A Phase II study of AZD4877 (a novel anti-mitotic agent) in advanced bladder cancer

Study identifier:D2782C00010

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase II, Single Arm, Single Agent, Multicentre, Adaptive 2-Stage Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of AZD4877 Administered Weekly in Patients with Recurrent Advanced Urothelial Cancer

Medical condition

Bladder Cancer

Phase

Phase 2

Healthy volunteers

Study drug

AZD4877

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years +

Date

Study Start Date: 01 May 2008

Primary Completion Date: 01 May 2009

Study Completion Date: 01 Dec 2009

Study design

Allocation: N/A
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Dec 2010 by AstraZeneca Pharmaceuticals

Collaborators

Inclusion and exclusion criteria

Location

Research Site

VANCOUVER, BC, Canada

Location

Research Site

HALIFAX, NS, Canada

Location

Research Site

TORONTO, ON, Canada

Location

Research Site

MONTREAL, QC, Canada

Location

Research Site

QUEBEC, QC, Canada

Location

Research Site

BERLIN, Germany

Location

Research Site

DRESDEN, Germany

Location

Research Site

DUSSELDORF, Germany

Arms	Assigned Interventions
Experimental: AZD4877 Single agent AZD4877	Drug: AZD4877 Intravenous (IV)25mg/weekly

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients were recruited at 23 study sites in 5 countries: United States (7 centers), United Kingdom (6 centers), Germany (5 centers), Canada (3 centers), and Spain (2 centers) between 29 May 2008 and 11 January 2010. 54 participants were enrolled into the study of which 41 participants received at least one dose of study medication.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Following enrolment there was a screening period of up to 28 days, after which if all inclusion/exclusion criteria were met, patients were dosed with AZD4877.

Reporting Groups

	Description
AZD4877	AZD4877 25 mg (Intravenous (IV), 25mg weekly)

Participant Flow: Overall Study

	AZD4877
STARTED	41^[1]
COMPLETED	0^[2]
NOT COMPLETED	41
Adverse Event	4
Death	20
Withdrawal by Subject	2
PI Decision	1
Survival follow up stage discontinued	11
Disease progression	3

[1]	All dosed patients
[2]	Treatment is not for a fixed period and continues until a discontinuation criterion is met.

Baseline Characteristics

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

Reporting Groups

	Description
AZD4877	AZD4877 25 mg (Intravenous (IV), 25mg weekly)

Baseline Measures

	AZD4877
Number of Participants [units: Participants]	41
Age, Customized [units: Participants]
>=18 - <65 Years	17
>=65 - <75 Years	19
>=75 Years	5
Gender, Male/Female [units: Participants]
Female	11
Male	30
RaceEthnicityOther [units: participants]
White	40
Black and African	1

Outcome Measures

1. Primary Outcome Measure: Objective Response rate (ORR) as evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) [ Time Frame: 8 weeks after study drug begins & and every 8 wks thereafter until discontinuation of study drug ( maximum treatment period of 309 days (44 weeks) ]

Measure Type	Primary
Measure Name	Objective Response rate (ORR) as evaluated by Response Evaluation Criteria In Solid Tumors (RECIST)
Measure Description	Percentage of participants with complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST), version 1.0 (Therasse et al. Natl Cancer Inst 92 (2000) pp205-216).
Time Frame	8 weeks after study drug begins & and every 8 wks thereafter until discontinuation of study drug ( maximum treatment period of 309 days (44 weeks)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Of the 41 participants who received at least one dose of study medication, only 39 were evaluable for response by RECIST (excludes 2 patients who had baseline scans performed more than 28 days before dosing).

Reporting Groups

	Description
AZD4877	AZD4877 25 mg (Intravenous (IV), 25mg weekly)

Measured Values

	AZD4877
Number of Participants Analyzed [units:participants]	39
Objective Response rate (ORR) as evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) [units: Percengate of participants]	2.6

No statistical analysis provided for Objective Response rate (ORR) as evaluated by Response Evaluation Criteria In Solid Tumors (RECIST)

2. Secondary Outcome Measure: Disease Control Rate (DCR) [ Time Frame: 8 weeks after study drug begins & every 8 weeks thereafter until discontinuation of the study ( maximum treatment period of 309 days (44 weeks) ]

Measure Type	Secondary
Measure Name	Disease Control Rate (DCR)
Measure Description	Percentage of participants with Complete Response (CR), Partial Response (PR), or stable disease (SD) lasting at least 8 weeks from the first administration of study drug. RECIST guidelines:(Response evaluation criteria in solid tumors, version 1.0).
Time Frame	8 weeks after study drug begins & every 8 weeks thereafter until discontinuation of the study ( maximum treatment period of 309 days (44 weeks)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Of the 41 participants who received at least one dose of study medication, only 39 were evaluable for response by RECIST (excludes 2 patients who had baseline scans performed more than 28 days before dosing).

