Trial Outcomes & Findings for A Phase III Trial of ZD4054 (Zibotentan) (Endothelin A Antagonist) and Docetaxel in Metastatic Hormone Resistant Prostate Cancer (NCT NCT00617669)
NCT ID: NCT00617669
Last Updated: 2012-09-10
Results Overview
Median time (in months) from randomisation until death using the Kaplan-Meier method.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1494 participants
Primary outcome timeframe
Patients were followed for survival up to 40 months
Results posted on
2012-09-10
Participant Flow
1494 patients with hormone resistant prostate cancer patients and bone metastasis were recruited between 24th January 2008 and 10th May 2011
442 of the 1494 enrolled patients were not randomised to treatment groups as they failed screening.
Participant milestones
| Measure |
ZD4054 + Docetaxel
XD4054 10 mg oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
Placebo + Docetaxel
placebo oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
524
|
528
|
|
Overall Study
Patients Who Received IP
|
522
|
525
|
|
Overall Study
COMPLETED
|
94
|
77
|
|
Overall Study
NOT COMPLETED
|
430
|
451
|
Reasons for withdrawal
| Measure |
ZD4054 + Docetaxel
XD4054 10 mg oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
Placebo + Docetaxel
placebo oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
71
|
77
|
|
Overall Study
Lost to Follow-up
|
3
|
2
|
|
Overall Study
Adverse Event
|
87
|
76
|
|
Overall Study
Protocol Violation
|
2
|
3
|
|
Overall Study
Reason not otherwise captured, eg; death
|
265
|
290
|
|
Overall Study
Patients randomized but not treated
|
2
|
3
|
Baseline Characteristics
A Phase III Trial of ZD4054 (Zibotentan) (Endothelin A Antagonist) and Docetaxel in Metastatic Hormone Resistant Prostate Cancer
Baseline characteristics by cohort
| Measure |
ZD4054 + Docetaxel
n=524 Participants
XD4054 10 mg oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
Placebo + Docetaxel
n=528 Participants
placebo oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
Total
n=1052 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
overall
|
8.1 years
STANDARD_DEVIATION 67.7 • n=5 Participants
|
7.8 years
STANDARD_DEVIATION 67.6 • n=7 Participants
|
7.9 years
STANDARD_DEVIATION 67.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
524 Participants
n=5 Participants
|
528 Participants
n=7 Participants
|
1052 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Patients were followed for survival up to 40 monthsPopulation: Full Analysis Set
Median time (in months) from randomisation until death using the Kaplan-Meier method.
Outcome measures
| Measure |
ZD4054 + Docetaxel
n=524 Participants
XD4054 10 mg oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
Placebo + Docetaxel
n=528 Participants
placebo oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
|---|---|---|
|
Overall Survival
|
20.0 Months
Interval 11.6 to 32.0
|
19.2 Months
Interval 12.0 to 30.3
|
SECONDARY outcome
Timeframe: Patients were followed for progression up to 40 monthsPopulation: Full Analysis Set
Median time (in months) from randomisation until clinical progression of disease using the Kaplan-Meier method. Progression is defined, using RECIST, as a measurable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions, since baseline
Outcome measures
| Measure |
ZD4054 + Docetaxel
n=524 Participants
XD4054 10 mg oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
Placebo + Docetaxel
n=528 Participants
placebo oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
|---|---|---|
|
Progression Free Survival
|
7.0 Months
Interval 3.5 to 13.1
|
7.9 Months
Interval 4.0 to 12.6
|
SECONDARY outcome
Timeframe: While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)Population: Full Analysis Set
Median time (in months) from randomisation until occurrence of a skeletal related event using the Kaplan-Meier method, where skeletal related event is defined as the first occurrence of a pathological fracture, a vertebral compression fracture not related to trauma, prophylactic surgery or radiation for impending fracture or spinal cord compression, or a spinal cord compression.
Outcome measures
| Measure |
ZD4054 + Docetaxel
n=524 Participants
XD4054 10 mg oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
Placebo + Docetaxel
n=528 Participants
placebo oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
|---|---|---|
|
Incidence of Skeletal Related Events
|
17.4 Months
Interval 10.0 to 25.3
|
17.3 Months
Interval 10.3 to 26.0
|
SECONDARY outcome
Timeframe: While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)Median time (in months) from randomisation until first PSA value \>50% higher than baseline of at least 5ng/ml seen in at least 2 consecutive PSA values at least 2 weeks apart using the Kaplan-Meier method.
Outcome measures
| Measure |
ZD4054 + Docetaxel
n=524 Participants
XD4054 10 mg oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
Placebo + Docetaxel
n=528 Participants
placebo oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
|---|---|---|
|
Time to Prostate-specific Antigen (PSA) Progression
|
11.9 Months
Interval 6.2 to 19.6
|
12.1 Months
Interval 6.0 to 18.3
|
SECONDARY outcome
Timeframe: While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)Population: Full Analysis Set
Median time (in months) from randomisation until date of first assessment of increased pain using the Kaplan-Meier method, where increased pain event is defined as the first of a patient requiring opiate medication for duration of ≥1 week for pain due to prostate cancer metastasis, pain due to metastasis that has an increase in the worst pain item of the Brief Pain Inventory (BPI) from baseline to a minimum score of 5 with no decrease in analgesic use, or pain due to metastasis requiring radionuclide therapy, radiation therapy or surgery.
