Trial Outcomes & Findings for A Phase I/II Study of Cediranib (AZD2171) in Japanese Metastatic Colorectal Cancer Patients in Combination With FOLFOX (NCT NCT00494221)
NCT ID: NCT00494221
Last Updated: 2014-03-27
Results Overview
Number of months from randomisation until progressive disease based on RECIST (progression of target lesions, clear progression of existing non-target lesions or the appearance of one or more new lesions) or death in the absence of progression.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
172 participants
Primary outcome timeframe
RECIST at Baseline, Weeks 6, 12, 18, 24 and then every 12 weeks until progression through to a cut-off date of 13th Oct 2009 (based on approx 105 progression events observed across the 3 groups)
Results posted on
2014-03-27
Participant Flow
Randomised=ITT=Safety: Cediranib 20mg=58, Cediranib 30mg=56, Placebo=58
PFS \& OS: median based on Kaplan Meier analysis (i.e. adjusted for censored observations) but full range based on raw data (i.e. not adjusted for censored observations). OS: median non-estimable due to censored observations
Participant milestones
| Measure |
Cediranib 20 mg
FOLFOX + Cediranib 20 mg
|
Cediranib 30 mg
FOLFOX + Cediranib 30 mg
|
Placebo
FOLFOX + Placebo
|
|---|---|---|---|
|
Overall Study
STARTED
|
58
|
56
|
58
|
|
Overall Study
COMPLETED
|
42
|
45
|
44
|
|
Overall Study
NOT COMPLETED
|
16
|
11
|
14
|
Reasons for withdrawal
| Measure |
Cediranib 20 mg
FOLFOX + Cediranib 20 mg
|
Cediranib 30 mg
FOLFOX + Cediranib 30 mg
|
Placebo
FOLFOX + Placebo
|
|---|---|---|---|
|
Overall Study
Death
|
15
|
9
|
14
|
|
Overall Study
Withdrawal by Subject
|
1
|
2
|
0
|
Baseline Characteristics
A Phase I/II Study of Cediranib (AZD2171) in Japanese Metastatic Colorectal Cancer Patients in Combination With FOLFOX
Baseline characteristics by cohort
| Measure |
Cediranib 20 mg
n=58 Participants
FOLFOX + Cediranib 20 mg
|
Cediranib 30 mg
n=56 Participants
FOLFOX + Cediranib 30 mg
|
Placebo
n=58 Participants
FOLFOX + Placebo
|
Total
n=172 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
62.4 years
STANDARD_DEVIATION 9.3 • n=5 Participants
|
62.1 years
STANDARD_DEVIATION 9.9 • n=7 Participants
|
62.2 years
STANDARD_DEVIATION 9.6 • n=5 Participants
|
62.2 years
STANDARD_DEVIATION 9.5 • n=4 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
65 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
38 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
107 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: RECIST at Baseline, Weeks 6, 12, 18, 24 and then every 12 weeks until progression through to a cut-off date of 13th Oct 2009 (based on approx 105 progression events observed across the 3 groups)Number of months from randomisation until progressive disease based on RECIST (progression of target lesions, clear progression of existing non-target lesions or the appearance of one or more new lesions) or death in the absence of progression.
Outcome measures
| Measure |
Cediranib 20 mg
n=58 Participants
FOLFOX + Cediranib 20 mg
|
Cediranib 30 mg
n=56 Participants
FOLFOX + Cediranib 30 mg
|
Placebo
n=58 Participants
FOLFOX + Placebo
|
|---|---|---|---|
|
Progression Free Survival
|
10.23 Months
Interval 1.15 to 19.51
|
8.85 Months
Interval 0.0 to 19.47
|
8.32 Months
Interval 0.99 to 19.14
|
SECONDARY outcome
Timeframe: RECIST at Baseline, Weeks 6, 12, 18, 24 and then every 12 weeks until progression through to a cut-off date of 13th Oct 2009 (based on approx 105 progression events observed across the 3 groups)Number of patients with complete (CR) /partial response (PR) (based on RECIST). CR is defined as Disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of Longest Diameter (LD) of target lesions taking as reference the baseline sum LD.
