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

Study identifier:D8480C00007

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

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

Medical condition

Advanced breast cancer

Phase

Phase 2

Healthy volunteers

Study drug

AZD2171, Fulvestrant

Sex

Female

Actual Enrollment

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 01 Mar 2007

Primary Completion Date: 01 Dec 2008

Study Completion Date: 01 Apr 2016

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Jul 2016 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Waratah, Australia

Location

Research Site

Perth, Australia

Location

Research Site

Fitzroy, Australia

Location

Research Site

Parkville, Australia

Location

Research Site

São Paulo, Brazil

Location

Research Site

Fortaleza, Brazil

Location

Research Site

Porto Alegre, Brazil

Location

Research Site

Belo Horizonte, Brazil

Arms	Assigned Interventions
Active Comparator: 2 Fulvestrant Monotherapy	Drug: Fulvestrant intramuscular injection Other Name: Faslodex Other Name: ZD9238
Experimental: 3 AZD2171 + Fulvestrant	Drug: AZD2171 Oral tablet Other Name: Recentin Drug: Fulvestrant intramuscular injection Other Name: Faslodex Other Name: ZD9238

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Randomised=ITT=Safety: Cediranib 31, Placebo 31

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
In this study, 75 patients were enrolled and 62 randomised.

Reporting Groups

	Description
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)

Participant Flow: Overall Study

	Cediranib 45 mg	Placebo
STARTED	31^[1]	31^[2]
COMPLETED	5^[3]	8^[4]
NOT COMPLETED	26	23
Withdrawal by Subject	9	2
Death	0	2
Disease progression	16	19
In order to begin radiotherapy	1	0

[1]	Randomised
[2]	Randomised
[3]	Ongoing at data cut-off
[4]	Ongoing at data cut-off

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
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)

Baseline Measures

	Cediranib 45 mg	Placebo	Total
Number of Participants [units: Participants]	31	31	62
Age Continuous [units: Years] Mean ± Standard Deviation
Gender, Male/Female [units: ]
Female	31	31	62
Male	0	0	0

Outcome Measures

1. Primary Outcome Measure: Progression Free Survival [ Time Frame: RECIST performed at screening and every 8 weeks through to progression or discontinuation whichever is earliest. ]

Measure Type	Primary
Measure Name	Progression Free Survival
Measure 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.
Safety Issue?

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No text entered.

2. Secondary Outcome Measure: Objective Response Rate [ Time Frame: RECIST performed at screening and every 8 weeks through to progression or discontinuation whichever is earliest. ]

Measure Type	Secondary
Measure Name	Objective Response Rate
Measure 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.
Safety Issue?

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No text entered.

3. Secondary Outcome Measure: Duration of Response [ Time Frame: Every 8 weeks until progression or discontinuation ]

Measure Type	Secondary
Measure Name	Duration of Response
Measure 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
Safety Issue?

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No text entered.

4. Secondary Outcome Measure: Clinical Benefit Rate [ Time Frame: Every 8 weeks until progression or discontinuation ]

Measure Type	Secondary
Measure Name	Clinical Benefit Rate
Measure 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
Safety Issue?

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No text entered.

5. Secondary Outcome Measure: Duration of Clinical Benefit [ Time Frame: Every 8 weeks until progression or discontinuation ]

Measure Type	Secondary
Measure Name	Duration of Clinical Benefit
Measure 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
Safety Issue?

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No text entered.

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
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)

Serious Adverse Events

Cediranib 45 mg

Placebo

Total, serious adverse events

# participants affected / at risk

15/31 (48.39%)

4/31 (12.90%)

Cardiac disorders

Intracardiac Thrombus¹,^†

# participants affected / at risk

1/31 (3.23%)

0/31 (0.00%)

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

2/31 (6.45%)

0/31 (0.00%)

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

2/31 (6.45%)

0/31 (0.00%)

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

2/31 (6.45%)

0/31 (0.00%)

Gastrointestinal disorders

Ascites¹,^†

# participants affected / at risk

0/31 (0.00%)

1/31 (3.23%)

Gastrointestinal disorders

Ileus¹,^†

# participants affected / at risk

1/31 (3.23%)

0/31 (0.00%)

Gastrointestinal disorders

Small Intestinal Obstruction¹,^†

# participants affected / at risk

1/31 (3.23%)

0/31 (0.00%)

General disorders

Multi-Organ Failure¹,^†

# participants affected / at risk

0/31 (0.00%)

1/31 (3.23%)

Infections and infestations

Sepsis¹,^†

# participants affected / at risk

1/31 (3.23%)

0/31 (0.00%)

Infections and infestations

Weight Decreased¹,^†

# participants affected / at risk

1/31 (3.23%)

0/31 (0.00%)

Metabolism and nutrition disorders

Dehydration¹,^†

# participants affected / at risk

2/31 (6.45%)

0/31 (0.00%)

Metabolism and nutrition disorders

Hypokalaemia¹,^†

# participants affected / at risk

0/31 (0.00%)