Outcome measures
| Measure |
ZD4054 + Docetaxel
n=524 Participants
XD4054 10 mg oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
Placebo + Docetaxel
n=528 Participants
placebo oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
|---|---|---|
|
Time to Pain Progression
|
9.3 Months
Interval 3.9 to 18.4
|
10.0 Months
Interval 4.2 to 18.6
|
SECONDARY outcome
Timeframe: While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)Population: The Pain Response Analysis Set includes patients who were either receiving opiates at baseline (randomisation) or with a baseline BPI score ≥2.
Number of patients with a pain response, defined as a decrease in brief pain inventory questionnaire (BPI) of at least 2 points from baseline or a decrease in opiate use of 25% from baseline.
Outcome measures
| Measure |
ZD4054 + Docetaxel
n=362 Participants
XD4054 10 mg oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
Placebo + Docetaxel
n=373 Participants
placebo oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
|---|---|---|
|
Pain Response
|
255 Participants
|
276 Participants
|
SECONDARY outcome
Timeframe: While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)Population: Full Analysis Set
Median time (in months) from randomisation until deterioration of Health Related Quality of Life using the Kaplan-Meier method, where deterioration is defined as a change from baseline of less than or equal to -6 points in Total FACT-P score maintained for 2 consecutive visits.
Outcome measures
| Measure |
ZD4054 + Docetaxel
n=524 Participants
XD4054 10 mg oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
Placebo + Docetaxel
n=528 Participants
placebo oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
|---|---|---|
|
Health Related Quality of Life
|
4.4 Months
Interval 1.6 to 10.7
|
5.1 Months
Interval 2.1 to 12.0
|
SECONDARY outcome
Timeframe: While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)Population: Full Analysis Set
PSA response defined as \>50% decrease in serum PSA values from baseline seen in at least 2 consecutive PSA values at least 2 weeks apart.
Outcome measures
| Measure |
ZD4054 + Docetaxel
n=524 Participants
XD4054 10 mg oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
Placebo + Docetaxel
n=528 Participants
placebo oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
|---|---|---|
|
PSA Response
|
279 Participants
|
298 Participants
|
Adverse Events
ZD4054 + Docetaxel
Serious events: 214 serious events
Other events: 490 other events
Deaths: 0 deaths
Placebo + Docetaxel
Serious events: 203 serious events
Other events: 483 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
ZD4054 + Docetaxel
n=522 participants at risk
XD4054 10 mg oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
Placebo + Docetaxel
n=525 participants at risk
placebo oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
|---|---|---|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
4.2%
22/522
|
3.0%
16/525
|
|
Blood and lymphatic system disorders
Anaemia
|
3.6%
19/522
|
1.5%
8/525
|
|
Blood and lymphatic system disorders
Neutropenia
|
1.9%
10/522
|
2.3%
12/525
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.38%
2/522
|
0.76%
4/525
|
|
Blood and lymphatic system disorders
Coagulopathy
|
0.00%
0/522
|
0.19%
1/525
|
|
Blood and lymphatic system disorders
Lymphatic Obstruction
|
0.19%
1/522
|
0.00%
0/525
|
|
Cardiac disorders
Atrial Fibrillation
|
0.96%
5/522
|
0.38%
2/525
|
|
Cardiac disorders
Cardiac Failure
|
0.96%
5/522
|
0.38%
2/525
|
|
Cardiac disorders
Acute Myocardial Infarction
|
0.57%
3/522
|
0.76%
4/525
|
|
Cardiac disorders
Angina Pectoris
|
0.38%
2/522
|
0.38%
2/525
|
|
Cardiac disorders
Atrial Flutter
|
0.19%
1/522
|
0.38%
2/525
|
|
Cardiac disorders
Cardiac Failure Congestive
|
0.38%
2/522
|
0.00%
0/525
|
|
Cardiac disorders
Cardio-Respiratory Arrest
|
0.00%
0/522
|
0.38%
2/525
|
|
Cardiac disorders
Coronary Artery Stenosis
|
0.38%
2/522
|
0.00%
0/525
|
|
Cardiac disorders