Outcome measures
| Measure |
Cediranib 20 mg
n=58 Participants
FOLFOX + Cediranib 20 mg
|
Cediranib 30 mg
n=56 Participants
FOLFOX + Cediranib 30 mg
|
Placebo
n=58 Participants
FOLFOX + Placebo
|
|---|---|---|---|
|
Objective Tumour Response Rate
|
31 Participants
|
39 Participants
|
31 Participants
|
SECONDARY outcome
Timeframe: Randomisation until cut-off date 13OCT2009 (based on approximately 105 progression events observed across the 3 groups)Best percentage change in tumour size from baseline, based on the sum of the longest diameters of the target lesions
Outcome measures
| Measure |
Cediranib 20 mg
n=58 Participants
FOLFOX + Cediranib 20 mg
|
Cediranib 30 mg
n=54 Participants
FOLFOX + Cediranib 30 mg
|
Placebo
n=57 Participants
FOLFOX + Placebo
|
|---|---|---|---|
|
Best Percentage Change in Tumour Size
|
-36.56 Percentage
Standard Deviation 24.52
|
-43.99 Percentage
Standard Deviation 22.62
|
-40.22 Percentage
Standard Deviation 35.84
|
SECONDARY outcome
Timeframe: RECIST at Baseline, Weeks 6, 12, 18, 24 and then every 12 weeks until progression through to a cut-off date of 13th Oct 2009 (based on approx 105 progression events observed across the 3 groups)Number of months from Complete/Partial response until progression up to cut-off date 13OCT2009 (based on approximately 105 progression events observed across the 3 groups).
Outcome measures
| Measure |
Cediranib 20 mg
n=31 Participants
FOLFOX + Cediranib 20 mg
|
Cediranib 30 mg
n=39 Participants
FOLFOX + Cediranib 30 mg
|
Placebo
n=31 Participants
FOLFOX + Placebo
|
|---|---|---|---|
|
Duration of Response
|
13.26 Months
Standard Deviation 16.81
|
8.12 Months
Standard Deviation 6.18
|
10.42 Months
Standard Deviation 10.97
|
SECONDARY outcome
Timeframe: Randomisation until cut-off date 13OCT2009 (based on approximately 105 progression events observed across the 3 groups)Number of months until death (censored if still alive at date cut-off). Median non-estimable if \>50% of subjects within a group are censored.
Outcome measures
| Measure |
Cediranib 20 mg
n=58 Participants
FOLFOX + Cediranib 20 mg
|
Cediranib 30 mg
n=56 Participants
FOLFOX + Cediranib 30 mg
|
Placebo
n=58 Participants
FOLFOX + Placebo
|
|---|---|---|---|
|
Overall Survival
|
NA Months
Interval 5.33 to 20.69
Median non-estimable because \>50% of participants were censored
|
20.07 Months
Interval 0.59 to 20.53
|
19.51 Months
Interval 1.32 to 20.92
|
Adverse Events
Cediranib 20 mg
Serious events: 23 serious events
Other events: 58 other events
Deaths: 0 deaths
Cediranib 30 mg
Serious events: 22 serious events
Other events: 56 other events
Deaths: 0 deaths
Placebo
Serious events: 11 serious events
Other events: 58 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cediranib 20 mg
n=58 participants at risk
Cediranib 20 mg
|
Cediranib 30 mg
n=56 participants at risk
Cediranib 30 mg
|
Placebo
n=58 participants at risk
Placebo
|
|---|---|---|---|
|
Gastrointestinal disorders
Peritonitis
|
0.00%
0/58
|
0.00%
0/56
|
1.7%
1/58
|
|
Gastrointestinal disorders
Stomatitis
|
1.7%
1/58
|
1.8%
1/56
|
0.00%
0/58
|
|
Gastrointestinal disorders
Subileus
|
0.00%
0/58
|
0.00%
0/56
|
1.7%
1/58
|
|
General disorders
Pyrexia
|
5.2%
3/58
|
0.00%
0/56
|
