Trial Outcomes & Findings for Cediranib (AZD2171, RECENTIN™) in Metastatic or Recurrent Renal Cell Carcinoma (NCT NCT00423332)

NCT ID: NCT00423332

Last Updated: 2017-02-02

Results Overview

Sum of longest diameters of the target lesions, based on Response Evaluation Criteria in Solid Tumours (RECIST) criteria ((Week 12 - baseline)/baseline)\*100

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

105 participants

Primary outcome timeframe

Baseline to Week 12

Results posted on

2017-02-02

Participant Flow

Seventy-one patients were randomised to study treatment: 53 to cediranib 45 mg and 18 to placebo. Following unblinding for the primary analysis, all patients, except those who had progressed on cediranib, then had the option of receiving open-label treatment with cediranib. Randomised=ITT=Safety set: Cediranib 45mg 53, Placebo 18.

Participant milestones

Participant milestones
Measure
AZD2171 45 mg
AZD2171 45mg/Day: 53 patients randomised
Placebo
Placebo / Day: 18 patients randomised
Overall Study
STARTED
53
18
Overall Study
Continuing After Unblinding
44
14
Overall Study
Ongoing at Data Cut Off (8th March 2009)
22
4
Overall Study
COMPLETED
44
11
Overall Study
NOT COMPLETED
9
7

Reasons for withdrawal

Reasons for withdrawal
Measure
AZD2171 45 mg
AZD2171 45mg/Day: 53 patients randomised
Placebo
Placebo / Day: 18 patients randomised
Overall Study
Adverse Event
6
2
Overall Study
Withdrawal by Subject
1
0
Overall Study
Condition under investigation worsened
1
1
Overall Study
Progressive at Week 6
0
1
Overall Study
Unblinded before 12 weeks
1
3

Baseline Characteristics

Cediranib (AZD2171, RECENTIN™) in Metastatic or Recurrent Renal Cell Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
AZD2171 45 mg
n=53 Participants
AZD2171 45mg/Day
Placebo
n=18 Participants
Placebo/Day
Total
n=71 Participants
Total of all reporting groups
Age, Continuous
60.7 Years
STANDARD_DEVIATION 7.7 • n=5 Participants
62.4 Years
STANDARD_DEVIATION 8.7 • n=7 Participants
61.2 Years
STANDARD_DEVIATION 7.9 • n=5 Participants
Gender
Female
13 Participants
n=5 Participants
3 Participants
n=7 Participants
16 Participants
n=5 Participants
Gender
Male
40 Participants
n=5 Participants
15 Participants
n=7 Participants
55 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 12

Population: For patients to be included in the analysis they had to have been evaluable for RECIST with week 12 or progression tumour size data

Sum of longest diameters of the target lesions, based on Response Evaluation Criteria in Solid Tumours (RECIST) criteria ((Week 12 - baseline)/baseline)\*100

Outcome measures

Outcome measures
Measure
AZD2171 45 mg
n=51 Participants
AZD2171 45mg/Day
Placebo
n=17 Participants
Placebo/Day
Percentage Change From Baseline in Tumour Size at 12 Weeks
-19.47 Percentage change from baseline
Standard Deviation 17.093
19.65 Percentage change from baseline
Standard Deviation 22.902

SECONDARY outcome

Timeframe: Treatment period up to Week 12 visit date for last patient in (LPI)

Population: For patients to be included in the analysis they had to have been evaluable for RECIST with week 12 or progression tumour size data.

Maximum reduction or minimum increase in tumour size where size is the sum of the longest diameters of the target lesions

Outcome measures

Outcome measures
Measure
AZD2171 45 mg
n=51 Participants
AZD2171 45mg/Day
Placebo
n=17 Participants
Placebo/Day
Best Percentage Change From Baseline in Tumour Size During the Study
-26.90 Percentage change from baseline
Standard Deviation 23.153
1.09 Percentage change from baseline
Standard Deviation 26.783

SECONDARY outcome

Timeframe: Treatment period up to 2nd data cut-off of 8th March 2009

Population: For patients to be included in the analysis they had to have been evaluable for RECIST and have been a responder (Complete response (CR) or Partial Response (PR)). 13 of the 19 responders had not progressed by the data cut off so their responses are ongoing and are censored at the date of the last evaluable visit before the data cut-off.

