An Open-Label, Multicenter, Randomized Phase Ib/II Study of Eribulin Mesylate Administered in Combination With Gemcitabine Plus Cisplatin Versus Gemcitabine Plus Cisplatin Alone as First-Line Therapy for Locally Advanced or Metastatic Bladder Cancer
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 >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
Interventional
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety parameters
Safety parameters: adverse events (AEs); vital signs; ECOG PS; clinical laboratory evaluations; physical examinations; and 12 lead electrocardiograms (ECGs).
[Time Frame: AEs and conmeds - until study termination; lab tests Day 1 and every 21 days until study termination; ECGs - Day 1 and 21 days after therapy ended
Yes
United States: Food and Drug Administration
E7389-702
NCT01126749
April 2010
September 2014
Name | Location |
---|---|
Mayo Clinic | Rochester, Minnesota 55905 |
University of Michigan Comprehensive Cancer Center | Ann Arbor, Michigan 48109-0752 |
Virginia Oncology Associates | Newport News, Virginia 23606 |
Comprehensive Cancer Centers of Nevada | Las Vegas, Nevada 89109 |
Florida Cancer Specialists | Fort Myers, Florida 33901 |
UAB Comprehensive Cancer Center | Birmingham, Alabama 35294 |
Texas Oncology P.A. | Dallas, Texas 75230-2503 |
Tower Cancer Research Foundation | Beverly Hills, California 90211 |
Arizona Clinical Research Center, Inc. | Tucson, Arizona 85712 |
East Orange VA Medical Center | East Orange, New Jersey 07018 |
Chattanooga Oncology and Hematology Associates, PC | Chattanooga, Tennessee 37404 |
Florida Cancer Specialists-Broadway | Ft. Myers, Florida 33916 |
Tennessee Cancer Specialist | Knoxville, Tennessee 37909 |
TX Oncology- Deke Slaton Ca Ctr | Webster, Texas 77598 |
Texas Oncology Memorial City | Houston, Texas 77024 |