0.00%
0/58
|
|
General disorders
Fatigue
|
3.4%
2/58
|
3.6%
2/56
|
0.00%
0/58
|
|
General disorders
Malaise
|
0.00%
0/58
|
0.00%
0/56
|
3.4%
2/58
|
|
Hepatobiliary disorders
Cholecystitis
|
1.7%
1/58
|
0.00%
0/56
|
0.00%
0/58
|
|
Hepatobiliary disorders
Hepatic Function Abnormal
|
1.7%
1/58
|
0.00%
0/56
|
0.00%
0/58
|
|
Immune system disorders
Anaphylactic Shock
|
0.00%
0/58
|
0.00%
0/56
|
1.7%
1/58
|
|
Infections and infestations
Pneumonia
|
3.4%
2/58
|
1.8%
1/56
|
0.00%
0/58
|
|
Infections and infestations
Abdominal Abscess
|
0.00%
0/58
|
0.00%
0/56
|
1.7%
1/58
|
|
Infections and infestations
Catheter Site Infection
|
0.00%
0/58
|
1.8%
1/56
|
0.00%
0/58
|
|
Infections and infestations
Wound Infection
|
0.00%
0/58
|
1.8%
1/56
|
0.00%
0/58
|
|
Injury, poisoning and procedural complications
Postoperative Ileus
|
1.7%
1/58
|
0.00%
0/56
|
0.00%
0/58
|
|
Investigations
Weight Decreased
|
3.4%
2/58
|
0.00%
0/56
|
0.00%
0/58
|
|
Investigations
Blood Creatinine Increased
|
1.7%
1/58
|
0.00%
0/56
|
0.00%
0/58
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
17.2%
10/58
|
8.9%
5/56
|
3.4%
2/58
|
|
Gastrointestinal disorders
Mesenteric Artery Thrombosis
|
0.00%
0/58
|
1.8%
1/56
|
0.00%
0/58
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/58
|
0.00%
0/56
|
1.7%
1/58
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
1.7%
1/58
|
0.00%
0/56
|
1.7%
1/58
|
|
Cardiac disorders
Cardiac Failure
|
0.00%
0/58
|
1.8%
1/56
|
0.00%
0/58
|
|
Cardiac disorders
Prinzmetal Angina
|
1.7%
1/58
|
0.00%
0/56
|
0.00%
0/58
|
|
Gastrointestinal disorders
Ileus
|
3.4%
2/58
|
0.00%
0/56
|
6.9%
4/58
|
|
Gastrointestinal disorders
Nausea
|
6.9%
4/58
|
3.6%
2/56
|
1.7%
1/58
|
|
Gastrointestinal disorders
Vomiting
|
3.4%
2/58
|
5.4%
3/56
|
1.7%
1/58
|
|
Gastrointestinal disorders
Diarrhoea
|
3.4%
2/58
|
3.6%
2/56
|
0.00%
0/58
|
|
Gastrointestinal disorders
Abdominal Pain
|
1.7%
1/58
|
1.8%
1/56
|
0.00%
0/58
|
|
Gastrointestinal disorders
Anal Haemorrhage
|
0.00%
0/58
|
1.8%
1/56
|
0.00%
0/58
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/58
|
0.00%
0/56
|
1.7%
1/58
|
|
Gastrointestinal disorders
Duodenal Perforation
|
0.00%
0/58
|
1.8%
1/56
|
0.00%
0/58
|
|
Gastrointestinal disorders
Gastritis
|
1.7%
1/58
|
0.00%
0/56
|
0.00%
0/58
|
|
Gastrointestinal disorders
Large Intestine Perforation
|
0.00%
0/58
|
1.8%
1/56
|
0.00%
0/58
|
|
Metabolism and nutrition disorders
Dehydration
|
3.4%
2/58
|
0.00%
0/56
|
0.00%
0/58
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/58
|
0.00%
0/56
|
1.7%
1/58
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
1.7%
1/58
|
0.00%
0/56
|
0.00%
0/58
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bile Duct Cancer
|
0.00%
0/58
|
1.8%
1/56
|
0.00%
0/58
|
|
Nervous system disorders
Altered State Of Consciousness
|
0.00%
0/58
|
1.8%
1/56
|
0.00%
0/58
|
|
Nervous system disorders
Brain Stem Infarction
|
1.7%
1/58
|
0.00%
0/56
|
0.00%
0/58
|
|
Nervous system disorders
Cerebral Haemorrhage
|
0.00%
0/58
|
1.8%
1/56
|
0.00%
0/58
|
|
Nervous system disorders
Dizziness
|
0.00%
0/58
|
1.8%
1/56
|
0.00%
0/58
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
0.00%
0/58
|
0.00%
0/56
|
1.7%
1/58
|
|
Nervous system disorders