Myocardial Infarction
|
0.38%
2/522
|
0.38%
2/525
|
|
Cardiac disorders
Myocardial Ischaemia
|
0.00%
0/522
|
0.38%
2/525
|
|
Cardiac disorders
Ventricular Tachycardia
|
0.00%
0/522
|
0.38%
2/525
|
|
Cardiac disorders
Angina Unstable
|
0.00%
0/522
|
0.19%
1/525
|
|
Cardiac disorders
Aortic Valve Disease
|
0.19%
1/522
|
0.00%
0/525
|
|
Cardiac disorders
Arrhythmia
|
0.00%
0/522
|
0.19%
1/525
|
|
Cardiac disorders
Bradycardia
|
0.19%
1/522
|
0.00%
0/525
|
|
Cardiac disorders
Cardiac Arrest
|
0.19%
1/522
|
0.19%
1/525
|
|
Cardiac disorders
Cardiopulmonary Failure
|
0.19%
1/522
|
0.00%
0/525
|
|
Cardiac disorders
Coronary Artery Disease
|
0.00%
0/522
|
0.19%
1/525
|
|
Cardiac disorders
Diastolic Dysfunction
|
0.00%
0/522
|
0.19%
1/525
|
|
Cardiac disorders
Hypertrophic Cardiomyopathy
|
0.19%
1/522
|
0.00%
0/525
|
|
Cardiac disorders
Left Ventricular Dysfunction
|
0.19%
1/522
|
0.00%
0/525
|
|
Cardiac disorders
Sinus Tachycardia
|
0.19%
1/522
|
0.00%
0/525
|
|
Endocrine disorders
Adrenal Insufficiency
|
0.19%
1/522
|
0.00%
0/525
|
|
Endocrine disorders
Adrenocortical Insufficiency Acute
|
0.00%
0/522
|
0.19%
1/525
|
|
Endocrine disorders
Inappropriate Antidiuretic Hormone Secretion
|
0.00%
0/522
|
0.19%
1/525
|
|
Eye disorders
Cataract
|
0.00%
0/522
|
0.19%
1/525
|
|
Eye disorders
Scleral Disorder
|
0.19%
1/522
|
0.00%
0/525
|
|
Eye disorders
Staphyloma
|
0.00%
0/522
|
0.19%
1/525
|
|
Eye disorders
Visual Acuity Reduced
|
0.19%
1/522
|
0.00%
0/525
|
|
Gastrointestinal disorders
Diarrhoea
|
1.1%
6/522
|
0.95%
5/525
|
|
Gastrointestinal disorders
Constipation
|
0.57%
3/522
|
0.57%
3/525
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/522
|
0.57%
3/525
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.38%
2/522
|
0.00%
0/525
|
|
Gastrointestinal disorders
Enterocolitis
|
0.38%
2/522
|
0.00%
0/525
|
|
Gastrointestinal disorders
Gastric Ulcer
|
0.19%
1/522
|
0.38%
2/525
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.19%
1/522
|
0.38%
2/525
|
|
Gastrointestinal disorders
Nausea
|
0.38%
2/522
|
0.00%
0/525
|
|
Gastrointestinal disorders
Upper Gastrointestinal Haemorrhage
|
0.38%
2/522
|
0.00%
0/525
|
|
Gastrointestinal disorders
Vomiting
|
0.38%
2/522
|
0.19%
1/525
|
|
Gastrointestinal disorders
Anal Fistula
|
0.00%
0/522
|
0.19%
1/525
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/522
|
0.19%
1/525
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/522
|
0.19%
1/525
|
|
Gastrointestinal disorders
Colitis Ischaemic
|
0.19%
1/522
|
0.00%
0/525
|
|
Gastrointestinal disorders
Colonic Polyp
|
0.19%
1/522
|
0.00%
0/525
|
|
Gastrointestinal disorders
Diarrhoea Haemorrhagic
|
0.00%
0/522
|
0.19%
1/525
|
|
Gastrointestinal disorders
Diverticulum
|
0.00%
0/522
|
0.19%
1/525
|
|
Gastrointestinal disorders
Duodenal Ulcer
|
0.19%
1/522
|
0.19%
1/525
|
|
Gastrointestinal disorders
Erosive Oesophagitis
|
0.19%
1/522
|
0.00%
0/525
|
|
Gastrointestinal disorders
Gastric Ulcer Haemorrhage
|
0.19%
1/522
|
0.00%
0/525
|
|
Gastrointestinal disorders
Gastritis
|
0.19%
1/522
|
0.19%
1/525
|
|
Gastrointestinal disorders
Gastrointestinal Haemorrhage
|
0.00%
0/522
|
0.19%
1/525
|
|
Gastrointestinal disorders
Haematemesis
|
0.19%
1/522
|
0.00%
0/525
|
|
Gastrointestinal disorders
Inguinal Hernia
|
0.00%
0/522
|
0.19%
1/525
|
|
Gastrointestinal disorders
Inguinal Hernia Strangulated
|
0.00%
0/522
|
0.19%
1/525
|
|
Gastrointestinal disorders
Intestinal Infarction
|
0.19%
1/522
|
0.00%
0/525
|
|
Gastrointestinal disorders
Irritable Bowel Syndrome
|
0.19%
1/522
|
0.00%
0/525
|
|
Gastrointestinal disorders
Large Intestinal Haemorrhage
|
0.19%
1/522
|
0.00%
0/525
|
|
Gastrointestinal disorders
Lower Gastrointestinal Haemorrhage
|
0.00%
0/522
|
0.19%
1/525
|
|
Gastrointestinal disorders
Melaena
|
0.00%
0/522
|
0.19%
1/525
|
|
Gastrointestinal disorders
Mouth Haemorrhage
|
0.19%
1/522
|
0.00%
0/525
|
|
Gastrointestinal disorders
Neutropenic Colitis
|
0.00%
0/522
|
0.19%
1/525
|
|
Gastrointestinal disorders
