
Hepatobiliary disorders
Hepatotoxicity
|
0.00%
0/32
|
5.7%
2/35
|
0.00%
0/37
|
|
Blood and lymphatic system disorders
Leukopenia
|
12.5%
4/32
|
14.3%
5/35
|
13.5%
5/37
|
|
Blood and lymphatic system disorders
Neutropenia
|
40.6%
13/32
|
31.4%
11/35
|
35.1%
13/37
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
50.0%
16/32
|
51.4%
18/35
|
35.1%
13/37
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/32
|
0.00%
0/35
|
5.4%
2/37
|
|
Eye disorders
Vision Blurred
|
0.00%
0/32
|
5.7%
2/35
|
2.7%
1/37
|
|
Gastrointestinal disorders
Abdominal Distension
|
6.2%
2/32
|
8.6%
3/35
|
5.4%
2/37
|
|
Gastrointestinal disorders
Abdominal Pain
|
6.2%
2/32
|
8.6%
3/35
|
27.0%
10/37
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
6.2%
2/32
|
2.9%
1/35
|
10.8%
4/37
|
|
Gastrointestinal disorders
Constipation
|
18.8%
6/32
|
8.6%
3/35
|
16.2%
6/37
|
|
Gastrointestinal disorders
Diarrhoea
|
50.0%
16/32
|
62.9%
22/35
|
43.2%
16/37
|
|
Gastrointestinal disorders
Epigastric Discomfort
|
0.00%
0/32
|
5.7%
2/35
|
0.00%
0/37
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/32
|
0.00%
0/35
|
5.4%
2/37
|
|
Gastrointestinal disorders
Gingival Bleeding
|
0.00%
0/32
|
5.7%
2/35
|
0.00%
0/37
|
|
Gastrointestinal disorders
Nausea
|
40.6%
13/32
|
42.9%
15/35
|
64.9%
24/37
|
|
Gastrointestinal disorders
Rectal Haemorrhage
|
0.00%
0/32
|
0.00%
0/35
|
5.4%
2/37
|
|
Gastrointestinal disorders
Stomatitis
|
25.0%
8/32
|
31.4%
11/35
|
27.0%
10/37
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/32
|
2.9%
1/35
|
5.4%
2/37
|
|
Gastrointestinal disorders
Vomiting
|
28.1%
9/32
|
14.3%
5/35
|
37.8%
14/37
|
|
General disorders
Asthenia
|
12.5%
4/32
|
22.9%
8/35
|
16.2%
6/37
|
|
General disorders
Chills
|
3.1%
1/32
|
2.9%
1/35
|
5.4%
2/37
|
|
General disorders
Fatigue
|
25.0%
8/32
|
28.6%
10/35
|
40.5%
15/37
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/32
|
0.00%
0/35
|
5.4%
2/37
|
|
Immune system disorders
Drug Hypersensitivity
|
9.4%
3/32
|
11.4%
4/35
|
13.5%
5/37
|
|
Infections and infestations
Bronchitis
|
0.00%
0/32
|
5.7%
2/35
|
2.7%
1/37
|
|
Infections and infestations
Nasopharyngitis
|
12.5%
4/32
|
2.9%
1/35
|
5.4%
2/37
|
|
Infections and infestations
Pharyngitis
|
6.2%
2/32
|
2.9%
1/35
|
0.00%
0/37
|
|
Investigations
Electrocardiogram Qt Prolonged
|
3.1%
1/32
|
17.1%
6/35
|
2.7%
1/37
|
|
Investigations
Weight Decreased
|
9.4%
3/32
|
2.9%
1/35
|
5.4%
2/37
|
|
Metabolism and nutrition disorders
Anorexia
|
31.2%
10/32
|
31.4%
11/35
|
24.3%
9/37
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
0.00%
0/32
|
0.00%
0/35
|
5.4%
2/37
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
15.6%
5/32
|
11.4%
4/35
|
10.8%
4/37
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
6.2%
2/32
|
0.00%
0/35
|
2.7%
1/37
|
|
Nervous system disorders
Dizziness
|
6.2%
2/32
|
5.7%
2/35
|
8.1%
3/37
|
|
Nervous system disorders
Dysaesthesia
|
3.1%
1/32
|
2.9%
1/35
|
8.1%
3/37
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/32
|
0.00%
0/35
|
5.4%
2/37
|
|
Nervous system disorders
Headache
|
6.2%
2/32
|
14.3%
5/35
|
5.4%
2/37
|
|
Nervous system disorders
Lethargy
|
6.2%
2/32
|
0.00%
0/35
|
2.7%
1/37
|
|
Nervous system disorders
Paraesthesia
|
12.5%
4/32
|
14.3%
5/35
|
8.1%
3/37
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
50.0%
16/32
|
34.3%
12/35
|
48.6%
18/37
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/32
|
8.6%
3/35
|
0.00%
0/37
|
|
Psychiatric disorders
Confusional State
|
0.00%
0/32
|
5.7%
2/35
|
0.00%
0/37
|
|
Psychiatric disorders
Insomnia
|
9.4%
3/32
|
8.6%
3/35
|
8.1%
3/37
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/32
|
5.7%
2/35
|
2.7%
1/37
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/32
|
5.7%
2/35
|
0.00%
0/37
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
18.8%
6/32
|
2.9%
1/35
|
8.1%
3/37
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
9.4%
3/32
|
11.4%
4/35
|
5.4%
2/37
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
6.2%
2/32
|
8.6%
3/35
|
10.8%
4/37
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal Pain
|
6.2%
2/32
|
2.9%
1/35
|
0.00%
0/37
|
|
Skin and subcutaneous tissue disorders
Acne
|
9.4%
3/32
|
5.7%
2/35
|
8.1%
3/37
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
9.4%
3/32
|
2.9%
1/35
|
8.1%
3/37
|
|
Skin and subcutaneous tissue disorders
Dermatitis Acneiform
|
3.1%
1/32
|
14.3%
5/35
|
2.7%
1/37
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
6.2%
2/32
|
5.7%
2/35
|
2.7%
1/37
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/32
|
5.7%
2/35
|
0.00%
0/37
|
|
Skin and subcutaneous tissue disorders
Palmar-Plantar Erythrodysaesthesia Syndrome
|
9.4%
3/32
|
8.6%
3/35
|
2.7%
1/37
|
|
Skin and subcutaneous tissue disorders
Photosensitivity Reaction
|
9.4%
3/32
|
20.0%
7/35
|
2.7%
1/37
|
|
Skin and subcutaneous tissue disorders
Pigmentation Disorder
|
3.1%
1/32
|
5.7%
2/35
|
2.7%
1/37
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
3.1%
1/32
|
5.7%
2/35
|
8.1%
3/37
|
|
Skin and subcutaneous tissue disorders
Rash
|
21.9%
7/32
|
20.0%
7/35
|
8.1%
3/37
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
3.1%
1/32
|
0.00%
0/35
|
5.4%
2/37
|
|
Vascular disorders
Hypertension
|
40.6%
13/32
|
37.1%
13/35
|
13.5%
5/37
|
|
Vascular disorders
Phlebitis
|
6.2%
2/32
|
2.9%
1/35
|
2.7%
1/37
|
|
Vascular disorders
Phlebitis Superficial
|
6.2%
2/32
|
2.9%
1/35
|
0.00%
0/37
|
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