Based on RECIST measurements taken throughout the study and best objective tumour response at the defined analysis cut-off point. Measured from the time the criteria for complete response (CR)/partial response (PR) are first met (whichever is recorded first) until the patient progresses or dies.

Outcome measures

Outcome measures
Measure
AZD2171 45 mg
n=18 Participants
AZD2171 45mg/Day
Placebo
n=1 Participants
Placebo/Day
Duration of Response
18.595 Months
Interval 12.517 to 18.595
11.1 Months
Interval 11.1 to 11.1

SECONDARY outcome

Timeframe: Treatment period up to 2nd data cut-off of 8th March 2009.

Population: Comparison of PFS between patients randomised to cediranib 45 mg versus those randomised to placebo. All patients irrespective of whether they had a 12 week scan are included in this analysis. At week 12 placebo patients were able to switch to cediranib.

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

Outcome measures
Measure
AZD2171 45 mg
n=53 Participants
AZD2171 45mg/Day
Placebo
n=18 Participants
Placebo/Day
Progression Free Survival
12.1 Months
Interval 0.0 to 21.6
2.76 Months
Interval 0.0 to 21.5

SECONDARY outcome

Timeframe: Response rate at 12 weeks was based on RECIST measurements taken at baseline and at Week 12, or upon progression if this was before Week 12.

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. At 12 weeks, tumour responses would be unconfirmed, as this was the first post-baseline RECIST assessment, unless a patient had a RECIST assessment before Week 12 to confirm a suspected progression.

Outcome measures

Outcome measures
Measure
AZD2171 45 mg
n=53 Participants
AZD2171 45mg/Day
Placebo
n=18 Participants
Placebo/Day
Objective Tumour Response at 12 Weeks
11 Participants
0 Participants

SECONDARY outcome

Timeframe: Baseline, Week 12 and every 8 weeks thereafter or until progression.

Population: For the patients who switched from placebo to cediranib after unblinding, the baseline RECIST assessment was not reset to their last scan placebo, owing to the methods of data collection; therefore, it was not possible to determine their subsequent response to cediranib treatment using a 'best response' summary.

Best Objective Tumour response as defined by RECIST. Patients were assigned to 1 of the following best objective tumour response categories: complete response (CR) defined as a Disappearance of all target lesions, partial response (PR), defined as At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum LD, stable disease (SD) defined as Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD since the treatment started, or progressive disease (PD) defined as At least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded (either at baseline or at previous assessment since treatment began). Patients who were evaluable for RECIST assessments, but who did not meet the criteria for CR, PR, SD, or PD, were assigned to the response category of not evaluable (NE).

Outcome measures

Outcome measures
Measure
AZD2171 45 mg
n=53 Participants
AZD2171 45mg/Day
Placebo
n=18 Participants
Placebo/Day
Best Objective Tumour Response
18 Participants
1 Participants