Reporting Groups

	Description
AZD4877	AZD4877 25 mg (Intravenous (IV), 25mg weekly)

Measured Values

	AZD4877
Number of Participants Analyzed [units:participants]	39
Disease Control Rate (DCR) [units: Percentage of participants]	20.5

No statistical analysis provided for Disease Control Rate (DCR)

3. Secondary Outcome Measure: Duration of Objective Tumor Response (OTR) [ Time Frame: Time from first documentation of Complete or Partial Response, whichever occurs earlier, to discontinuation of the study drug (maximum treatment period of 309 days (44 weeks) ]

Measure Type	Secondary
Measure Name	Duration of Objective Tumor Response (OTR)
Measure Description	Time in weeks from the date of Complete Response (CR) or Partial Response (PR), whichever occurs earlier, to the date of discontinuation of study. RECIST guidelines:(Response evaluation criteria in solid tumors, version 1.0)
Time Frame	Time from first documentation of Complete or Partial Response, whichever occurs earlier, to discontinuation of the study drug (maximum treatment period of 309 days (44 weeks)
Safety Issue?	No

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

4. Secondary Outcome Measure: Progression Free Survival (PFS) [ Time Frame: Time from the first administration of study drug to disease progression or death (maximum treatment period of 309 days (44 weeks) ]

Measure Type	Secondary
Measure Name	Progression Free Survival (PFS)
Measure Description	Time in weeks from date of first study drug administration to the date of progressive disease according to the RECIST guidelines (Response evaluation in solid tumors, version 1.0), or death due to any cause.
Time Frame	Time from the first administration of study drug to disease progression or death (maximum treatment period of 309 days (44 weeks)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Of the 41 participants who received at least one dose of study medication, only 39 were evaluable for response by RECIST (excludes 2 patients who had baseline scans performed more than 28 days before dosing).

Reporting Groups

	Description
AZD4877	AZD4877 25 mg (Intravenous (IV), 25mg weekly)

Measured Values

	AZD4877
Number of Participants Analyzed [units:participants]	39
Progression Free Survival (PFS) [units: Weeks] Median (Full Range)	7.3 (0 to 44)

No statistical analysis provided for Progression Free Survival (PFS)

5. Secondary Outcome Measure: Overall Survival (OS) [ Time Frame: Time from the first administration of study drug to disease progression or death (maximum treatment period of 309 days (44 weeks) ]

Measure Type	Secondary
Measure Name	Overall Survival (OS)
Measure Description	Time in weeks from the first administration of study drug to death.
Time Frame	Time from the first administration of study drug to disease progression or death (maximum treatment period of 309 days (44 weeks)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Of the 41 participants who received at least one dose of study medication, only 39 were evaluable for response by RECIST (excludes 2 patients who had baseline scans performed more than 28 days before dosing).

Reporting Groups

	Description
AZD4877	AZD4877 25 mg (Intravenous (IV), 25mg weekly)

Measured Values

	AZD4877
Number of Participants Analyzed [units:participants]	39
Overall Survival (OS) [units: Weeks] Median (Full Range)	23.1 (1.3 to 48.1)

No statistical analysis provided for Overall Survival (OS)

Serious Adverse Events

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

Reporting Groups

	Description
AZD4877	AZD4877 25 mg (Intravenous (IV), 25mg weekly)

Serious Adverse Events

AZD4877

Total, serious adverse events

# participants affected / at risk

14/41 (34.15%)

Blood and lymphatic system disorders

Leukopenia¹,^†

# participants affected / at risk

1/41 (2.44%)

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

1/41 (2.44%)

Cardiac disorders

Acute Myocardial Infarction¹,^†

# participants affected / at risk

1/41 (2.44%)

Cardiac disorders

Cardiac Failure Congestive¹,^†

# participants affected / at risk

1/41 (2.44%)

Cardiac disorders

Ventricular Arrhythmia¹,^†

# participants affected / at risk

1/41 (2.44%)

Gastrointestinal disorders

Abdominal Pain¹,^†

# participants affected / at risk

1/41 (2.44%)

General disorders

Chest Pain¹,^†

# participants affected / at risk

1/41 (2.44%)

General disorders

Death¹,^†

# participants affected / at risk

1/41 (2.44%)

General disorders

Fatigue¹,^†

# participants affected / at risk

1/41 (2.44%)

Infections and infestations

Urinary Tract Infection¹,^†

# participants affected / at risk

2/41 (4.88%)

Infections and infestations

Infection¹,^†

# participants affected / at risk

1/41 (2.44%)

Injury, poisoning and procedural complications

Narcotic Intoxication¹,^†

# participants affected / at risk

1/41 (2.44%)

Metabolism and nutrition disorders

Dehydration¹,^†

# participants affected / at risk

2/41 (4.88%)

