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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Bladder Cancer, Transitional Cell Bladder Cancer, Urethra Cancer, Ureter Cancer, Renal Pelvis Cancer

Intervention / Treatment
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* Drug: AZD4877


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD4877<br>Single agent AZD4877 | Drug: AZD4877<br>* Intravenous (IV)25mg/weekly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) as Evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) | 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). | 8 weeks after study drug begins & and every 8 wks thereafter until discontinuation of study drug ( maximum treatment period of 309 days (44 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (DCR) | 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). | 8 weeks after study drug begins & every 8 weeks thereafter until discontinuation of the study ( maximum treatment period of 309 days (44 weeks) | 
| Duration of Objective Tumor Response (OTR) | 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 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) | 
| Progression Free Survival (PFS) | 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 from the first administration of study drug to disease progression or death (maximum treatment period of 309 days (44 weeks) | 
| Overall Survival (OS) | Time in weeks from the first administration of study drug to death. | Time from the first administration of study drug to disease progression or death (maximum treatment period of 309 days (44 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anti-mitotic, Eg5 Inhibitor, Kinesin Spindle Protein Inhibitor, Urothelial Cancer, Bladder Cancer, Renal Pelvis Cancer, Urethra Cancer, Ureter Cancer, Recurrent, Advanced, Stage IV