1/31 (3.23%)

Metabolism and nutrition disorders

Water Intoxication¹,^†

# participants affected / at risk

1/31 (3.23%)

0/31 (0.00%)

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

2/31 (6.45%)

0/31 (0.00%)

Musculoskeletal and connective tissue disorders

Pain In Extremity¹,^†

# participants affected / at risk

2/31 (6.45%)

1/31 (3.23%)

Nervous system disorders

Convulsion¹,^†

# participants affected / at risk

3/31 (9.68%)

0/31 (0.00%)

Nervous system disorders

Headache¹,^†

# participants affected / at risk

1/31 (3.23%)

0/31 (0.00%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

0/31 (0.00%)

1/31 (3.23%)

Respiratory, thoracic and mediastinal disorders

Haemoptysis¹,^†

# participants affected / at risk

1/31 (3.23%)

0/31 (0.00%)

Respiratory, thoracic and mediastinal disorders

Respiratory Failure¹,^†

# participants affected / at risk

0/31 (0.00%)

1/31 (3.23%)

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

4/31 (12.90%)

0/31 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 11.1
2	Term from vocabulary,

Other Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
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)

Other Adverse Events

Cediranib 45 mg

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

29/31 (93.55%)

30/31 (96.77%)

Endocrine disorders

Hypothyroidism¹,^†

# participants affected / at risk

4/31 (12.90%)

0/31 (0.00%)

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

20/31 (64.52%)

4/31 (12.90%)

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

11/31 (35.48%)

4/31 (12.90%)

Gastrointestinal disorders

Stomatitis¹,^†

# participants affected / at risk

11/31 (35.48%)

3/31 (9.68%)

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

11/31 (35.48%)

3/31 (9.68%)

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

10/31 (32.26%)

8/31 (25.81%)

Gastrointestinal disorders

Abdominal Pain¹,^†

# participants affected / at risk

6/31 (19.35%)

3/31 (9.68%)

Gastrointestinal disorders

Dyspepsia¹,^†

# participants affected / at risk

4/31 (12.90%)

0/31 (0.00%)

Gastrointestinal disorders

Abdominal Pain Upper¹,^†

# participants affected / at risk

3/31 (9.68%)

2/31 (6.45%)

Gastrointestinal disorders

Dry Mouth¹,^†

# participants affected / at risk

2/31 (6.45%)

3/31 (9.68%)

Gastrointestinal disorders

Oral Pain¹,^†

# participants affected / at risk

3/31 (9.68%)

0/31 (0.00%)

Gastrointestinal disorders

Dysphagia¹,^†

# participants affected / at risk

2/31 (6.45%)

Gastrointestinal disorders

Gastrooesophageal Reflux Disease¹,^†

# participants affected / at risk

2/31 (6.45%)

1/31 (3.23%)

Gastrointestinal disorders

Gingival Bleeding¹,^†

# participants affected / at risk

2/31 (6.45%)

1/31 (3.23%)

Gastrointestinal disorders

Toothache¹,^†

# participants affected / at risk

2/31 (6.45%)

0/31 (0.00%)

General disorders

Fatigue¹,^†

# participants affected / at risk

19/31 (61.29%)

8/31 (25.81%)

General disorders

Asthenia¹,^†

# participants affected / at risk

6/31 (19.35%)

0/31 (0.00%)

General disorders

Oedema Peripheral¹,^†

# participants affected / at risk

3/31 (9.68%)

General disorders

Pyrexia¹,^†

# participants affected / at risk

3/31 (9.68%)

2/31 (6.45%)

General disorders

Chills¹,^†

# participants affected / at risk

2/31 (6.45%)

1/31 (3.23%)

General disorders

Injection Site Pain¹,^†

# participants affected / at risk

1/31 (3.23%)

2/31 (6.45%)

General disorders

Non-Cardiac Chest Pain¹,^†

# participants affected / at risk

2/31 (6.45%)

0/31 (0.00%)

General disorders

Pain¹,^†

# participants affected / at risk

2/31 (6.45%)

1/31 (3.23%)

Infections and infestations

Urinary Tract Infection¹,^†

# participants affected / at risk

4/31 (12.90%)

2/31 (6.45%)

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

1/31 (3.23%)

3/31 (9.68%)

Infections and infestations

Upper Respiratory Tract Infection¹,^†

# participants affected / at risk

3/31 (9.68%)

2/31 (6.45%)

Infections and infestations

Weight Decreased¹,^†

# participants affected / at risk

6/31 (19.35%)

0/31 (0.00%)

Infections and infestations

Weight Increased¹,^†

# participants affected / at risk

0/31 (0.00%)

3/31 (9.68%)

Metabolism and nutrition disorders

Anorexia¹,^†

# participants affected / at risk

12/31 (38.71%)

2/31 (6.45%)

Metabolism and nutrition disorders

Decreased Appetite¹,^†

# participants affected / at risk

2/31 (6.45%)

0/31 (0.00%)

