A Phase II Study of AZD4877 (a Novel Anti-mitotic Agent) in Advanced Bladder Cancer

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00661609
• Collaborator: (none)
• Enrollment: 54
• Locations: 36
• Arm: 1
• Duration (Months): 19
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this Phase II study is to determine if AZD4877, an experimental drug that is a novel anti-mitotic agent (Eg5 or Kinesin Spindle Protein inhibitor that interferes with tumor cell division leading to tumor growth), can reduce tumor sizes in patients with bladder cancer

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer; Transitional Cell Bladder Cancer; Urethra Cancer; Ureter Cancer; Renal Pelvis Cancer	Drug: AZD4877	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AZD4877 Single agent AZD4877	Drug: AZD4877; Intravenous (IV)25mg/weekly

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) as Evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) [8 weeks after study drug begins & and every 8 wks thereafter until discontinuation of study drug ( maximum treatment period of 309 days (44 weeks)]

   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).

Secondary Outcome Measures

1. Disease Control Rate (DCR) [8 weeks after study drug begins & every 8 weeks thereafter until discontinuation of the study ( maximum treatment period of 309 days (44 weeks)]

   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).

2. Duration of Objective Tumor Response (OTR) [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)]

   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)

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

   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.

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

   Time in weeks from the first administration of study drug to death.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Confirmed urothelial cancer (cancer of the bladder, renal pelvis, ureter, or urethra).

• Tumor, Node, Metastasis (TNM) Stage IV urothelial cancer that can not be helped by curative surgery and/or curative radiotherapy

• Must have had a maximum of 2 prior chemotherapeutic regimens, one for unremovable and/or metastasized disease, and the other in the adjuvant or neo-adjuvant setting.

• Ambulatory and capable of all selfcare more than 50% of waking hours

Exclusion Criteria:

• Prior treatment with investigational or standard anti-cancer agents, including radiotherapy, within 4 weeks prior to first dose of study medication; 6 weeks if prior systemic mitomycin, nitrosourea, or suramin.

• Inadequate bone marrow reserve

• Inadequate liver function in the presence of liver metastases

• Impaired renal function

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Palo Alto	California	United States
2	Research Site	San Bernardino	California	United States
3	Research Site	Southington	Connecticut	United States
4	Research Site	Miami	Florida	United States
5	Research Site	Atlanta	Georgia	United States
6	Research Site	Marietta	Georgia	United States
7	Research Site	Chicago	Illinois	United States
8	Research Site	Scarborough	Maine	United States
9	Research Site	Ann Arbor	Michigan	United States
10	Research Site	Minneapolis	Minnesota	United States
11	Research Site	Hackensack	New Jersey	United States
12	Research Site	Morristown	New Jersey	United States
13	Research Site	New York	New York	United States
14	Research Site	Charlotte	North Carolina	United States
15	Research Site	Philadelphia	Pennsylvania	United States
16	Research Site	Woonsocket	Rhode Island	United States
17	Research Site	Seattle	Washington	United States
18	Research Site	Morgantown	West Virginia	United States
19	Research Site	Vancouver	British Columbia	Canada
20	Research Site	Halifax	Nova Scotia	Canada
21	Research Site	Toronto	Ontario	Canada
22	Research Site	Montreal	Quebec	Canada
23	Research Site	Quebec		Canada
24	Research Site	Berlin		Germany
25	Research Site	Dresden		Germany
26	Research Site	Dusseldorf		Germany
27	Research Site	Munchen		Germany
28	Research Site	Munster		Germany
29	Research Site	Barcelona		Spain
30	Research Site	Madrid		Spain
31	Research Site	Leeds	West Yorkshire	United Kingdom
32	Research Site	Glasgow		United Kingdom
33	Research Site	London		United Kingdom
34	Research Site	Manchester		United Kingdom
35	Research Site	Southampton		United Kingdom
36	Research Site	Surrey		United Kingdom

Sponsors and Collaborators

• AstraZeneca

Investigators

• Principal Investigator: Gary Hudes, MD, Fox Chase Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00661609
• Other Study ID Numbers: D2782C00010
• First Posted: Apr 18, 2008
• Last Update Posted: Jan 12, 2011
• Last Verified: Dec 1, 2010

• Keywords provided by , ,: Anti-mitotic; Eg5 Inhibitor; Kinesin Spindle Protein Inhibitor; Urothelial Cancer; Bladder Cancer; Renal Pelvis Cancer; Urethra Cancer; Ureter Cancer; Recurrent; Advanced; Stage IV
• Additional relevant MeSH terms: Urinary Bladder Neoplasms; Ureteral Neoplasms; Pelvic Neoplasms; Urethral Neoplasms

Study Results

Participant Flow

Recruitment Details	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 Detail	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.