Reversible Posterior Leukoencephalopathy Syndrome
|
0.00%
0/58
|
1.8%
1/56
|
0.00%
0/58
|
|
Psychiatric disorders
Disorientation
|
0.00%
0/58
|
1.8%
1/56
|
0.00%
0/58
|
|
Renal and urinary disorders
Renal Failure Acute
|
1.7%
1/58
|
0.00%
0/56
|
0.00%
0/58
|
|
Respiratory, thoracic and mediastinal disorders
Chylothorax
|
1.7%
1/58
|
0.00%
0/56
|
0.00%
0/58
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea Exertional
|
0.00%
0/58
|
1.8%
1/56
|
0.00%
0/58
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial Lung Disease
|
1.7%
1/58
|
1.8%
1/56
|
0.00%
0/58
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia Aspiration
|
1.7%
1/58
|
0.00%
0/56
|
0.00%
0/58
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/58
|
1.8%
1/56
|
0.00%
0/58
|
|
Vascular disorders
Hypertension
|
0.00%
0/58
|
1.8%
1/56
|
0.00%
0/58
|
Other adverse events
| Measure |
Cediranib 20 mg
n=58 participants at risk
Cediranib 20 mg
|
Cediranib 30 mg
n=56 participants at risk
Cediranib 30 mg
|
Placebo
n=58 participants at risk
Placebo
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
10.3%
6/58
|
12.5%
7/56
|
5.2%
3/58
|
|
Blood and lymphatic system disorders
Neutropenia
|
10.3%
6/58
|
5.4%
3/56
|
1.7%
1/58
|
|
Endocrine disorders
Hypothyroidism
|
8.6%
5/58
|
10.7%
6/56
|
1.7%
1/58
|
|
Gastrointestinal disorders
Diarrhoea
|
89.7%
52/58
|
85.7%
48/56
|
37.9%
22/58
|
|
Gastrointestinal disorders
Nausea
|
63.8%
37/58
|
64.3%
36/56
|
63.8%
37/58
|
|
Gastrointestinal disorders
Stomatitis
|
55.2%
32/58
|
51.8%
29/56
|
43.1%
25/58
|
|
Gastrointestinal disorders
Vomiting
|
39.7%
23/58
|
48.2%
27/56
|
24.1%
14/58
|
|
Gastrointestinal disorders
Constipation
|
36.2%
21/58
|
25.0%
14/56
|
25.9%
15/58
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
5.2%
3/58
|
7.1%
4/56
|
13.8%
8/58
|
|
Gastrointestinal disorders
Haemorrhoids
|
10.3%
6/58
|
0.00%
0/56
|
1.7%
1/58
|
|
Gastrointestinal disorders
Abdominal Pain
|
5.2%
3/58
|
8.9%
5/56
|
6.9%
4/58
|
|
Gastrointestinal disorders
Cheilitis
|
8.6%
5/58
|
5.4%
3/56
|
6.9%
4/58
|
|
Gastrointestinal disorders
Gingivitis
|
8.6%
5/58
|
8.9%
5/56
|
1.7%
1/58
|
|
Gastrointestinal disorders
Dental Caries
|
6.9%
4/58
|
0.00%
0/56
|
1.7%
1/58
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/58
|
5.4%
3/56
|
6.9%
4/58
|
|
Gastrointestinal disorders
Periodontitis
|
6.9%
4/58
|
1.8%
1/56
|
0.00%
0/58
|
|
Gastrointestinal disorders
Abdominal Distension
|
1.7%
1/58
|
5.4%
3/56
|
0.00%
0/58
|
|
Gastrointestinal disorders
Anal Haemorrhage
|
3.4%
2/58
|
5.4%
3/56
|
1.7%
1/58
|
|
Gastrointestinal disorders
Ascites
|
5.2%
3/58
|
1.8%
1/56
|
0.00%
0/58
|
|
Gastrointestinal disorders
Glossitis
|
5.2%
3/58
|
1.8%
1/56
|
1.7%
1/58
|
|
Gastrointestinal disorders
Toothache
|
5.2%
3/58
|
1.8%
1/56
|
3.4%
2/58
|
|
General disorders
Fatigue
|
65.5%
38/58
|
71.4%
40/56
|
62.1%
36/58
|
|
General disorders
Pyrexia
|
13.8%
8/58
|
21.4%
12/56
|
19.0%
11/58
|
|
General disorders
Oedema Peripheral
|
8.6%
5/58
|
12.5%
7/56
|
3.4%
2/58
|
|
General disorders
Influenza Like Illness
|
6.9%
4/58
|
5.4%
3/56
|
8.6%
5/58
|
|
General disorders
Mucosal Inflammation
|
5.2%
3/58
|
1.8%
1/56
|
1.7%
1/58
|
|
Hepatobiliary disorders
Hepatic Function Abnormal
|
5.2%
3/58
|
5.4%
3/56
|
0.00%
0/58
|
|