Adverse Events

Cediranib DB

Serious events: 10 serious events
Other events: 53 other events
Deaths: 0 deaths

Placebo DB

Serious events: 3 serious events
Other events: 16 other events
Deaths: 0 deaths

Cediranib OL

Serious events: 15 serious events
Other events: 57 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Cediranib DB
n=53 participants at risk
Double Blind part
Placebo DB
n=18 participants at risk
Double Blind part
Cediranib OL
n=58 participants at risk
Open Label part
Cardiac disorders
Atrial Fibrillation
1.9%
1/53
0.00%
0/18
0.00%
0/58
Gastrointestinal disorders
Abdominal Pain
1.9%
1/53
0.00%
0/18
3.4%
2/58
Gastrointestinal disorders
Diarrhoea
0.00%
0/53
0.00%
0/18
3.4%
2/58
Gastrointestinal disorders
Abdominal Pain Upper
0.00%
0/53
0.00%
0/18
1.7%
1/58
Gastrointestinal disorders
Gastric Ulcer Haemorrhage
0.00%
0/53
0.00%
0/18
1.7%
1/58
Gastrointestinal disorders
Gastrointestinal Haemorrhage
1.9%
1/53
0.00%
0/18
0.00%
0/58
Gastrointestinal disorders
Nausea
1.9%
1/53
0.00%
0/18
1.7%
1/58
Gastrointestinal disorders
Vomiting
1.9%
1/53
0.00%
0/18
1.7%
1/58
General disorders
Fatigue
1.9%
1/53
0.00%
0/18
0.00%
0/58
Hepatobiliary disorders
Hepatic Function Abnormal
1.9%
1/53
0.00%
0/18
0.00%
0/58
Hepatobiliary disorders
Jaundice Cholestatic
0.00%
0/53
5.6%
1/18
0.00%
0/58
Infections and infestations
Lower Respiratory Tract Infection
0.00%
0/53
0.00%
0/18
1.7%
1/58
Infections and infestations
Pneumonia
1.9%
1/53
0.00%
0/18
0.00%
0/58
Infections and infestations
Urinary Tract Infection
1.9%
1/53
0.00%
0/18
0.00%
0/58
Injury, poisoning and procedural complications
Clavicle Fracture
0.00%
0/53
0.00%
0/18
1.7%
1/58
Injury, poisoning and procedural complications
Lower Limb Fracture
0.00%
0/53
0.00%
0/18
1.7%
1/58
Investigations
Blood Calcium Increased
0.00%
0/53
0.00%
0/18
1.7%
1/58
Metabolism and nutrition disorders
Dehydration
0.00%
0/53
0.00%
0/18
3.4%
2/58
Metabolism and nutrition disorders
Hypercalcaemia
0.00%
0/53
5.6%
1/18
0.00%
0/58
Musculoskeletal and connective tissue disorders
Back Pain
1.9%
1/53
0.00%
0/18
0.00%
0/58
Musculoskeletal and connective tissue disorders
Bursitis
0.00%
0/53
0.00%
0/18
1.7%
1/58
Musculoskeletal and connective tissue disorders
Muscular Weakness
0.00%
0/53
0.00%
0/18
1.7%
1/58
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain
1.9%
1/53
0.00%
0/18
0.00%
0/58
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intracranial Tumour Haemorrhage
1.9%
1/53
0.00%
0/18
0.00%
0/58
Nervous system disorders
Cerebral Infarction
0.00%
0/53
0.00%
0/18
1.7%
1/58
Nervous system disorders
Coma
1.9%
1/53
0.00%
0/18
0.00%
0/58
Nervous system disorders
Headache
0.00%
0/53
0.00%
0/18
1.7%
1/58
Nervous system disorders
Loss Of Consciousness
1.9%
1/53
0.00%
0/18
0.00%
0/58
Nervous system disorders
Reversible Posterior Leukoencephalopathy Syndrome
1.9%
1/53
5.6%
1/18
1.7%
1/58
Psychiatric disorders
Agitation
0.00%
0/53
0.00%
0/18
1.7%
1/58
Psychiatric disorders
Confusional State
0.00%
0/53
0.00%
0/18
1.7%
1/58
Renal and urinary disorders
Haematuria
0.00%
0/53
0.00%
0/18
1.7%
1/58
Renal and urinary disorders
Proteinuria
0.00%
0/53
0.00%
0/18
1.7%
1/58
Renal and urinary disorders
Renal Failure Acute
0.00%
0/53
0.00%
0/18
1.7%
1/58
Reproductive system and breast disorders
Bartholin's Cyst
0.00%
0/53
0.00%
0/18
1.7%
1/58
Respiratory, thoracic and mediastinal disorders
Dyspnoea
0.00%
0/53
5.6%
1/18
3.4%
2/58
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
1.9%
1/53
0.00%
0/18
0.00%
0/58
Skin and subcutaneous tissue disorders
Dermatitis Bullous
1.9%
1/53
0.00%
0/18
0.00%
0/58
Vascular disorders
Hypertension
1.9%
1/53
0.00%
0/18
0.00%
0/58
Vascular disorders
Orthostatic Hypotension
0.00%
0/53
0.00%
0/18
1.7%
1/58