Oesophagitis Ulcerative
|
0.19%
1/522
|
0.00%
0/525
|
|
Gastrointestinal disorders
Rectal Haemorrhage
|
0.19%
1/522
|
0.00%
0/525
|
|
Gastrointestinal disorders
Rectourethral Fistula
|
0.19%
1/522
|
0.00%
0/525
|
|
Gastrointestinal disorders
Small Intestinal Obstruction
|
0.19%
1/522
|
0.19%
1/525
|
|
General disorders
Pyrexia
|
1.1%
6/522
|
2.3%
12/525
|
|
General disorders
Death
|
1.9%
10/522
|
1.1%
6/525
|
|
General disorders
Oedema Peripheral
|
1.1%
6/522
|
0.57%
3/525
|
|
General disorders
General Physical Health Deterioration
|
0.00%
0/522
|
0.57%
3/525
|
|
General disorders
Asthenia
|
0.00%
0/522
|
0.38%
2/525
|
|
General disorders
Disease Progression
|
0.19%
1/522
|
0.38%
2/525
|
|
General disorders
Medical Device Complication
|
0.00%
0/522
|
0.38%
2/525
|
|
General disorders
Chest Pain
|
0.19%
1/522
|
0.00%
0/525
|
|
General disorders
Device Occlusion
|
0.19%
1/522
|
0.19%
1/525
|
|
General disorders
Pain
|
0.19%
1/522
|
0.00%
0/525
|
|
General disorders
Sudden Death
|
0.19%
1/522
|
0.00%
0/525
|
|
Hepatobiliary disorders
Cholecystitis Acute
|
0.00%
0/522
|
0.19%
1/525
|
|
Hepatobiliary disorders
Hepatic Cirrhosis
|
0.00%
0/522
|
0.19%
1/525
|
|
Hepatobiliary disorders
Hypertransaminasaemia
|
0.19%
1/522
|
0.00%
0/525
|
|
Immune system disorders
Drug Hypersensitivity
|
0.38%
2/522
|
0.00%
0/525
|
|
Immune system disorders
Hypersensitivity
|
0.19%
1/522
|
0.19%
1/525
|
|
Infections and infestations
Pneumonia
|
5.0%
26/522
|
1.5%
8/525
|
|
Infections and infestations
Sepsis
|
1.9%
10/522
|
0.38%
2/525
|
|
Infections and infestations
Urinary Tract Infection
|
1.7%
9/522
|
1.3%
7/525
|
|
Infections and infestations
Urosepsis
|
0.77%
4/522
|
0.95%
5/525
|
|
Infections and infestations
Cellulitis
|
0.77%
4/522
|
0.19%
1/525
|
|
Infections and infestations
Neutropenic Sepsis
|
0.77%
4/522
|
0.57%
3/525
|
|
Infections and infestations
Bronchopneumonia
|
0.57%
3/522
|
0.38%
2/525
|
|
Infections and infestations
Lung Infection
|
0.57%
3/522
|
0.00%
0/525
|
|
Infections and infestations
Bronchitis
|
0.38%
2/522
|
0.19%
1/525
|
|
Infections and infestations
Cystitis
|
0.38%
2/522
|
0.00%
0/525
|
|
Infections and infestations
Gastroenteritis
|
0.38%
2/522
|
0.38%
2/525
|
|
Infections and infestations
Infection
|
0.00%
0/522
|
0.38%
2/525
|
|
Infections and infestations
Lobar Pneumonia
|
0.00%
0/522
|
0.38%
2/525
|
|
Infections and infestations
Lower Respiratory Tract Infection
|
0.38%
2/522
|
0.38%
2/525
|
|
Infections and infestations
Pharyngitis
|
0.38%
2/522
|
0.00%
0/525
|
|
Infections and infestations
Pyelonephritis
|
0.38%
2/522
|
0.19%
1/525
|
|
Infections and infestations
Sinusitis
|
0.38%
2/522
|
0.00%
0/525
|
|
Infections and infestations
Skin Infection
|
0.38%
2/522
|
0.00%
0/525
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
0.38%
2/522
|
0.19%
1/525
|
|
Infections and infestations
Abscess
|
0.00%
0/522
|
0.19%
1/525
|
|
Infections and infestations
Abscess Limb
|
0.00%
0/522
|
0.19%
1/525
|
|
Infections and infestations
Anal Abscess
|
0.00%
0/522
|
0.19%
1/525
|
|
Infections and infestations
Appendicitis
|
0.19%
1/522
|
0.19%
1/525
|
|
Infections and infestations
Arthritis Bacterial
|
0.00%
0/522
|
0.19%
1/525
|
|
Infections and infestations
Arthritis Infective
|
0.00%
0/522
|
0.19%
1/525
|
|
Infections and infestations
Bacterial Diarrhoea
|
0.19%
1/522
|
0.00%
0/525
|
|
Infections and infestations
Catheter Site Infection
|
0.00%
0/522
|
0.19%
1/525
|
|
Infections and infestations
Clostridium Difficile Colitis
|
0.00%
0/522
|
0.19%
1/525
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/522
|
0.19%
1/525
|
|
Infections and infestations
Endocarditis
|
0.19%
1/522
|
0.00%
0/525
|
|
Infections and infestations
Erysipelas
|
0.00%
0/522
|
0.19%
1/525
|
|
Infections and infestations
Furuncle
|
0.00%
0/522
|
0.19%
1/525
|
|
Infections and infestations
Herpes Zoster
|
0.19%
1/522
|
0.00%
0/525
|
|
Infections and infestations
Labyrinthitis
|
0.19%
1/522
|
0.00%
0/525
|
|
