Trial Outcomes & Findings for AZD2171 in Addition to Fulvestrant in Patients With Advanced Breast Cancer. (NCT NCT00454805)
NCT ID: NCT00454805
Last Updated: 2016-08-03
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
PHASE2
Target enrollment
75 participants
Primary outcome timeframe
RECIST performed at screening and every 8 weeks through to progression or discontinuation whichever is earliest.
Results posted on
2016-08-03
Participant Flow
Randomised=ITT=Safety: Cediranib 31, Placebo 31
In this study, 75 patients were enrolled and 62 randomised.
Participant milestones
| Measure |
Cediranib 45 mg
Cediranib 45 mg+Fulvestrant 250 mg
Patients randomised to the investigational arm (fulvestrant + cediranib) received treatment according to the following schedule:
* Day 1: fulvestrant 500 mg im
* Day 15: fulvestrant 250 mg im
* Day 29, and every 28 days thereafter: fulvestrant 250 mg im
* and daily: cediranib 45 mg (administered orally)
|
Placebo
Placebo+Fulvestrant 250 mg
Patients randomised to the control arm (fulvestrant + placebo) received treatment according to the following schedule:
* Day 1: fulvestrant 500 mg im
* Day 15: fulvestrant 250 mg im
* Day 29, and every 28 days thereafter: fulvestrant 250 mg im
* and daily: placebo to match cediranib (administered orally)
|
|---|---|---|
|
Overall Study
STARTED
|
31
|
31
|
|
Overall Study
COMPLETED
|
5
|
8
|
|
Overall Study
NOT COMPLETED
|
26
|
23
|
Reasons for withdrawal
| Measure |
Cediranib 45 mg
Cediranib 45 mg+Fulvestrant 250 mg
Patients randomised to the investigational arm (fulvestrant + cediranib) received treatment according to the following schedule:
* Day 1: fulvestrant 500 mg im
* Day 15: fulvestrant 250 mg im
* Day 29, and every 28 days thereafter: fulvestrant 250 mg im
* and daily: cediranib 45 mg (administered orally)
|
Placebo
Placebo+Fulvestrant 250 mg
Patients randomised to the control arm (fulvestrant + placebo) received treatment according to the following schedule:
* Day 1: fulvestrant 500 mg im
* Day 15: fulvestrant 250 mg im
* Day 29, and every 28 days thereafter: fulvestrant 250 mg im
* and daily: placebo to match cediranib (administered orally)
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
9
|
2
|
|
Overall Study
Death
|
0
|
2
|
|
Overall Study
Disease progression
|
16
|
19
|
|
Overall Study
In order to begin radiotherapy
|
1
|
0
|
Baseline Characteristics
AZD2171 in Addition to Fulvestrant in Patients With Advanced Breast Cancer.
Baseline characteristics by cohort
| Measure |
Cediranib 45 mg
n=31 Participants
Cediranib 45 mg+Fulvestrant 250 mg
Patients randomised to the investigational arm (fulvestrant + cediranib) received treatment according to the following schedule:
* Day 1: fulvestrant 500 mg im
* Day 15: fulvestrant 250 mg im
* Day 29, and every 28 days thereafter: fulvestrant 250 mg im
* and daily: cediranib 45 mg (administered orally)
|
Placebo
n=31 Participants
Placebo+Fulvestrant 250 mg
Patients randomised to the control arm (fulvestrant + placebo) received treatment according to the following schedule:
* Day 1: fulvestrant 500 mg im
* Day 15: fulvestrant 250 mg im
* Day 29, and every 28 days thereafter: fulvestrant 250 mg im
* and daily: placebo to match cediranib (administered orally)
|
Total
n=62 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60.4 Years
STANDARD_DEVIATION 11.4 • n=93 Participants
|
57.9 Years
STANDARD_DEVIATION 9.7 • n=4 Participants
|
59.1 Years
STANDARD_DEVIATION 10.6 • n=27 Participants
|
|
Sex: Female, Male
Female
|
31 Participants
n=93 Participants
|
31 Participants
n=4 Participants
|
62 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: RECIST performed at screening and every 8 weeks through to progression or discontinuation whichever is earliest.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 45 mg
n=31 Participants
Cediranib 45 mg+Fulvestrant 250 mg
Patients randomised to the investigational arm (fulvestrant + cediranib) received treatment according to the following schedule:
* Day 1: fulvestrant 500 mg im
* Day 15: fulvestrant 250 mg im
* Day 29, and every 28 days thereafter: fulvestrant 250 mg im
* and daily: cediranib 45 mg (administered orally)
|
Placebo
n=31 Participants
Placebo+Fulvestrant 250 mg
Patients randomised to the control arm (fulvestrant + placebo) received treatment according to the following schedule:
* Day 1: fulvestrant 500 mg im
* Day 15: fulvestrant 250 mg im
* Day 29, and every 28 days thereafter: fulvestrant 250 mg im
* and daily: placebo to match cediranib (administered orally)
|
|---|---|---|
|
Progression Free Survival
|
223 Days
Interval 129.0 to 340.0
|
112 Days
Interval 59.0 to 329.0
|
SECONDARY outcome
Timeframe: RECIST performed at screening and every 8 weeks through to progression or discontinuation whichever is earliest.Best objective tumour response (based on Response Evaluation Criteria in Solid Tumours (RECIST)) during the study for patients with measurable disease. Best objective tumour response defined as: Complete Response (CR) Disappearance of all target lesions Partial response (PR) At least a 30% decrease in the sum of longest diameters (LDs) of target lesions, taking as reference the baseline sum of LDs. Progression (PD) At least a 20% increase in the sum of LDs of target lesions, taking as reference the smallest sum of LDs since treatment started (including the baseline sum of LDs) and at least 5 mm increase. Stable disease (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD
Outcome measures
| Measure |
Cediranib 45 mg
n=18 Participants
Cediranib 45 mg+Fulvestrant 250 mg
Patients randomised to the investigational arm (fulvestrant + cediranib) received treatment according to the following schedule:
* Day 1: fulvestrant 500 mg im
* Day 15: fulvestrant 250 mg im
* Day 29, and every 28 days thereafter: fulvestrant 250 mg im
* and daily: cediranib 45 mg (administered orally)
|
Placebo
n=12 Participants
Placebo+Fulvestrant 250 mg
Patients randomised to the control arm (fulvestrant + placebo) received treatment according to the following schedule:
* Day 1: fulvestrant 500 mg im
* Day 15: fulvestrant 250 mg im
* Day 29, and every 28 days thereafter: fulvestrant 250 mg im
* and daily: placebo to match cediranib (administered orally)
|
|---|---|---|
|
Objective Response Rate
|
4 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Every 8 weeks until progression or discontinuationNumber of days from date of response (complete/partial based on RECIST) to date of progression
Outcome measures
| Measure |
Cediranib 45 mg
n=31 Participants
Cediranib 45 mg+Fulvestrant 250 mg
Patients randomised to the investigational arm (fulvestrant + cediranib) received treatment according to the following schedule:
* Day 1: fulvestrant 500 mg im
* Day 15: fulvestrant 250 mg im
* Day 29, and every 28 days thereafter: fulvestrant 250 mg im
* and daily: cediranib 45 mg (administered orally)
|
Placebo
n=31 Participants
Placebo+Fulvestrant 250 mg
Patients randomised to the control arm (fulvestrant + placebo) received treatment according to the following schedule:
* Day 1: fulvestrant 500 mg im
* Day 15: fulvestrant 250 mg im
* Day 29, and every 28 days thereafter: fulvestrant 250 mg im
* and daily: placebo to match cediranib (administered orally)
|
|---|---|---|
|
Duration of Response
|
207.5 Days
Interval 82.0 to 396.0
|
224.0 Days
Interval 224.0 to 224.0
|
SECONDARY outcome
Timeframe: Every 8 weeks until progression or discontinuationClinical Benefit is defined as the number of patients having a best overall tumour response of CR/PR or SD for ≥6 months. The Clinical Benefit rate is defined as the number of responders divided by the number in the Intention-to-treat (ITT) analysis set: responder=overall best response of complete response (CR)/partial response (PR) or stable disease (SD) for at least 6 months (calculated from the date of randomisation) as defined by RECIST criteria at any point prior to the data cut-off.