Other adverse events

Other adverse events
Measure
Cediranib DB
n=53 participants at risk
Double Blind part
Placebo DB
n=18 participants at risk
Double Blind part
Cediranib OL
n=58 participants at risk
Open Label part
Cardiac disorders
Splinter Haemorrhages
5.7%
3/53
0.00%
0/18
1.7%
1/58
Ear and labyrinth disorders
Tinnitus
5.7%
3/53
0.00%
0/18
3.4%
2/58
Endocrine disorders
Hypothyroidism
7.5%
4/53
0.00%
0/18
5.2%
3/58
Gastrointestinal disorders
Diarrhoea
73.6%
39/53
27.8%
5/18
60.3%
35/58
Gastrointestinal disorders
Nausea
32.1%
17/53
27.8%
5/18
44.8%
26/58
Gastrointestinal disorders
Constipation
30.2%
16/53
22.2%
4/18
17.2%
10/58
Gastrointestinal disorders
Stomatitis
30.2%
16/53
11.1%
2/18
22.4%
13/58
Gastrointestinal disorders
Vomiting
17.0%
9/53
22.2%
4/18
22.4%
13/58
Gastrointestinal disorders
Abdominal Pain
13.2%
7/53
11.1%
2/18
15.5%
9/58
Gastrointestinal disorders
Dyspepsia
9.4%
5/53
16.7%
3/18
12.1%
7/58
Gastrointestinal disorders
Abdominal Pain Upper
7.5%
4/53
0.00%
0/18
5.2%
3/58
Gastrointestinal disorders
Dry Mouth
5.7%
3/53
0.00%
0/18
5.2%
3/58
Gastrointestinal disorders
Flatulence
0.00%
0/53
0.00%
0/18
5.2%
3/58
Gastrointestinal disorders
Glossodynia
5.7%
3/53
0.00%
0/18
0.00%
0/58
Gastrointestinal disorders
Haemorrhoids
1.9%
1/53
0.00%
0/18
5.2%
3/58
Gastrointestinal disorders
Oral Pain
5.7%
3/53
0.00%
0/18
5.2%
3/58
Gastrointestinal disorders
Toothache
5.7%
3/53
0.00%
0/18
3.4%
2/58
Gastrointestinal disorders
Abdominal Distension
0.00%
0/53
5.6%
1/18
1.7%
1/58
Gastrointestinal disorders
Gastrooesophageal Reflux Disease
0.00%
0/53
5.6%
1/18
0.00%
0/58
General disorders
Fatigue
58.5%
31/53
50.0%
9/18
43.1%
25/58
General disorders
Feeling Cold
9.4%
5/53
0.00%
0/18
0.00%
0/58
General disorders
Oedema Peripheral
9.4%
5/53
11.1%
2/18
6.9%
4/58
General disorders
Chills
5.7%
3/53
0.00%
0/18
1.7%
1/58
General disorders
Non-Cardiac Chest Pain
0.00%
0/53
0.00%
0/18
5.2%
3/58
General disorders
Pyrexia
0.00%
0/53
5.6%
1/18
3.4%
2/58
Hepatobiliary disorders
Jaundice
0.00%
0/53
5.6%
1/18
0.00%
0/58
Infections and infestations
Nasopharyngitis
7.5%
4/53
5.6%
1/18
19.0%
11/58
Infections and infestations
Upper Respiratory Tract Infection
3.8%
2/53
0.00%
0/18
8.6%
5/58
Infections and infestations
Lower Respiratory Tract Infection
7.5%
4/53
11.1%
2/18
6.9%
4/58
Infections and infestations
Sinusitis
0.00%
0/53
0.00%
0/18
5.2%
3/58
Infections and infestations
Urinary Tract Infection
1.9%
1/53
0.00%
0/18
5.2%
3/58
Infections and infestations
Oral Candidiasis
0.00%
0/53
5.6%