Arm/Group Title	AZD4877
Arm/Group Description	AZD4877 25 mg (Intravenous (IV), 25mg weekly)
Period Title: Overall Study
STARTED	41
COMPLETED	0
NOT COMPLETED	41

Baseline Characteristics

Arm/Group Title	AZD4877
Arm/Group Description	AZD4877 25 mg (Intravenous (IV), 25mg weekly)
Overall Participants	41
Age, Customized (Number) [Number]
>=18 - <65 Years	17 41.5%
>=65 - <75 Years	19 46.3%
>=75 Years	5 12.2%
Sex: Female, Male (Count of Participants)
Female	11 26.8%
Male	30 73.2%
Race/Ethnicity, Customized (participants) [Number]
White	40 97.6%
Black and African	1 2.4%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR) as Evaluated by Response Evaluation Criteria In Solid Tumors (RECIST)
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)

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	AZD4877
Arm/Group Description	AZD4877 25 mg (Intravenous (IV), 25mg weekly)
Measure Participants	39
Number [Percengate of participants]	2.6 6.3%

2. Secondary Outcome

Title	Disease Control Rate (DCR)
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)

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	AZD4877
Arm/Group Description	AZD4877 25 mg (Intravenous (IV), 25mg weekly)
Measure Participants	39
Number [Percentage of participants]	20.5 50%

3. Secondary Outcome

Title	Duration of Objective Tumor Response (OTR)
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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Progression Free Survival (PFS)
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)

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	AZD4877
Arm/Group Description	AZD4877 25 mg (Intravenous (IV), 25mg weekly)
Measure Participants	39
Median (Full Range) [Weeks]	7.3

5. Secondary Outcome

Title	Overall Survival (OS)
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)

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	AZD4877
Arm/Group Description	AZD4877 25 mg (Intravenous (IV), 25mg weekly)
Measure Participants	39
Median (Full Range) [Weeks]	23.1

Adverse Events

Arm/Group Title	AZD4877
Arm/Group Description	AZD4877 25 mg (Intravenous (IV), 25mg weekly)
All Cause Mortality
	AZD4877
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	AZD4877
	Affected / at Risk (%)	# Events
Total	14/41 (34.1%)
Blood and lymphatic system disorders
Leukopenia	1/41 (2.4%)
Neutropenia	1/41 (2.4%)
Cardiac disorders
Acute Myocardial Infarction	1/41 (2.4%)
Cardiac Failure Congestive	1/41 (2.4%)
Ventricular Arrhythmia	1/41 (2.4%)
Gastrointestinal disorders
Abdominal Pain	1/41 (2.4%)
General disorders
Chest Pain	1/41 (2.4%)
Death	1/41 (2.4%)
Fatigue	1/41 (2.4%)
Infections and infestations
Urinary Tract Infection	2/41 (4.9%)
Infection	1/41 (2.4%)
Injury, poisoning and procedural complications
Narcotic Intoxication	1/41 (2.4%)
Metabolism and nutrition disorders
Dehydration	2/41 (4.9%)
Psychiatric disorders
Mental Status Changes	1/41 (2.4%)
Renal and urinary disorders
Haematuria	1/41 (2.4%)
Renal Failure Acute	1/41 (2.4%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/41 (2.4%)
Pulmonary Embolism	1/41 (2.4%)
Other (Not Including Serious) Adverse Events
	AZD4877
	Affected / at Risk (%)	# Events
Total	38/41 (92.7%)
Blood and lymphatic system disorders
Neutropenia	23/41 (56.1%)
Anaemia	11/41 (26.8%)
Leukopenia	7/41 (17.1%)
Gastrointestinal disorders
Nausea	11/41 (26.8%)
Constipation	8/41 (19.5%)
Vomiting	8/41 (19.5%)
Abdominal Pain	5/41 (12.2%)
Diarrhoea	5/41 (12.2%)
Abdominal Discomfort	3/41 (7.3%)
Abdominal Distension	3/41 (7.3%)
General disorders
Fatigue	13/41 (31.7%)
Pyrexia	7/41 (17.1%)
Asthenia	5/41 (12.2%)
Influenza Like Illness	4/41 (9.8%)
Oedema Peripheral	4/41 (9.8%)
Infections and infestations
Urinary Tract Infection	11/41 (26.8%)
Oral Candidiasis	3/41 (7.3%)
Weight Decreased	5/41 (12.2%)
Metabolism and nutrition disorders
Anorexia	7/41 (17.1%)
Musculoskeletal and connective tissue disorders
Back Pain	5/41 (12.2%)
Arthralgia	3/41 (7.3%)
Groin Pain	3/41 (7.3%)
Neck Pain	3/41 (7.3%)
Nervous system disorders
Headache	4/41 (9.8%)
Lethargy	4/41 (9.8%)
Psychiatric disorders
Insomnia	5/41 (12.2%)
Renal and urinary disorders
Haematuria	3/41 (7.3%)
Pollakiuria	3/41 (7.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	5/41 (12.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.