Infections and infestations
Localised Infection
|
0.00%
0/522
|
0.19%
1/525
|
|
Infections and infestations
Lyme Disease
|
0.00%
0/522
|
0.19%
1/525
|
|
Infections and infestations
Necrotising Fasciitis
|
0.19%
1/522
|
0.00%
0/525
|
|
Infections and infestations
Neutropenic Infection
|
0.00%
0/522
|
0.19%
1/525
|
|
Infections and infestations
Otitis Media
|
0.19%
1/522
|
0.00%
0/525
|
|
Infections and infestations
Peritonitis Bacterial
|
0.19%
1/522
|
0.00%
0/525
|
|
Infections and infestations
Pneumocystis Jiroveci Pneumonia
|
0.00%
0/522
|
0.19%
1/525
|
|
Infections and infestations
Postoperative Wound Infection
|
0.00%
0/522
|
0.19%
1/525
|
|
Infections and infestations
Psoas Abscess
|
0.00%
0/522
|
0.19%
1/525
|
|
Infections and infestations
Pulmonary Tuberculosis
|
0.19%
1/522
|
0.00%
0/525
|
|
Infections and infestations
Respiratory Tract Infection
|
0.19%
1/522
|
0.19%
1/525
|
|
Infections and infestations
Staphylococcal Bacteraemia
|
0.19%
1/522
|
0.19%
1/525
|
|
Infections and infestations
Staphylococcal Infection
|
0.19%
1/522
|
0.00%
0/525
|
|
Infections and infestations
Subcutaneous Abscess
|
0.19%
1/522
|
0.00%
0/525
|
|
Infections and infestations
Tooth Infection
|
0.00%
0/522
|
0.19%
1/525
|
|
Infections and infestations
Tracheobronchitis
|
0.19%
1/522
|
0.00%
0/525
|
|
Injury, poisoning and procedural complications
Femoral Neck Fracture
|
0.38%
2/522
|
0.19%
1/525
|
|
Injury, poisoning and procedural complications
Subdural Haematoma
|
0.19%
1/522
|
0.38%
2/525
|
|
Injury, poisoning and procedural complications
Cerebral Haemorrhage Traumatic
|
0.00%
0/522
|
0.19%
1/525
|
|
Injury, poisoning and procedural complications
Facial Bones Fracture
|
0.19%
1/522
|
0.00%
0/525
|
|
Injury, poisoning and procedural complications
Hip Fracture
|
0.19%
1/522
|
0.19%
1/525
|
|
Injury, poisoning and procedural complications
Kidney Rupture
|
0.00%
0/522
|
0.19%
1/525
|
|
Injury, poisoning and procedural complications
Multiple Injuries
|
0.19%
1/522
|
0.00%
0/525
|
|
Injury, poisoning and procedural complications
Overdose
|
0.19%
1/522
|
0.00%
0/525
|
|
Injury, poisoning and procedural complications
Postoperative Wound Complication
|
0.00%
0/522
|
0.19%
1/525
|
|
Injury, poisoning and procedural complications
Radiation Pneumonitis
|
0.19%
1/522
|
0.00%
0/525
|
|
Injury, poisoning and procedural complications
Spinal Compression Fracture
|
0.00%
0/522
|
0.19%
1/525
|
|
Injury, poisoning and procedural complications
Stress Fracture
|
0.00%
0/522
|
0.19%
1/525
|
|
Injury, poisoning and procedural complications
Toxicity To Various Agents
|
0.19%
1/522
|
0.00%
0/525
|
|
Injury, poisoning and procedural complications
Wrist Fracture
|
0.19%
1/522
|
0.00%
0/525
|
|
Injury, poisoning and procedural complications
Haemoglobin Decreased
|
0.38%
2/522
|
0.00%
0/525
|
|
Injury, poisoning and procedural complications
Blood Electrolytes Abnormal
|
0.19%
1/522
|
0.00%
0/525
|
|
Injury, poisoning and procedural complications
Electrocardiogram QT Prolonged
|
0.00%
0/522
|
0.19%
1/525
|
|
Injury, poisoning and procedural complications
Neutrophil Count Decreased
|
0.00%
0/522
|
0.19%
1/525
|
|
Injury, poisoning and procedural complications
Transaminases Increased
|
0.00%
0/522
|
0.19%
1/525
|
|
Metabolism and nutrition disorders
Dehydration
|
1.3%
7/522
|
1.5%
8/525
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
1.1%
6/522
|
0.95%
5/525
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.77%
4/522
|
0.57%
3/525
|
|
Metabolism and nutrition disorders
Type 2 Diabetes Mellitus
|
0.00%
0/522
|
0.76%
4/525
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/522
|
0.38%
2/525
|
|
Metabolism and nutrition disorders
Diabetes Mellitus
|
0.00%
0/522
|
0.19%
1/525
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/522
|
0.19%
1/525
|
|
Metabolism and nutrition disorders
Hypernatraemia
|
0.19%
1/522
|
0.00%
0/525
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.19%
1/522
|
0.19%
1/525