Outcome measures
| Measure |
Cediranib 45 mg
n=31 Participants
Cediranib 45 mg+Fulvestrant 250 mg
Patients randomised to the investigational arm (fulvestrant + cediranib) received treatment according to the following schedule:
* Day 1: fulvestrant 500 mg im
* Day 15: fulvestrant 250 mg im
* Day 29, and every 28 days thereafter: fulvestrant 250 mg im
* and daily: cediranib 45 mg (administered orally)
|
Placebo
n=31 Participants
Placebo+Fulvestrant 250 mg
Patients randomised to the control arm (fulvestrant + placebo) received treatment according to the following schedule:
* Day 1: fulvestrant 500 mg im
* Day 15: fulvestrant 250 mg im
* Day 29, and every 28 days thereafter: fulvestrant 250 mg im
* and daily: placebo to match cediranib (administered orally)
|
|---|---|---|
|
Clinical Benefit Rate
|
0.419 Ratio
|
0.419 Ratio
|
SECONDARY outcome
Timeframe: Every 8 weeks until progression or discontinuationNumber of days from date of clinical benefit to date of progression. Clinical benefit is defined as having a best overall tumour response of CR/PR or SD for ≥6 months.
Outcome measures
| Measure |
Cediranib 45 mg
n=13 Participants
Cediranib 45 mg+Fulvestrant 250 mg
Patients randomised to the investigational arm (fulvestrant + cediranib) received treatment according to the following schedule:
* Day 1: fulvestrant 500 mg im
* Day 15: fulvestrant 250 mg im
* Day 29, and every 28 days thereafter: fulvestrant 250 mg im
* and daily: cediranib 45 mg (administered orally)
|
Placebo
n=13 Participants
Placebo+Fulvestrant 250 mg
Patients randomised to the control arm (fulvestrant + placebo) received treatment according to the following schedule:
* Day 1: fulvestrant 500 mg im
* Day 15: fulvestrant 250 mg im
* Day 29, and every 28 days thereafter: fulvestrant 250 mg im
* and daily: placebo to match cediranib (administered orally)
|
|---|---|---|
|
Duration of Clinical Benefit
|
306.6 Days
Standard Deviation 104.2
|
343.8 Days
Standard Deviation 115.8
|
Adverse Events
Cediranib 45 mg
Serious events: 15 serious events
Other events: 29 other events
Deaths: 0 deaths
Placebo
Serious events: 4 serious events
Other events: 30 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cediranib 45 mg
n=31 participants at risk
Cediranib 45 mg+Fulvestrant 250 mg
Patients randomised to the investigational arm (fulvestrant + cediranib) received treatment according to the following schedule:
* Day 1: fulvestrant 500 mg im
* Day 15: fulvestrant 250 mg im
* Day 29, and every 28 days thereafter: fulvestrant 250 mg im
* and daily: cediranib 45 mg (administered orally)
|
Placebo
n=31 participants at risk
Placebo+Fulvestrant 250 mg
Patients randomised to the control arm (fulvestrant + placebo) received treatment according to the following schedule:
* Day 1: fulvestrant 500 mg im
* Day 15: fulvestrant 250 mg im
* Day 29, and every 28 days thereafter: fulvestrant 250 mg im
* and daily: placebo to match cediranib (administered orally)
|
|---|---|---|
|
Cardiac disorders
Intracardiac Thrombus
|
3.2%
1/31
|
0.00%
0/31
|
|
Gastrointestinal disorders
Diarrhoea
|
6.5%
2/31
|
0.00%
0/31
|
|
Gastrointestinal disorders
Nausea
|
6.5%
2/31
|
0.00%
0/31
|
|
Gastrointestinal disorders
Vomiting
|
6.5%
2/31
|
0.00%
0/31
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/31
|
3.2%
1/31
|
|
Gastrointestinal disorders
Ileus
|
3.2%
1/31
|