1/18
3.4%
2/58
Infections and infestations
Influenza
0.00%
0/53
5.6%
1/18
1.7%
1/58
Infections and infestations
Oral Herpes
0.00%
0/53
5.6%
1/18
1.7%
1/58
Injury, poisoning and procedural complications
Arthropod Bite
0.00%
0/53
5.6%
1/18
0.00%
0/58
Injury, poisoning and procedural complications
Procedural Pain
1.9%
1/53
5.6%
1/18
1.7%
1/58
Injury, poisoning and procedural complications
Sunburn
0.00%
0/53
5.6%
1/18
0.00%
0/58
Investigations
Weight Decreased
11.3%
6/53
5.6%
1/18
25.9%
15/58
Metabolism and nutrition disorders
Anorexia
24.5%
13/53
0.00%
0/18
19.0%
11/58
Metabolism and nutrition disorders
Decreased Appetite
17.0%
9/53
0.00%
0/18
19.0%
11/58
Metabolism and nutrition disorders
Appetite Disorder
0.00%
0/53
5.6%
1/18
0.00%
0/58
Musculoskeletal and connective tissue disorders
Back Pain
11.3%
6/53
22.2%
4/18
13.8%
8/58
Musculoskeletal and connective tissue disorders
Pain In Extremity
5.7%
3/53
5.6%
1/18
13.8%
8/58
Musculoskeletal and connective tissue disorders
Myalgia
11.3%
6/53
0.00%
0/18
6.9%
4/58
Musculoskeletal and connective tissue disorders
Arthralgia
9.4%
5/53
11.1%
2/18
6.9%
4/58
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
9.4%
5/53
5.6%
1/18
6.9%
4/58
Musculoskeletal and connective tissue disorders
Muscle Spasms
7.5%
4/53
5.6%
1/18
6.9%
4/58
Musculoskeletal and connective tissue disorders
Muscular Weakness
7.5%
4/53
0.00%
0/18
3.4%
2/58
Musculoskeletal and connective tissue disorders
Bone Pain
3.8%
2/53
0.00%
0/18
5.2%
3/58
Musculoskeletal and connective tissue disorders
Flank Pain
0.00%
0/53
16.7%
3/18
5.2%
3/58
Musculoskeletal and connective tissue disorders
Joint Stiffness
5.7%
3/53
0.00%
0/18
3.4%
2/58
Musculoskeletal and connective tissue disorders
Joint Swelling
5.7%
3/53
0.00%
0/18
1.7%
1/58
Musculoskeletal and connective tissue disorders
Musculoskeletal Stiffness
5.7%
3/53
0.00%
0/18
5.2%
3/58
Musculoskeletal and connective tissue disorders
Neck Pain
5.7%
3/53
5.6%
1/18
3.4%
2/58
Musculoskeletal and connective tissue disorders
Groin Pain
0.00%
0/53
5.6%
1/18
1.7%
1/58
Musculoskeletal and connective tissue disorders
Myopathy
1.9%
1/53
5.6%
1/18
0.00%
0/58
Nervous system disorders
Headache
45.3%
24/53
22.2%
4/18
17.2%
10/58
Nervous system disorders
Dizziness
15.1%
8/53
0.00%
0/18
10.3%
6/58
Nervous system disorders
Lethargy
13.2%
7/53
5.6%
1/18
3.4%
2/58
Nervous system disorders
Dysgeusia
9.4%
5/53
0.00%
0/18
6.9%
4/58
Nervous system disorders
Paraesthesia
1.9%
1/53
5.6%
1/18
6.9%
4/58
Nervous system disorders
Dyskinesia
0.00%
0/53
