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A Randomized Phase III Trial of Leukine® vs Neupogen® in Patients Receiving Cisplatin and Gemcitabine for Regionally Advanced or Metastatic Urothelial Cancer

Phase 3
18 Years
Not Enrolling
Bladder Cancer

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Trial Information

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.

Inclusion Criteria:

- Biopsy-proven, regionally advanced (T4b, N2, N3), or metastatic (M1) urothelial
cancer of the bladder, ureter, or renal pelvis

- A minimum of one target lesion according to the RECIST criteria (Appendix D). Note:
Bone metastases, leptomeningeal disease, ascites, pleural or pericardial effusions,
lymphangitic spread or cystic lesions are not acceptable as target lesions.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (Appendix

- Age >/=18 years or the age of majority in the state of the participating institution.

- Women of childbearing potential must have a negative pregnancy test and must be
willing to consent to using effective contraception while on treatment and for a
reasonable period thereafter. Post menopausal women must have been amenorrheic for
at least 12 months to be considered of non-childbearing potential.

- An expected survival of at least four months.

- Adequate organ and marrow function as defined as follows:

- leukocytes >/=3,000/µl,

- absolute neutrophil count >/=1,500/µl,

- hemoglobin >/=8.0g/dl,

- platelets >/=100,000/µl,

- total bilirubin and serum creatinine must be < 1.5 mg/dl

- liver transaminases (SGOT and/or SGPT) may be up to 2.5 x institutional ULN if
alkaline phosphatase is
- alkaline phosphatase may be up to 4 x ULN if transaminases are
- Patients who have undergone previous radiation therapy or surgery may be enrolled
into the study but such treatment must have been completed 4 or more weeks prior to
entry to the study and the patient must have recovered. Further, patients who have
undergone radiotherapy may not have received radiation to > 25% of the bone marrow.
Previous intravesicular immunotherapy and chemotherapy are allowed.

- Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

- Undergone previous systemic chemotherapy.

- Major surgery <4 weeks prior to study treatment start, or lack of complete recovery
from major surgery.

- Participation in any investigational drug study within 4 weeks preceding treatment

- History of uncontrolled seizures, central nervous system disorders or psychiatric
disability judged by the Investigator to be significant enough to preclude informed
consent or interfering with compliance for oral drug intake.

- Previous history of cancer unless treatment was curative and completed >/=5 years
prior to entry onto study, or unless diagnosed as one of the following: in situ
carcinoma (any location), basal cell carcinoma, or non-metastatic squamous cell
carcinoma of the skin.

- Uncontrolled intercurrent illness including, but not limited to: ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris,
uncontrolled or untreated cardiac arrhythmia, or psychiatric illness/social
situations that would limit compliance with study requirements.

- Pregnant women are excluded from this study because of the teratogenic potential of
cisplatin and gemcitabine. Lactating women are also excluded. (Should a woman
become pregnant or suspect she is pregnant while participating in this study, she
should inform her treating physician immediately.)

- Peripheral neuropathy >/= grade 2.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Principal Investigator

John Rinehart, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Kentucky


United States: Food and Drug Administration

Study ID:




Start Date:

November 2005

Completion Date:

March 2006

Related Keywords:

  • Bladder Cancer
  • urothelial
  • bladder
  • gemcitabine
  • cisplatin
  • leukine
  • neupogen
  • filgrastim
  • sargramostim
  • metastatic
  • Regionally Advanced
  • Advanced
  • Urinary Bladder Neoplasms



New York Medical CollegeValhalla, New York  10595
Montefiore Medical CenterBronx, New York  10467-2490
University of LouisvilleLouisville, Kentucky  40202
University of NebraskaOmaha, Nebraska  68198