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.19%
1/522
|
0.19%
1/525
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis Of Jaw
|
0.38%
2/522
|
0.38%
2/525
|
|
Musculoskeletal and connective tissue disorders
Pathological Fracture
|
0.19%
1/522
|
0.38%
2/525
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.19%
1/522
|
0.00%
0/525
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.19%
1/522
|
0.19%
1/525
|
|
Musculoskeletal and connective tissue disorders
Bone Pain
|
0.00%
0/522
|
0.19%
1/525
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
0.00%
0/522
|
0.19%
1/525
|
|
Musculoskeletal and connective tissue disorders
Muscular Weakness
|
0.00%
0/522
|
0.19%
1/525
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
0.19%
1/522
|
0.00%
0/525
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/522
|
0.19%
1/525
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
0.19%
1/522
|
0.19%
1/525
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid Arthritis
|
0.00%
0/522
|
0.19%
1/525
|
|
Musculoskeletal and connective tissue disorders
Synovitis
|
0.00%
0/522
|
0.19%
1/525
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Melanoma
|
0.00%
0/522
|
0.38%
2/525
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma
|
0.19%
1/522
|
0.00%
0/525
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder Transitional Cell Carcinoma
|
0.00%
0/522
|
0.19%
1/525
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colorectal Cancer
|
0.00%
0/522
|
0.19%
1/525
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastrointestinal Stromal Tumour
|
0.00%
0/522
|
0.19%
1/525
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lentigo Maligna Stage Unspecified
|
0.19%
1/522
|
0.00%
0/525
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Lymphoid Neoplasm
|
0.00%
0/522
|
0.19%
1/525
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal Cancer
|
0.19%
1/522
|
0.00%
0/525
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal Cell Carcinoma
|
0.19%
1/522
|
0.00%
0/525
|
|
Nervous system disorders
Cerebrovascular Accident
|
0.57%
3/522
|
0.19%
1/525
|
|
Nervous system disorders
Cerebral Haemorrhage
|
0.00%
0/522
|
0.38%
2/525
|
|
Nervous system disorders
Cerebral Infarction
|
0.19%
1/522
|
0.38%
2/525
|
|
Nervous system disorders
Presyncope
|
0.19%
1/522
|
0.38%
2/525
|
|
Nervous system disorders
Transient Ischaemic Attack
|
0.00%
0/522
|
0.38%
2/525
|
|
Nervous system disorders
Convulsion
|
0.00%
0/522
|
0.19%
1/525
|
|
Nervous system disorders
Depressed Level Of Consciousness
|
0.19%
1/522
|
0.00%
0/525
|
|
Nervous system disorders
Diabetic Neuropathy
|
0.19%
1/522
|
0.00%
0/525
|
|
Nervous system disorders
Dizziness
|
0.19%
1/522
|
0.00%
0/525
|
|
Nervous system disorders
Encephalopathy
|
0.19%
1/522
|
0.00%
0/525
|
|
Nervous system disorders
Ischaemic Stroke
|
0.19%
1/522
|
0.19%
1/525
|
|
Nervous system disorders
Neurotoxicity
|
0.19%
1/522
|
0.00%
0/525
|
|
Nervous system disorders
Paraplegia
|
0.19%
1/522
|
0.00%
0/525
|
|
Nervous system disorders
Radiculopathy
|
0.19%
1/522
|
0.00%
0/525
|
|
Nervous system disorders
Spinal Cord Compression
|
0.19%
1/522
|
0.19%
1/525
|
|
Nervous system disorders
Subarachnoid Haemorrhage
|
0.19%
1/522
|
0.19%
1/525
|
|
Nervous system disorders
Syncope
|
0.19%
1/522
|
0.19%
1/525
|
|
Psychiatric disorders
Completed Suicide
|
0.19%
1/522
|
0.57%
3/525
|
|
Psychiatric disorders
Confusional State
|
0.19%
1/522
|
0.00%
0/525
|
|
Psychiatric disorders
Delirium
|
0.00%
0/522
|
0.19%
1/525
|
|
Psychiatric disorders
Depression
|
0.00%
0/522
|
0.19%
1/525
|
|
Renal and urinary disorders
Renal Failure Acute
|
1.3%
7/522
|
0.38%
2/525
|
|
Renal and urinary disorders
Haematuria
|
0.38%
2/522
|
0.76%
4/525
|
|
Renal and urinary disorders
Urinary Retention
|
0.19%
1/522
|
0.38%
2/525
|
|
Renal and urinary disorders
Bladder Neck Obstruction
|
0.19%
1/522
|
0.00%
0/525
|
|
Renal and urinary disorders
Bladder Obstruction
|
0.19%
1/522
|
0.00%
0/525
|
|
Renal and urinary disorders