5.6%
1/18
0.00%
0/58
Nervous system disorders
Somnolence
0.00%
0/53
5.6%
1/18
0.00%
0/58
Psychiatric disorders
Insomnia
11.3%
6/53
0.00%
0/18
6.9%
4/58
Psychiatric disorders
Depression
1.9%
1/53
0.00%
0/18
8.6%
5/58
Psychiatric disorders
Anxiety
3.8%
2/53
5.6%
1/18
0.00%
0/58
Psychiatric disorders
Confusional State
3.8%
2/53
5.6%
1/18
3.4%
2/58
Renal and urinary disorders
Proteinuria
7.5%
4/53
0.00%
0/18
1.7%
1/58
Renal and urinary disorders
Dysuria
0.00%
0/53
5.6%
1/18
0.00%
0/58
Renal and urinary disorders
Renal Failure
0.00%
0/53
5.6%
1/18
0.00%
0/58
Respiratory, thoracic and mediastinal disorders
Dysphonia
58.5%
31/53
5.6%
1/18
31.0%
18/58
Respiratory, thoracic and mediastinal disorders
Dyspnoea
13.2%
7/53
11.1%
2/18
17.2%
10/58
Respiratory, thoracic and mediastinal disorders
Cough
7.5%
4/53
16.7%
3/18
10.3%
6/58
Respiratory, thoracic and mediastinal disorders
Epistaxis
7.5%
4/53
0.00%
0/18
5.2%
3/58
Respiratory, thoracic and mediastinal disorders
Haemoptysis
7.5%
4/53
0.00%
0/18
1.7%
1/58
Respiratory, thoracic and mediastinal disorders
Rales
3.8%
2/53
16.7%
3/18
3.4%
2/58
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
3.8%
2/53
11.1%
2/18
3.4%
2/58
Respiratory, thoracic and mediastinal disorders
Productive Cough
1.9%
1/53
5.6%
1/18
3.4%
2/58
Skin and subcutaneous tissue disorders
Palmar-Plantar Erythrodysaesthesia Syndrome
20.8%
11/53
0.00%
0/18
20.7%
12/58
Skin and subcutaneous tissue disorders
Rash
18.9%
10/53
11.1%
2/18
13.8%
8/58
Skin and subcutaneous tissue disorders
Alopecia
5.7%
3/53
5.6%
1/18
12.1%
7/58
Skin and subcutaneous tissue disorders
Dry Skin
7.5%
4/53
0.00%
0/18
3.4%
2/58
Skin and subcutaneous tissue disorders
Erythema
1.9%
1/53
0.00%
0/18
6.9%
4/58
Skin and subcutaneous tissue disorders
Hyperkeratosis
0.00%
0/53
0.00%
0/18
5.2%
3/58
Skin and subcutaneous tissue disorders
Rash Erythematous
5.7%
3/53
0.00%
0/18
0.00%
0/58
Skin and subcutaneous tissue disorders
Rash Macular
1.9%
1/53
11.1%
2/18
5.2%
3/58
Skin and subcutaneous tissue disorders
Pruritus
3.8%
2/53
5.6%
1/18
1.7%
1/58
Skin and subcutaneous tissue disorders
Actinic Keratosis
0.00%
0/53
5.6%
1/18
0.00%
0/58
Skin and subcutaneous tissue disorders
Cold Sweat
0.00%
0/53
5.6%
1/18
0.00%
0/58
Vascular disorders
Hypertension
64.2%
34/53
22.2%
4/18
12.1%
7/58
Vascular disorders
Flushing
5.7%
3/53
5.6%
1/18
1.7%
1/58
Vascular disorders
Hypotension
0.00%
0/53
0.00%
0/18
5.2%
3/58

Additional Information

Gerard Lynch

AstraZeneca

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