Immune system disorders
Drug Hypersensitivity
|
10.3%
6/58
|
16.1%
9/56
|
20.7%
12/58
|
|
Infections and infestations
Nasopharyngitis
|
24.1%
14/58
|
17.9%
10/56
|
10.3%
6/58
|
|
Infections and infestations
Oral Candidiasis
|
6.9%
4/58
|
1.8%
1/56
|
0.00%
0/58
|
|
Infections and infestations
Cystitis
|
5.2%
3/58
|
0.00%
0/56
|
1.7%
1/58
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
65.5%
38/58
|
75.0%
42/56
|
65.5%
38/58
|
|
Metabolism and nutrition disorders
Dehydration
|
5.2%
3/58
|
3.6%
2/56
|
0.00%
0/58
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
19.0%
11/58
|
8.9%
5/56
|
8.6%
5/58
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
5.2%
3/58
|
7.1%
4/56
|
1.7%
1/58
|
|
Nervous system disorders
Neuropathy Peripheral
|
72.4%
42/58
|
62.5%
35/56
|
65.5%
38/58
|
|
Nervous system disorders
Dysgeusia
|
31.0%
18/58
|
30.4%
17/56
|
31.0%
18/58
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
12.1%
7/58
|
26.8%
15/56
|
19.0%
11/58
|
|
Nervous system disorders
Headache
|
10.3%
6/58
|
10.7%
6/56
|
10.3%
6/58
|
|
Psychiatric disorders
Insomnia
|
6.9%
4/58
|
3.6%
2/56
|
5.2%
3/58
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
41.4%
24/58
|
28.6%
16/56
|
3.4%
2/58
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
25.9%
15/58
|
33.9%
19/56
|
15.5%
9/58
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
12.1%
7/58
|
7.1%
4/56
|
10.3%
6/58
|
|
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Tract Inflammation
|
0.00%
0/58
|
8.9%
5/56
|
3.4%
2/58
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.9%
4/58
|
5.4%
3/56
|
3.4%
2/58
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.7%
1/58
|
5.4%
3/56
|
0.00%
0/58
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
5.2%
3/58
|
3.6%
2/56
|
5.2%
3/58
|
|
Skin and subcutaneous tissue disorders
Palmar-Plantar Erythrodysaesthesia Syndrome
|
53.4%
31/58
|
60.7%
34/56
|
13.8%
8/58
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
20.7%
12/58
|
30.4%
17/56
|
25.9%
15/58
|
|
Skin and subcutaneous tissue disorders
Rash
|
20.7%
12/58
|
21.4%
12/56
|
13.8%
8/58
|
|
Skin and subcutaneous tissue disorders
Pigmentation Disorder
|
13.8%
8/58
|
8.9%
5/56
|
12.1%
7/58
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.9%
4/58
|
5.4%
3/56
|
12.1%
7/58
|
|
Skin and subcutaneous tissue disorders
Skin Hyperpigmentation
|
6.9%
4/58
|
12.5%
7/56
|
6.9%
4/58
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
8.6%
5/58
|
3.6%
2/56
|
3.4%
2/58
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
8.6%
5/58
|
0.00%
0/56
|
1.7%
1/58
|
|
Skin and subcutaneous tissue disorders
Dermatitis Contact
|
6.9%
4/58
|
7.1%
4/56
|
1.7%
1/58
|
|
Skin and subcutaneous tissue disorders
Haemorrhage Subcutaneous
|
6.9%
4/58
|
3.6%
2/56
|
0.00%
0/58
|
|
Vascular disorders
Hypertension
|
81.0%
47/58
|
83.9%
47/56
|
31.0%
18/58
|
|
Vascular disorders
Hypotension
|
5.2%
3/58
|
0.00%
0/56
|
0.00%
0/58
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If a Study Site, or an investigator, requests permission to publish data from this study, any such publication (including oral presentations) is to be agreed with AstraZeneca prior to publication.
- Publication restrictions are in place
Restriction type: OTHER