0.00%
0/31
|
|
Gastrointestinal disorders
Small Intestinal Obstruction
|
3.2%
1/31
|
0.00%
0/31
|
|
General disorders
Multi-Organ Failure
|
0.00%
0/31
|
3.2%
1/31
|
|
Infections and infestations
Sepsis
|
3.2%
1/31
|
0.00%
0/31
|
|
Infections and infestations
Weight Decreased
|
3.2%
1/31
|
0.00%
0/31
|
|
Metabolism and nutrition disorders
Dehydration
|
6.5%
2/31
|
0.00%
0/31
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/31
|
3.2%
1/31
|
|
Metabolism and nutrition disorders
Water Intoxication
|
3.2%
1/31
|
0.00%
0/31
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.5%
2/31
|
0.00%
0/31
|
|
Musculoskeletal and connective tissue disorders
Pain In Extremity
|
6.5%
2/31
|
3.2%
1/31
|
|
Nervous system disorders
Convulsion
|
9.7%
3/31
|
0.00%
0/31
|
|
Nervous system disorders
Headache
|
3.2%
1/31
|
0.00%
0/31
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/31
|
3.2%
1/31
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
3.2%
1/31
|
0.00%
0/31
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
0.00%
0/31
|
3.2%
1/31
|
|
Vascular disorders
Hypertension
|
12.9%
4/31
|
0.00%
0/31
|
Other adverse events
| Measure |
Cediranib 45 mg
n=31 participants at risk
Cediranib 45 mg+Fulvestrant 250 mg
Patients randomised to the investigational arm (fulvestrant + cediranib) received treatment according to the following schedule:
* Day 1: fulvestrant 500 mg im
* Day 15: fulvestrant 250 mg im
* Day 29, and every 28 days thereafter: fulvestrant 250 mg im
* and daily: cediranib 45 mg (administered orally)
|
Placebo
n=31 participants at risk
Placebo+Fulvestrant 250 mg
Patients randomised to the control arm (fulvestrant + placebo) received treatment according to the following schedule:
* Day 1: fulvestrant 500 mg im
* Day 15: fulvestrant 250 mg im
* Day 29, and every 28 days thereafter: fulvestrant 250 mg im
* and daily: placebo to match cediranib (administered orally)
|
|---|---|---|
|
Endocrine disorders
Hypothyroidism
|
12.9%
4/31
|
0.00%
0/31
|
|
Gastrointestinal disorders
Diarrhoea
|
64.5%
20/31
|
12.9%
4/31
|
|
Gastrointestinal disorders
Constipation
|
35.5%
11/31
|
12.9%
4/31
|
|
Gastrointestinal disorders
Stomatitis
|
35.5%
11/31
|
9.7%
3/31
|
|
Gastrointestinal disorders
Vomiting
|
35.5%
11/31
|
9.7%
3/31
|
|
Gastrointestinal disorders
Nausea
|
32.3%
10/31
|
25.8%
8/31
|
|
Gastrointestinal disorders
Abdominal Pain
|
19.4%
6/31
|
9.7%
3/31
|
|
Gastrointestinal disorders
Dyspepsia
|
12.9%
4/31
|
0.00%
0/31
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
9.7%
3/31
|
6.5%
2/31
|
|
Gastrointestinal disorders
Dry Mouth
|
6.5%
2/31
|
9.7%
3/31
|
|
Gastrointestinal disorders
Oral Pain
|
9.7%
3/31
|
0.00%
0/31
|
|
Gastrointestinal disorders
Dysphagia
|
6.5%
2/31
|
6.5%
2/31
|
|
Gastrointestinal disorders
Gastrooesophageal Reflux Disease
|
6.5%
2/31
|
3.2%
1/31
|
|
Gastrointestinal disorders
Gingival Bleeding
|
6.5%
2/31
|
3.2%
1/31
|
|
Gastrointestinal disorders
Toothache
|
6.5%
2/31
|
0.00%
0/31
|
|
General disorders
Fatigue
|
61.3%
19/31
|
25.8%
8/31
|
|
General disorders
Asthenia
|
19.4%
6/31
|
0.00%
0/31
|
|
General disorders
Oedema Peripheral
|
9.7%
3/31
|
9.7%
3/31
|
|
General disorders
Pyrexia
|
9.7%
3/31
|
6.5%
2/31
|
|
General disorders
Chills
|
6.5%
2/31
|
3.2%
1/31
|
|
General disorders
Injection Site Pain
|
3.2%
1/31
|
6.5%
2/31
|
|
General disorders
Non-Cardiac Chest Pain
|
6.5%
2/31
|
0.00%
0/31
|
|
General disorders
Pain
|
6.5%
2/31
|
3.2%
1/31
|
|
Infections and infestations
Urinary Tract Infection
|
12.9%
4/31
|
6.5%
2/31
|
|
Infections and infestations
Nasopharyngitis
|
3.2%
1/31
|
9.7%
3/31
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
9.7%
3/31
|
6.5%
2/31
|
|
Infections and infestations
Weight Decreased
|
19.4%
6/31
|
0.00%
0/31
|
|
Infections and infestations
Weight Increased
|
0.00%
0/31
|
9.7%
3/31
|
|
Metabolism and nutrition disorders
Anorexia
|
38.7%
12/31
|
6.5%
2/31
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
6.5%
2/31
|
0.00%
0/31
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
16.1%
5/31
|
25.8%
8/31
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
19.4%
6/31
|
22.6%
7/31
|
|
Musculoskeletal and connective tissue disorders
Pain In Extremity
|
19.4%
6/31
|
16.1%
5/31
|
|
Musculoskeletal and connective tissue disorders
Bone Pain
|
9.7%
3/31
|
16.1%
5/31
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
16.1%
5/31
|
6.5%
2/31
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
12.9%
4/31
|
9.7%
3/31
|
|
Musculoskeletal and connective tissue disorders
Muscular Weakness
|
9.7%
3/31
|
0.00%
0/31
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain
|
9.7%
3/31
|
6.5%
2/31
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
6.5%
2/31
|
6.5%
2/31
|
|
Nervous system disorders
Headache
|
35.5%
11/31
|
22.6%
7/31
|
|
Nervous system disorders
Dizziness
|
16.1%
5/31
|
9.7%
3/31
|
|
Nervous system disorders
Dysgeusia
|
16.1%
5/31
|
0.00%
0/31
|
|
Nervous system disorders
Paraesthesia
|
3.2%
1/31
|
9.7%
3/31
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/31
|
6.5%
2/31
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
0.00%
0/31
|
6.5%
2/31
|
|
Nervous system disorders
Somnolence
|
6.5%
2/31
|
6.5%
2/31
|
|
Psychiatric disorders
Anxiety
|
3.2%
1/31
|
9.7%
3/31
|
|
Psychiatric disorders
Insomnia
|
3.2%
1/31
|
6.5%
2/31
|
|
Reproductive system and breast disorders
Breast Pain
|
3.2%
1/31
|
9.7%
3/31
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
35.5%
11/31
|
0.00%
0/31
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
19.4%
6/31
|
12.9%
4/31
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
12.9%
4/31
|
3.2%
1/31
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
12.9%
4/31
|
9.7%
3/31
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
9.7%
3/31
|
9.7%
3/31
|
|
Respiratory, thoracic and mediastinal disorders
Dry Throat
|
6.5%
2/31
|
3.2%
1/31
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
12.9%
4/31
|
0.00%
0/31
|
|
Skin and subcutaneous tissue disorders
Erythema
|
9.7%
3/31
|
6.5%
2/31
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.5%
2/31
|
9.7%
3/31
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
3.2%
1/31
|
6.5%
2/31
|
|
Skin and subcutaneous tissue disorders
Hyperkeratosis
|
6.5%
2/31
|
0.00%
0/31
|
|
Skin and subcutaneous tissue disorders
Palmar-Plantar Erythrodysaesthesia Syndrome
|
6.5%
2/31
|
0.00%
0/31
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
3.2%
1/31
|
6.5%
2/31
|
|
Skin and subcutaneous tissue disorders
Skin Hyperpigmentation
|
6.5%
2/31
|
0.00%
0/31
|
|
Vascular disorders
Hypertension
|
51.6%
16/31
|
19.4%
6/31
|
|
Vascular disorders
Hot Flush
|
9.7%
3/31
|
35.5%
11/31
|
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