AZD2171 in Addition to Fulvestrant in Patients With Advanced Breast Cancer.

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00454805
• Collaborator: (none)
• Enrollment: 75
• Locations: 16
• Arms: 2
• Duration (Months): 109
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether AZD2171 can effectively improve time to tumour progression when added to fulvestrant in patients with advanced hormone sensitive breast cancer who progressed on prior hormonal therapy.

Condition or Disease	Intervention/Treatment	Phase
Advanced Breast Cancer	Drug: AZD2171; Drug: Fulvestrant	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 75 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase II, Double-Blind, Placebo Controlled, Randomized Study to Assess the Efficacy and Safety of AZD2171 in Combination With Fulvestrant vs Fulvestrant Alone in Hormone Sensitive (ER+ve or PgR+ve) Post Menopausal Metastatic Breast Cancer Patients
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Apr 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 2 Fulvestrant Monotherapy	Drug: Fulvestrant; intramuscular injection; Other Names: Faslodex ZD9238
Experimental: 3 AZD2171 + Fulvestrant	Drug: AZD2171; Oral tablet; Other Names: Recentin ; Drug: Fulvestrant; intramuscular injection; Other Names: Faslodex ZD9238

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival [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.

Secondary Outcome Measures

1. Objective Response Rate [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

2. Duration of Response [Every 8 weeks until progression or discontinuation]

   Number of days from date of response (complete/partial based on RECIST) to date of progression

3. Clinical Benefit Rate [Every 8 weeks until progression or discontinuation]

   Clinical 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.

4. Duration of Clinical Benefit [Every 8 weeks until progression or discontinuation]

   Number 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 130 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Written informed consent

• Females with histological/cytological confirmation of hormone sensitive breast cancer with evidence of metastatic disease

• One or more evaluable lesions

Exclusion Criteria:

• Prior hormonal therapy with fulvestrant

• More than one course of prior systemic cytotoxic chemotherapy for metastatic breast cancer

• Prior biologic therapy for ABC including Anti-VEGF agents

• Radiation therapy within 4 weeks prior to provision of consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Burbank	California	United States
2	Research Site	Los Angeles	California	United States
3	Research Site	Palm Springs	California	United States
4	Research Site	Boca Raton	Florida	United States
5	Research Site	Honolulu	Hawaii	United States
6	Research Site	New York	New York	United States
7	Research Site	Fitzroy		Australia
8	Research Site	Parkville		Australia
9	Research Site	Perth		Australia
10	Research Site	Waratah		Australia
11	Research Site	Belo Horizonte		Brazil
12	Research Site	Curitiba		Brazil
13	Research Site	Fortaleza		Brazil
14	Research Site	Porto Alegre		Brazil
15	Research Site	Santro Andre		Brazil
16	Research Site	São Paulo		Brazil

Sponsors and Collaborators

• AstraZeneca

Investigators

• Study Director: Bijoyesh Mookerjee, MD, AstraZeneca

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• CSR-D8480C00007.pdf

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00454805
• Other Study ID Numbers: D8480C00007
• First Posted: Apr 2, 2007
• Last Update Posted: Aug 3, 2016
• Last Verified: Jul 1, 2016

• Keywords provided by AstraZeneca: Advanced Breast Cancer
• Additional relevant MeSH terms: Breast Neoplasms; Fulvestrant; Cediranib

Study Results

Participant Flow

Recruitment Details	Randomised=ITT=Safety: Cediranib 31, Placebo 31
Pre-assignment Detail	In this study, 75 patients were enrolled and 62 randomised.

Arm/Group Title	Cediranib 45 mg	Placebo
Arm/Group Description	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+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)
Period Title: Overall Study
STARTED	31	31
COMPLETED	5	8
NOT COMPLETED	26	23

Baseline Characteristics

Arm/Group Title	Cediranib 45 mg	Placebo	Total
Arm/Group Description	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+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 of all reporting groups
Overall Participants	31	31	62
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60.4 (11.4)	57.9 (9.7)	59.1 (10.6)
Sex: Female, Male (Count of Participants)
Female	31 100%	31 100%	62 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival
Description	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.
Time Frame	RECIST performed at screening and every 8 weeks through to progression or discontinuation whichever is earliest.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cediranib 45 mg	Placebo
Arm/Group Description	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+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)
Measure Participants	31	31
Median (95% Confidence Interval) [Days]	223	112

2. Secondary Outcome

Title	Objective Response Rate
Description	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
Time Frame	RECIST performed at screening and every 8 weeks through to progression or discontinuation whichever is earliest.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cediranib 45 mg	Placebo
Arm/Group Description	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+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)
Measure Participants	18	12
Number [Participants]	4 12.9%	1 3.2%

3. Secondary Outcome

Title	Duration of Response
Description	Number of days from date of response (complete/partial based on RECIST) to date of progression
Time Frame	Every 8 weeks until progression or discontinuation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cediranib 45 mg	Placebo
Arm/Group Description	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+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)
Measure Participants	31	31
Median (Full Range) [Days]	207.5	224.0

4. Secondary Outcome

Title	Clinical Benefit Rate
Description	Clinical 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.
Time Frame	Every 8 weeks until progression or discontinuation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cediranib 45 mg	Placebo
Arm/Group Description	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+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)
Measure Participants	31	31
Number [Ratio]	0.419	0.419

5. Secondary Outcome

Title	Duration of Clinical Benefit
Description	Number 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.
Time Frame	Every 8 weeks until progression or discontinuation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cediranib 45 mg	Placebo
Arm/Group Description	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+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)
Measure Participants	13	13
Mean (Standard Deviation) [Days]	306.6 (104.2)	343.8 (115.8)

Adverse Events

Arm/Group Title	Cediranib 45 mg		Placebo
Arm/Group Description	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+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)
All Cause Mortality
	Cediranib 45 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cediranib 45 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/31 (48.4%)		4/31 (12.9%)
Cardiac disorders
Intracardiac Thrombus	1/31 (3.2%)		0/31 (0%)
Gastrointestinal disorders
Diarrhoea	2/31 (6.5%)		0/31 (0%)
Nausea	2/31 (6.5%)		0/31 (0%)
Vomiting	2/31 (6.5%)		0/31 (0%)
Ascites	0/31 (0%)		1/31 (3.2%)
Ileus	1/31 (3.2%)		0/31 (0%)
Small Intestinal Obstruction	1/31 (3.2%)		0/31 (0%)
General disorders
Multi-Organ Failure	0/31 (0%)		1/31 (3.2%)
Infections and infestations
Sepsis	1/31 (3.2%)		0/31 (0%)
Weight Decreased	1/31 (3.2%)		0/31 (0%)
Metabolism and nutrition disorders
Dehydration	2/31 (6.5%)		0/31 (0%)
Hypokalaemia	0/31 (0%)		1/31 (3.2%)
Water Intoxication	1/31 (3.2%)		0/31 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/31 (6.5%)		0/31 (0%)
Pain In Extremity	2/31 (6.5%)		1/31 (3.2%)
Nervous system disorders
Convulsion	3/31 (9.7%)		0/31 (0%)
Headache	1/31 (3.2%)		0/31 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/31 (0%)		1/31 (3.2%)
Haemoptysis	1/31 (3.2%)		0/31 (0%)
Respiratory Failure	0/31 (0%)		1/31 (3.2%)
Vascular disorders
Hypertension	4/31 (12.9%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	Cediranib 45 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/31 (93.5%)		30/31 (96.8%)
Endocrine disorders
Hypothyroidism	4/31 (12.9%)		0/31 (0%)
Gastrointestinal disorders
Diarrhoea	20/31 (64.5%)		4/31 (12.9%)
Constipation	11/31 (35.5%)		4/31 (12.9%)
Stomatitis	11/31 (35.5%)		3/31 (9.7%)
Vomiting	11/31 (35.5%)		3/31 (9.7%)
Nausea	10/31 (32.3%)		8/31 (25.8%)
Abdominal Pain	6/31 (19.4%)		3/31 (9.7%)
Dyspepsia	4/31 (12.9%)		0/31 (0%)
Abdominal Pain Upper	3/31 (9.7%)		2/31 (6.5%)
Dry Mouth	2/31 (6.5%)		3/31 (9.7%)
Oral Pain	3/31 (9.7%)		0/31 (0%)
Dysphagia	2/31 (6.5%)		2/31 (6.5%)
Gastrooesophageal Reflux Disease	2/31 (6.5%)		1/31 (3.2%)
Gingival Bleeding	2/31 (6.5%)		1/31 (3.2%)
Toothache	2/31 (6.5%)		0/31 (0%)
General disorders
Fatigue	19/31 (61.3%)		8/31 (25.8%)
Asthenia	6/31 (19.4%)		0/31 (0%)
Oedema Peripheral	3/31 (9.7%)		3/31 (9.7%)
Pyrexia	3/31 (9.7%)		2/31 (6.5%)
Chills	2/31 (6.5%)		1/31 (3.2%)
Injection Site Pain	1/31 (3.2%)		2/31 (6.5%)
Non-Cardiac Chest Pain	2/31 (6.5%)		0/31 (0%)
Pain	2/31 (6.5%)		1/31 (3.2%)
Infections and infestations
Urinary Tract Infection	4/31 (12.9%)		2/31 (6.5%)
Nasopharyngitis	1/31 (3.2%)		3/31 (9.7%)
Upper Respiratory Tract Infection	3/31 (9.7%)		2/31 (6.5%)
Weight Decreased	6/31 (19.4%)		0/31 (0%)
Weight Increased	0/31 (0%)		3/31 (9.7%)
Metabolism and nutrition disorders
Anorexia	12/31 (38.7%)		2/31 (6.5%)
Decreased Appetite	2/31 (6.5%)		0/31 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	5/31 (16.1%)		8/31 (25.8%)
Arthralgia	6/31 (19.4%)		7/31 (22.6%)
Pain In Extremity	6/31 (19.4%)		5/31 (16.1%)
Bone Pain	3/31 (9.7%)		5/31 (16.1%)
Musculoskeletal Pain	5/31 (16.1%)		2/31 (6.5%)
Myalgia	4/31 (12.9%)		3/31 (9.7%)
Muscular Weakness	3/31 (9.7%)		0/31 (0%)
Musculoskeletal Chest Pain	3/31 (9.7%)		2/31 (6.5%)
Neck Pain	2/31 (6.5%)		2/31 (6.5%)
Nervous system disorders
Headache	11/31 (35.5%)		7/31 (22.6%)
Dizziness	5/31 (16.1%)		3/31 (9.7%)
Dysgeusia	5/31 (16.1%)		0/31 (0%)
Paraesthesia	1/31 (3.2%)		3/31 (9.7%)
Hypoaesthesia	0/31 (0%)		2/31 (6.5%)
Peripheral Sensory Neuropathy	0/31 (0%)		2/31 (6.5%)
Somnolence	2/31 (6.5%)		2/31 (6.5%)
Psychiatric disorders
Anxiety	1/31 (3.2%)		3/31 (9.7%)
Insomnia	1/31 (3.2%)		2/31 (6.5%)
Reproductive system and breast disorders
Breast Pain	1/31 (3.2%)		3/31 (9.7%)
Respiratory, thoracic and mediastinal disorders
Dysphonia	11/31 (35.5%)		0/31 (0%)
Cough	6/31 (19.4%)		4/31 (12.9%)
Epistaxis	4/31 (12.9%)		1/31 (3.2%)
Oropharyngeal Pain	4/31 (12.9%)		3/31 (9.7%)
Dyspnoea	3/31 (9.7%)		3/31 (9.7%)
Dry Throat	2/31 (6.5%)		1/31 (3.2%)
Skin and subcutaneous tissue disorders
Dry Skin	4/31 (12.9%)		0/31 (0%)
Erythema	3/31 (9.7%)		2/31 (6.5%)
Rash	2/31 (6.5%)		3/31 (9.7%)
Alopecia	1/31 (3.2%)		2/31 (6.5%)
Hyperkeratosis	2/31 (6.5%)		0/31 (0%)
Palmar-Plantar Erythrodysaesthesia Syndrome	2/31 (6.5%)		0/31 (0%)
Pruritus	1/31 (3.2%)		2/31 (6.5%)
Skin Hyperpigmentation	2/31 (6.5%)		0/31 (0%)
Vascular disorders
Hypertension	16/31 (51.6%)		6/31 (19.4%)
Hot Flush	3/31 (9.7%)		11/31 (35.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.