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)
54
Enrollment
36
Locations
1
Arm
19
Duration (Months)
1.5
Patients Per Site
0.1
Patients Per Site Per Month

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

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

ArmIntervention/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

SiteCityStateCountryPostal Code
1Research SitePalo AltoCaliforniaUnited States
2Research SiteSan BernardinoCaliforniaUnited States
3Research SiteSouthingtonConnecticutUnited States
4Research SiteMiamiFloridaUnited States
5Research SiteAtlantaGeorgiaUnited States
6Research SiteMariettaGeorgiaUnited States
7Research SiteChicagoIllinoisUnited States
8Research SiteScarboroughMaineUnited States
9Research SiteAnn ArborMichiganUnited States
10Research SiteMinneapolisMinnesotaUnited States
11Research SiteHackensackNew JerseyUnited States
12Research SiteMorristownNew JerseyUnited States
13Research SiteNew YorkNew YorkUnited States
14Research SiteCharlotteNorth CarolinaUnited States
15Research SitePhiladelphiaPennsylvaniaUnited States
16Research SiteWoonsocketRhode IslandUnited States
17Research SiteSeattleWashingtonUnited States
18Research SiteMorgantownWest VirginiaUnited States
19Research SiteVancouverBritish ColumbiaCanada
20Research SiteHalifaxNova ScotiaCanada
21Research SiteTorontoOntarioCanada
22Research SiteMontrealQuebecCanada
23Research SiteQuebecCanada
24Research SiteBerlinGermany
25Research SiteDresdenGermany
26Research SiteDusseldorfGermany
27Research SiteMunchenGermany
28Research SiteMunsterGermany
29Research SiteBarcelonaSpain
30Research SiteMadridSpain
31Research SiteLeedsWest YorkshireUnited Kingdom
32Research SiteGlasgowUnited Kingdom
33Research SiteLondonUnited Kingdom
34Research SiteManchesterUnited Kingdom
35Research SiteSouthamptonUnited Kingdom
36Research SiteSurreyUnited 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.
Responsible Party:
, ,
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

Study Results

Participant Flow

Recruitment DetailsPatients 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 DetailFollowing 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 TitleAZD4877
Arm/Group DescriptionAZD4877 25 mg (Intravenous (IV), 25mg weekly)
Period Title: Overall Study
STARTED41
COMPLETED0
NOT COMPLETED41

Baseline Characteristics

Arm/Group TitleAZD4877
Arm/Group DescriptionAZD4877 25 mg (Intravenous (IV), 25mg weekly)
Overall Participants41
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
TitleObjective Response Rate (ORR) as Evaluated by Response Evaluation Criteria In Solid Tumors (RECIST)
DescriptionPercentage 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 Frame8 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 TitleAZD4877
Arm/Group DescriptionAZD4877 25 mg (Intravenous (IV), 25mg weekly)
Measure Participants39
Number [Percengate of participants]
2.6
6.3%
2. Secondary Outcome
TitleDisease Control Rate (DCR)
DescriptionPercentage 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 Frame8 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 TitleAZD4877
Arm/Group DescriptionAZD4877 25 mg (Intravenous (IV), 25mg weekly)
Measure Participants39
Number [Percentage of participants]
20.5
50%
3. Secondary Outcome
TitleDuration of Objective Tumor Response (OTR)
DescriptionTime 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 FrameTime 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
TitleProgression Free Survival (PFS)
DescriptionTime 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 FrameTime 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 TitleAZD4877
Arm/Group DescriptionAZD4877 25 mg (Intravenous (IV), 25mg weekly)
Measure Participants39
Median (Full Range) [Weeks]
7.3
5. Secondary Outcome
TitleOverall Survival (OS)
DescriptionTime in weeks from the first administration of study drug to death.
Time FrameTime 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 TitleAZD4877
Arm/Group DescriptionAZD4877 25 mg (Intravenous (IV), 25mg weekly)
Measure Participants39
Median (Full Range) [Weeks]
23.1

Adverse Events

Time Frame
Adverse Event Reporting Description
Arm/Group TitleAZD4877
Arm/Group DescriptionAZD4877 25 mg (Intravenous (IV), 25mg weekly)
All Cause Mortality
AZD4877
Affected / at Risk (%)# Events
Total/ (NaN)
Serious Adverse Events
AZD4877
Affected / at Risk (%)# Events
Total14/41 (34.1%)
Blood and lymphatic system disorders
Leukopenia1/41 (2.4%)
Neutropenia1/41 (2.4%)
Cardiac disorders
Acute Myocardial Infarction1/41 (2.4%)
Cardiac Failure Congestive1/41 (2.4%)
Ventricular Arrhythmia1/41 (2.4%)
Gastrointestinal disorders
Abdominal Pain1/41 (2.4%)
General disorders
Chest Pain1/41 (2.4%)
Death1/41 (2.4%)
Fatigue1/41 (2.4%)
Infections and infestations
Urinary Tract Infection2/41 (4.9%)
Infection1/41 (2.4%)
Injury, poisoning and procedural complications
Narcotic Intoxication1/41 (2.4%)
Metabolism and nutrition disorders
Dehydration2/41 (4.9%)
Psychiatric disorders
Mental Status Changes1/41 (2.4%)
Renal and urinary disorders
Haematuria1/41 (2.4%)
Renal Failure Acute1/41 (2.4%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea1/41 (2.4%)
Pulmonary Embolism1/41 (2.4%)
Other (Not Including Serious) Adverse Events
AZD4877
Affected / at Risk (%)# Events
Total38/41 (92.7%)
Blood and lymphatic system disorders
Neutropenia23/41 (56.1%)
Anaemia11/41 (26.8%)
Leukopenia7/41 (17.1%)
Gastrointestinal disorders
Nausea11/41 (26.8%)
Constipation8/41 (19.5%)
Vomiting8/41 (19.5%)
Abdominal Pain5/41 (12.2%)
Diarrhoea5/41 (12.2%)
Abdominal Discomfort3/41 (7.3%)
Abdominal Distension3/41 (7.3%)
General disorders
Fatigue13/41 (31.7%)
Pyrexia7/41 (17.1%)
Asthenia5/41 (12.2%)
Influenza Like Illness4/41 (9.8%)
Oedema Peripheral4/41 (9.8%)
Infections and infestations
Urinary Tract Infection11/41 (26.8%)
Oral Candidiasis3/41 (7.3%)
Weight Decreased5/41 (12.2%)
Metabolism and nutrition disorders
Anorexia7/41 (17.1%)
Musculoskeletal and connective tissue disorders
Back Pain5/41 (12.2%)
Arthralgia3/41 (7.3%)
Groin Pain3/41 (7.3%)
Neck Pain3/41 (7.3%)
Nervous system disorders
Headache4/41 (9.8%)
Lethargy4/41 (9.8%)
Psychiatric disorders
Insomnia5/41 (12.2%)
Renal and urinary disorders
Haematuria3/41 (7.3%)
Pollakiuria3/41 (7.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea5/41 (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.

Results Point of Contact

Name/TitleGerard Lynch
OrganizationAstraZeneca
Phone
Emailaztrial_results_posting@astrazeneca.com
Responsible Party:
, ,
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