Psychiatric disorders

Mental Status Changes¹,^†

# participants affected / at risk

1/41 (2.44%)

Renal and urinary disorders

Haematuria¹,^†

# participants affected / at risk

1/41 (2.44%)

Renal and urinary disorders

Renal Failure Acute¹,^†

# participants affected / at risk

1/41 (2.44%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

1/41 (2.44%)

Respiratory, thoracic and mediastinal disorders

Pulmonary Embolism¹,^†

# participants affected / at risk

1/41 (2.44%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 12.0
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
AZD4877	AZD4877 25 mg (Intravenous (IV), 25mg weekly)

Other Adverse Events

AZD4877

Total, other (not including serious) adverse events

# participants affected / at risk

38/41 (92.68%)

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

23/41 (56.10%)

Blood and lymphatic system disorders

Anaemia²,^†

# participants affected / at risk

11/41 (26.83%)

Blood and lymphatic system disorders

Leukopenia²,^†

# participants affected / at risk

7/41 (17.07%)

Gastrointestinal disorders

Nausea²,^†

# participants affected / at risk

11/41 (26.83%)

Gastrointestinal disorders

Constipation²,^†

# participants affected / at risk

8/41 (19.51%)

Gastrointestinal disorders

Vomiting^†

# participants affected / at risk

8/41 (19.51%)

Gastrointestinal disorders

Abdominal Pain²,^†

# participants affected / at risk

5/41 (12.20%)

Gastrointestinal disorders

Diarrhoea²,^†

# participants affected / at risk

5/41 (12.20%)

Gastrointestinal disorders

Abdominal Discomfort²,^†

# participants affected / at risk

3/41 (7.32%)

Gastrointestinal disorders

Abdominal Distension²,^†

# participants affected / at risk

3/41 (7.32%)

General disorders and administration site conditions

Fatigue²,^†

# participants affected / at risk

13/41 (31.71%)

General disorders and administration site conditions

Pyrexia²,^†

# participants affected / at risk

7/41 (17.07%)

General disorders and administration site conditions

Asthenia²,^†

# participants affected / at risk

5/41 (12.20%)

General disorders and administration site conditions

Influenza Like Illness²,^†

# participants affected / at risk

4/41 (9.76%)

General disorders and administration site conditions

Oedema Peripheral²,^†

# participants affected / at risk

4/41 (9.76%)

Infections and infestations

Urinary Tract Infection²,^†

# participants affected / at risk

11/41 (26.83%)

Infections and infestations

Oral Candidiasis²,^†

# participants affected / at risk

3/41 (7.32%)

Infections and infestations

Weight Decreased²,^†

# participants affected / at risk

5/41 (12.20%)

Metabolism and nutrition disorders

Anorexia²,^†

# participants affected / at risk

7/41 (17.07%)

Musculoskeletal and connective tissue disorders

Back Pain²,^†

# participants affected / at risk

5/41 (12.20%)

Musculoskeletal and connective tissue disorders

Arthralgia²,^†

# participants affected / at risk

3/41 (7.32%)

Musculoskeletal and connective tissue disorders

Groin Pain²,^†

# participants affected / at risk

3/41 (7.32%)

Musculoskeletal and connective tissue disorders

Neck Pain²,^†

# participants affected / at risk

3/41 (7.32%)

Nervous system disorders

Headache²,^†

# participants affected / at risk

4/41 (9.76%)

Nervous system disorders

Lethargy²,^†

# participants affected / at risk

4/41 (9.76%)

Psychiatric disorders

Insomnia²,^†

# participants affected / at risk

5/41 (12.20%)

Renal and urinary disorders

Haematuria²,^†

# participants affected / at risk

3/41 (7.32%)

Renal and urinary disorders

Pollakiuria²,^†

# participants affected / at risk

3/41 (7.32%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea²,^†

# participants affected / at risk

5/41 (12.20%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 12.0
2	Term from vocabulary, MedDRA (12.0)
3	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: An Investigator agrees to provide a copy of the publication to AZ for review at least 60 days in advance of submission for publication. Investigators in multicenter (MC) studies agree to postpone MC publications until the earlier of the date of the first AZ-authorized MC publication or a period up to 18 months from study completion at all sites. AZ has the right to request delays: up to 60 days for confidential information, and an additional 90 days to protect intellectual property.

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

Cancer Study Locator (US and Canada only)
Download
https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=310&filename=CSR-D2782C00010.pdf
Download
CSR-D2782C00010.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Locator Service

877-400-4656

astrazeneca@emergingmed.com

Contact Backup

AstraZeneca Clinical Study Information

800-236-9933

information.center@astrazeneca.com

Investigators

Principal Investigator

Gary Hudes

Fox Chase Cancer Center

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Cancer Study Locator (US and Canada only)

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=310&filename=CSR-D2782C00010.pdf

CSR-D2782C00010.pdf

Trial Results Summaries