A Randomized Phase III Trial of Leukine® vs Neupogen® in Patients Receiving Cisplatin and Gemcitabine for Regionally Advanced or Metastatic Urothelial Cancer
Objectives: To compare the efficacy of Leukine and Neupogen in the treatment of patients
receiving cisplatin and gemcitabine for regionally advanced or metastatic urothelial cancer
in regard to reduction of grade 3 and 4 neutropenia. Secondary objectives include a
comparison of: hematologic and non-hematologic toxicities, anti-tumor effects, dose
intensity, and quality of life in each treatment arm.
Methodology: The study will be a multi-institutional, randomized, phase III study in
patients with regionally advanced or metastatic urothelial cancer. All patients will
receive chemotherapy with cisplatin plus gemcitabine for six 21-day cycles. Patients will
receive hematopoietic growth factor support with either Leukine (Arm A), or Neupogen (Arm
B). Rates of anti-tumor responses and the incidence of toxicities in each treatment arm
will provide a comparison of efficacy and safety for the hematopoietic support regimens.
Patient Population: Patients to be enrolled (n=100) in this study will have received a
diagnosis of regionally advanced or metastatic urothelial cancer of the bladder, ureter, or
renal pelvis and will have not undergone previous systemic chemotherapy. Approximately 50
patients will be enrolled into each treatment arm.
Main Criteria for Inclusion: Inclusion criteria for this study specify that patients have
evaluable, biopsy-proven, surgically unresectable, regionally advanced, or metastatic
urothelial cancer of the bladder, ureter, or renal pelvis. Additionally, patients must have
an Eastern Cooperative Oncology Group performance status of 0-2 and adequate bone marrow,
renal, and hepatic function. Patients who have undergone previous systemic chemotherapy will
be excluded from this study.
Test Product, Dose, Mode of Administration: All patients will receive chemotherapeutic
treatment with cisplatin (70 mg/kg) intravenously on Day 1 and gemcitabine (1000 mg/m2)
intravenously on Days 1, 8, and 15 of each 21-day cycle. Patients will be randomized to
receive either Leukine (250 µg/m2) or Neupogen (5 µg/kg) subcutaneously on Days 2-6, 9-13,
and 16-20 of each cycle.
Duration of Treatment: Patients will receive a maximum of six 21-day cycles of treatment.
The overall trial, including follow-up, is expected to be 3 years in duration.
Criteria for Evaluation: Efficacy will be assessed by, incidence of grade 3 and 4
toxicities, evaluation of complete and partial response, time to progression, overall and
disease specific survival, planned vs administered doses, and quality of life. Safety will
be assessed by, vital signs, physical examinations, clinical laboratory evaluations, and the
reporting of adverse events.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Efficacy of Leukine & Neupogen to prevent grade 3 & 4 neutropenia in patients receiving cisplatin & gemcitabine: assessed before cycles 3 & 5, then at end of treatment.
John Rinehart, MD
University of Kentucky
United States: Food and Drug Administration
|New York Medical College||Valhalla, New York 10595|
|Montefiore Medical Center||Bronx, New York 10467-2490|
|University of Louisville||Louisville, Kentucky 40202|
|University of Nebraska||Omaha, Nebraska 68198|