Musculoskeletal and connective tissue disorders

Back Pain¹,^†

# participants affected / at risk

5/31 (16.13%)

8/31 (25.81%)

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

6/31 (19.35%)

7/31 (22.58%)

Musculoskeletal and connective tissue disorders

Pain In Extremity¹,^†

# participants affected / at risk

6/31 (19.35%)

5/31 (16.13%)

Musculoskeletal and connective tissue disorders

Bone Pain¹,^†

# participants affected / at risk

3/31 (9.68%)

5/31 (16.13%)

Musculoskeletal and connective tissue disorders

Musculoskeletal Pain¹,^†

# participants affected / at risk

5/31 (16.13%)

2/31 (6.45%)

Musculoskeletal and connective tissue disorders

Myalgia¹,^†

# participants affected / at risk

4/31 (12.90%)

3/31 (9.68%)

Musculoskeletal and connective tissue disorders

Muscular Weakness¹,^†

# participants affected / at risk

3/31 (9.68%)

0/31 (0.00%)

Musculoskeletal and connective tissue disorders

Musculoskeletal Chest Pain¹,^†

# participants affected / at risk

3/31 (9.68%)

2/31 (6.45%)

Musculoskeletal and connective tissue disorders

Neck Pain¹,^†

# participants affected / at risk

2/31 (6.45%)

Nervous system disorders

Headache¹,^†

# participants affected / at risk

11/31 (35.48%)

7/31 (22.58%)

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

5/31 (16.13%)

3/31 (9.68%)

Nervous system disorders

Dysgeusia¹,^†

# participants affected / at risk

5/31 (16.13%)

0/31 (0.00%)

Nervous system disorders

Paraesthesia¹,^†

# participants affected / at risk

1/31 (3.23%)

3/31 (9.68%)

Nervous system disorders

Hypoaesthesia¹,^†

# participants affected / at risk

0/31 (0.00%)

2/31 (6.45%)

Nervous system disorders

Peripheral Sensory Neuropathy¹,^†

# participants affected / at risk

0/31 (0.00%)

2/31 (6.45%)

Nervous system disorders

Somnolence¹,^†

# participants affected / at risk

2/31 (6.45%)

Psychiatric disorders

Anxiety¹,^†

# participants affected / at risk

1/31 (3.23%)

3/31 (9.68%)

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

1/31 (3.23%)

2/31 (6.45%)

Reproductive system and breast disorders

Breast Pain¹,^†

# participants affected / at risk

1/31 (3.23%)

3/31 (9.68%)

Respiratory, thoracic and mediastinal disorders

Dysphonia¹,^†

# participants affected / at risk

11/31 (35.48%)

0/31 (0.00%)

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

6/31 (19.35%)

4/31 (12.90%)

Respiratory, thoracic and mediastinal disorders

Epistaxis¹,^†

# participants affected / at risk

4/31 (12.90%)

1/31 (3.23%)

Respiratory, thoracic and mediastinal disorders

Oropharyngeal Pain¹,^†

# participants affected / at risk

4/31 (12.90%)

3/31 (9.68%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

3/31 (9.68%)

Respiratory, thoracic and mediastinal disorders

Dry Throat¹,^†

# participants affected / at risk

2/31 (6.45%)

1/31 (3.23%)

Skin and subcutaneous tissue disorders

Dry Skin¹,^†

# participants affected / at risk

4/31 (12.90%)

0/31 (0.00%)

Skin and subcutaneous tissue disorders

Erythema¹,^†

# participants affected / at risk

3/31 (9.68%)

2/31 (6.45%)

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

2/31 (6.45%)

3/31 (9.68%)

Skin and subcutaneous tissue disorders

Alopecia¹,^†

# participants affected / at risk

1/31 (3.23%)

2/31 (6.45%)

Skin and subcutaneous tissue disorders

Hyperkeratosis¹,^†

# participants affected / at risk

2/31 (6.45%)

0/31 (0.00%)

Skin and subcutaneous tissue disorders

Palmar-Plantar Erythrodysaesthesia Syndrome¹,^†

# participants affected / at risk

2/31 (6.45%)

0/31 (0.00%)

Skin and subcutaneous tissue disorders

Pruritus¹,^†

# participants affected / at risk

1/31 (3.23%)

2/31 (6.45%)

Skin and subcutaneous tissue disorders

Skin Hyperpigmentation¹,^†

# participants affected / at risk

2/31 (6.45%)

0/31 (0.00%)

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

16/31 (51.61%)

6/31 (19.35%)

Vascular disorders

Hot Flush¹,^†

# participants affected / at risk

3/31 (9.68%)

11/31 (35.48%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 11.1
2	Term from vocabulary,

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Gerard Lynch
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

CSR-D8480C00007.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Contact Backup

AstraZeneca Cancer Locator Service

877-400-4656

astrazeneca@emergingmed.com

Investigators

Principal Investigator

Bijoyesh Mookerjee

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

CSR-D8480C00007.pdf

Trial Results Summaries