Calculus Ureteric
|
0.00%
0/522
|
0.19%
1/525
|
|
Renal and urinary disorders
Calculus Urinary
|
0.00%
0/522
|
0.19%
1/525
|
|
Renal and urinary disorders
Cystitis Noninfective
|
0.00%
0/522
|
0.19%
1/525
|
|
Renal and urinary disorders
Haemorrhage Urinary Tract
|
0.19%
1/522
|
0.00%
0/525
|
|
Renal and urinary disorders
Postrenal Failure
|
0.19%
1/522
|
0.00%
0/525
|
|
Renal and urinary disorders
Renal Colic
|
0.19%
1/522
|
0.00%
0/525
|
|
Renal and urinary disorders
Renal Failure
|
0.19%
1/522
|
0.00%
0/525
|
|
Renal and urinary disorders
Renal Tubular Necrosis
|
0.19%
1/522
|
0.00%
0/525
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
1.1%
6/522
|
1.3%
7/525
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/522
|
0.95%
5/525
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
0.57%
3/522
|
0.76%
4/525
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
0.77%
4/522
|
0.38%
2/525
|
|
Respiratory, thoracic and mediastinal disorders
Lung Disorder
|
0.38%
2/522
|
0.00%
0/525
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Distress
|
0.38%
2/522
|
0.19%
1/525
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome
|
0.19%
1/522
|
0.00%
0/525
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure
|
0.19%
1/522
|
0.00%
0/525
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis Chronic
|
0.00%
0/522
|
0.19%
1/525
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.19%
1/522
|
0.19%
1/525
|
|
Respiratory, thoracic and mediastinal disorders
Emphysema
|
0.19%
1/522
|
0.00%
0/525
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/522
|
0.19%
1/525
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial Lung Disease
|
0.00%
0/522
|
0.19%
1/525
|
|
Respiratory, thoracic and mediastinal disorders
Orthopnoea
|
0.00%
0/522
|
0.19%
1/525
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Haemorrhage
|
0.00%
0/522
|
0.19%
1/525
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.19%
1/522
|
0.19%
1/525
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/522
|
0.19%
1/525
|
|
Skin and subcutaneous tissue disorders
Skin Ulcer
|
0.19%
1/522
|
0.00%
0/525
|
|
Skin and subcutaneous tissue disorders
Stevens-Johnson Syndrome
|
0.00%
0/522
|
0.19%
1/525
|
|
Vascular disorders
Deep Vein Thrombosis
|
0.57%
3/522
|
0.38%
2/525
|
|
Vascular disorders
Aortic Aneurysm
|
0.38%
2/522
|
0.00%
0/525
|
|
Vascular disorders
Hypotension
|
0.38%
2/522
|
0.38%
2/525
|
|
Vascular disorders
Jugular Vein Thrombosis
|
0.00%
0/522
|
0.38%
2/525
|
|
Vascular disorders
Circulatory Collapse
|
0.00%
0/522
|
0.19%
1/525
|
|
Vascular disorders
Femoral Artery Occlusion
|
0.00%
0/522
|
0.19%
1/525
|
|
Vascular disorders
Haematoma
|
0.00%
0/522
|
0.19%
1/525
|
|
Vascular disorders
Hypertension
|
0.19%
1/522
|
0.00%
0/525
|
|
Vascular disorders
Hypovolaemic Shock
|
0.19%
1/522
|
0.19%
1/525
|
|
Vascular disorders
Shock
|
0.19%
1/522
|
0.00%
0/525
|
|
Vascular disorders
sThrombosis
|
0.00%
0/522
|
0.19%
1/525
|
Other adverse events
| Measure |
ZD4054 + Docetaxel
n=522 participants at risk
XD4054 10 mg oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
Placebo + Docetaxel
n=525 participants at risk
placebo oral tablet once daily + docetaxel intravenous infusion every 3 weeks
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
29.7%
155/522
|
22.1%
116/525
|
|
Blood and lymphatic system disorders
Neutropenia
|
21.8%
114/522
|
22.5%
118/525
|
|
Blood and lymphatic system disorders
Leukopenia
|
12.3%
64/522
|
11.4%
60/525
|
|
Eye disorders
Lacrimation Increased
|
7.3%
38/522
|
6.9%
36/525
|
|
Gastrointestinal disorders
Diarrhoea
|
35.1%
183/522
|
35.2%
185/525
|
|
Gastrointestinal disorders
Nausea
|
33.3%
174/522
|
30.5%
160/525
|
|
Gastrointestinal disorders
Constipation
|
29.1%
152/522
|
24.6%
129/525
|
|
Gastrointestinal disorders
Vomiting
|
21.1%
110/522
|
16.0%
84/525
|
|
Gastrointestinal disorders
Dyspepsia
|
4.0%
21/522
|
7.6%
40/525
|
|
Gastrointestinal disorders
Stomatitis
|
6.1%
32/522
|
6.7%
