Clinical trial NCT01126749
Conditions: Bladder Cancer
Keywords: Locally Advanced or Metastatic Bladder Cancer, including other transitional cell cancers of the urothelium (prostate, urethra, ureter, and renal pelvis)
Sponsor: Eisai Inc.
Start date: 2010-04-16; Completion date: 2016-07-20
Enrollment: 92 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine whether Patients with Locally Advanced or Metastatic Bladder Cancer who receive Eribulin Mesylate Administered in Combination with Gemcitabine Plus Cisplatin Versus Gemcitabine Plus Cisplatin Alone as First-Line Therapy is safety and tolerable when administered to patients with locally advanced or metastatic bladder cancer and to gain preliminary data on whether patients may benefit from this combination.

Detailed description:
This open-label, multicenter, randomized study will consist of 2 phases:

* Phase Ib: a safety run-in period with 3 ascending doses of eribulin;
* Phase II: a randomized 2-arm design. Phase Ib Patients will be recruited into cohorts, with a minimum of 3 and a maximum of 6 patients per cohort. All patients will receive the same dose of gemcitabine (1000 mg/m2 on Days 1 and 8 of a 21-day cycle) and cisplatin (70 mg/m2 on Day 1) in combination with eribulin (administered on Days 1 and 8 of the cycle). All patients in a cohort will receive the same dose level of eribulin.

The dose level of eribulin will be escalated for additional cohorts unless greater than 2 dose limiting toxicities (DLTs) are reported at the lower dose level(s) prior to enrollment of the next dose level. If one DLT occurs at any dose level, the cohort will be expanded to include up to a maximum of 6 patients.

A Dose Escalation Committee will determine when no further dose escalation is appropriate and whether the MTD will be defined as a preceding dose or an intermediate dose.

Phase II Patients will be randomized in a 1:1 ratio to receive either eribulin in combination with gemcitabine plus cisplatin (Arm 1) or gemcitabine plus cisplatin alone (Arm 2). The eribulin dose will be 1.0 mg/m2 administered on Days 1 and 8 of each 21-day treatment cycle, the recommended Phase II dose for eribulin when administered in combination gemcitabine plus cisplatin, as determined in the Phase Ib portion of the study.

Allocation of patients will be stratified based on metastatic disease status (patients with visceral metastases versus patients with non-visceral metastases). This stratified randomization will be centrally allocated across all centers via an Interactive Voice Activated Response System (IVRS).

For both the Phase Ib and Phase II portions, 1 cycle of therapy will last 21 days, with a maximum number of 6 gemcitabine plus cisplatin cycles. Radiologic examinations including a computed tomography (CT) scan of the chest, abdomen, and pelvis as appropriate (and CT or magnetic resonance imaging \[MRI\] scan as appropriate), will be performed during Screening and after every 6 weeks while on therapy. In the case of dose delays, scans should be performed according to the original Cycle 1 Day 1 schedule (ie, scans should not be delayed). Radiographic assessments should be repeated at withdrawal if the last assessment was obtained greater than 3 weeks from withdrawal of therapy. Patients will be followed until death following completion of therapy. Scans will be required every 2 months until documentation of PD or the start of a next line of therapy, whichever occurs first. In patients experiencing PD, follow-up will be for survival only and radiographic scans are not required.

Arms: arm 1: None arm 2: None
Interventions: intervention 1: Gemcitabine intervention 2: E7389 intervention 3: Cisplatin
Intervention descriptions: intervention 1: Gemcitabine intervention 2: E7389 intervention 3: Cisplatin

Protocol documents: