Bladder Cancer, Renal Pelvis Cancer, Transitional Cell Bladder Cancer, Ureter Cancer, Urethra Cancer
Conditions
Keywords
Anti-mitotic, Eg5 Inhibitor, Kinesin Spindle Protein Inhibitor, Urothelial Cancer, Bladder Cancer, Renal Pelvis Cancer, Urethra Cancer, Ureter Cancer, Recurrent, Advanced, Stage IV
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
Interventions
DRUGAZD4877
Intravenous (IV)25mg/weekly
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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) |
| 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. |
| 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. |
Countries
Canada, Germany, Spain, United Kingdom, United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| AZD4877 AZD4877 25 mg (Intravenous (IV), 25mg weekly) | 41 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Death | 20 |
| Overall Study | Disease progression | 3 |
| Overall Study | PI Decision | 1 |
| Overall Study | Survival follow up stage discontinued | 11 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | AZD4877 |
|---|---|
| Age, Customized >=18 - <65 Years | 17 Participants |
| Age, Customized >=65 - <75 Years | 19 Participants |
| Age, Customized >=75 Years | 5 Participants |
| Race/Ethnicity, Customized Black and African | 1 participants |
| Race/Ethnicity, Customized White | 40 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 38 / 41 |
| serious Total, serious adverse events | 14 / 41 |
Outcome results
Primary
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).
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)
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| AZD4877 | Objective Response Rate (ORR) as Evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) | 2.6 Percengate of participants |
Secondary
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).
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)
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| AZD4877 | Disease Control Rate (DCR) | 20.5 Percentage of participants |
Secondary
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 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)
Secondary
Overall Survival (OS)
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)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| AZD4877 | Overall Survival (OS) | 23.1 Weeks |
Secondary
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 frame: Time from the first administration of study drug to disease progression or death (maximum treatment period of 309 days (44 weeks)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| AZD4877 | Progression Free Survival (PFS) | 7.3 Weeks |