35/525
|
|
Gastrointestinal disorders
Abdominal Pain
|
4.8%
25/522
|
6.5%
34/525
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
5.9%
31/522
|
5.1%
27/525
|
|
General disorders
Oedema Peripheral
|
53.3%
278/522
|
35.8%
188/525
|
|
General disorders
Fatigue
|
28.7%
150/522
|
31.2%
164/525
|
|
General disorders
Asthenia
|
22.6%
118/522
|
22.3%
117/525
|
|
General disorders
Pyrexia
|
11.3%
59/522
|
11.4%
60/525
|
|
General disorders
Mucosal Inflammation
|
7.1%
37/522
|
5.3%
28/525
|
|
Infections and infestations
Rhinitis
|
9.8%
51/522
|
6.9%
36/525
|
|
Infections and infestations
Urinary Tract Infection
|
7.1%
37/522
|
9.1%
48/525
|
|
Infections and infestations
Nasopharyngitis
|
5.7%
30/522
|
6.9%
36/525
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
3.4%
18/522
|
5.1%
27/525
|
|
Infections and infestations
Weight Decreased
|
7.1%
37/522
|
7.0%
37/525
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
24.3%
127/522
|
22.7%
119/525
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
5.6%
29/522
|
3.2%
17/525
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
4.8%
25/522
|
5.1%
27/525
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
18.0%
94/522
|
17.3%
91/525
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
15.3%
80/522
|
16.4%
86/525
|
|
Musculoskeletal and connective tissue disorders
Pain In Extremity
|
13.6%
71/522
|
16.0%
84/525
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
8.0%
42/522
|
10.1%
53/525
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
8.8%
46/522
|
5.3%
28/525
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
4.2%
22/522
|
7.0%
37/525
|
|
Musculoskeletal and connective tissue disorders
Muscular Weakness
|
5.6%
29/522
|
7.0%
37/525
|
|
Musculoskeletal and connective tissue disorders
Bone Pain
|
5.4%
28/522
|
6.1%
32/525
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain
|
6.1%
32/522
|
3.8%
20/525
|
|
Nervous system disorders
Headache
|
20.5%
107/522
|
13.5%
71/525
|
|
Nervous system disorders
Dysgeusia
|
16.9%
88/522
|
13.9%
73/525
|
|
Nervous system disorders
Neuropathy Peripheral
|
9.4%
49/522
|
12.4%
65/525
|
|
Nervous system disorders
Paraesthesia
|
8.6%
45/522
|
9.1%
48/525
|
|
Nervous system disorders
Dizziness
|
8.2%
43/522
|
8.6%
45/525
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
7.9%
41/522
|
7.4%
39/525
|
|
Nervous system disorders
Hypoaesthesia
|
4.6%
24/522
|
5.3%
28/525
|
|
Psychiatric disorders
Insomnia
|
13.6%
71/522
|
11.2%
59/525
|
|
Renal and urinary disorders
Haematuria
|
5.7%
30/522
|
3.2%
17/525
|
|
Renal and urinary disorders
Dysuria
|
5.6%
29/522
|
3.6%
19/525
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
15.7%
82/522
|
13.7%
72/525
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.1%
58/522
|
14.9%
78/525
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
14.9%
78/522
|
5.0%
26/525
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea Exertional
|
8.2%
43/522
|
7.2%
38/525
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
5.0%
26/522
|
5.9%
31/525
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
34.1%
178/522
|
37.3%
196/525
|
|
Skin and subcutaneous tissue disorders
Rash
|
4.6%
24/522
|
7.6%
40/525
|
|
Skin and subcutaneous tissue disorders
Nail Discolouration
|
5.4%
28/522
|
7.4%
39/525
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
6.1%
32/522
|
5.3%
28/525
|
|
Skin and subcutaneous tissue disorders
Nail Disorder
|
4.4%
23/522
|
5.3%
28/525
|
|
Vascular disorders
Hypertension
|
3.1%
16/522
|
7.0%
37/525
|
|
Vascular disorders
Hypotension
|
6.3%
33/522
|
5.3%
28/525
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 3\. Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. AstraZeneca can review results communications prior to public release and may within 60 days of receipt require amendments to be made. AstraZeneca can also require that submission or disclosure be delayed to allow for
- Publication restrictions are in place
Restriction type: OTHER