Gemcitabine Hydrochloride and Cisplatin With or Without Bevacizumab in Treating Patients With Advanced Urinary Tract Cancer


Bladder | Distal Urethral Cancer | Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter | Proximal Urethral Cancer | Recurrent Bladder Cancer | Recurrent Prostate Cancer | Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter | Recurrent Urethral Cancer | Stage IV Bladder Cancer | Stage IV Prostate Cancer | Transitional Cell Carcinoma of the Bladder | Urethral Cancer Associated With Invasive Bladder Cancer

Trial Phase

Phase III

Trial Purpose and Description

Trial Purpose

This randomized phase III trial is studying gemcitabine hydrochloride, cisplatin, and bevacizumab to see how well they work compared with gemcitabine hydrochloride, cisplatin, and placebo in treating patients with advanced urinary tract cancer. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether gemcitabine hydrochloride and cisplatin are more effective when given together with or without bevacizumab in treating patients with urinary tract cancer.

Participation Guidelines

18 Years and older

Eligibility Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically documented metastatic or
    unresectable transitional cell (urothelial) carcinoma of the urinary tract (renal
    pelvis, ureter, bladder, prostate, or urethra), with metastatic or locally advanced
    disease (T4b, N2, N3, or M1) patients must not be candidates for potentially
    curative surgery or radiotherapy
  • Patients may not have received prior combination systemic chemotherapy for metastatic
  • For the purposes of this study, radiosensitizing single-agent chemotherapy is
    not considered prior systemic therapy
  • Prior neoadjuvant or adjuvant systemic chemotherapy is permissible provided it
    was completed >= 1 year prior to the diagnosis of metastatic disease
  • At least 4 weeks since prior radiation (including palliative) or major surgery and
    fully recovered
  • At least 7 days since any minor surgery such as port placement
  • At least 4 weeks since any intravesical therapy
  • No prior treatment with bevacizumab or other angiogenesis inhibitors
  • No known history of brain metastases brain imaging (magnetic resonance imaging
    [MRI]/computed tomography [CT]) is not required
  • No current congestive heart failure New York Heart Association (NYHA) class II, III
    or IV
  • Patients with history of hypertension must be well controlled (< 150/90) on a regimen
    of anti-hypertensive therapy
  • Patients on full-dose anticoagulants must be on a stable dose of warfarin and have an
    in-range international normalized ratio (INR) (usually between 2 and 3) or be on a
    stable dose of low molecular weight (LMW) heparin patients receiving anti-platelet
    agents are also eligible in addition, patients who are on daily prophylactic aspirin
    or anticoagulation for atrial fibrillation are eligible
  • No significant history of bleeding events or gastrointestinal (GI) perforation
  • Patients with a history of a significant bleeding episode (e.g. hemoptysis,
    upper or lower GI bleeding, grade 3 or 4 gross hematuria unable to be controlled
    by trans-urethral resection of the bladder tumor) within 6 months of
    registration are not eligible
  • Patients with a history of GI perforation within 12 months of registration are
    not eligible
  • Patients with a history of peritoneal carcinomatosis are not eligible
  • No arterial thrombotic events within 6 months of registration, including transient
    ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial thrombus,
    unstable angina or angina requiring surgical or medical intervention in the past 6
    months, or myocardial infarction (MI) patients with clinically significant
    peripheral artery disease (i.e., claudication on less than one block) are ineligible
  • Patients who have experienced a deep venous thrombosis or pulmonary embolus within
    the past 6 months must be on stable therapeutic anticoagulation to be enrolled to
    this study
  • No serious or non-healing wound, ulcer, or bone fracture
  • No sensory or motor peripheral neuropathy >= grade 2
  • Patients with known hypersensitivity to Chinese hamster ovary cell products or other
    recombinant human antibodies are not eligible
  • Patients that are pregnant or nursing are not eligible women of child bearing
    potential must have a negative serum or urine pregnancy test (minimum sensitivity 25
    IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours prior
    to registration
  • For women of child-bearing potential with an elevated beta-HCG that is believed
    to be related to cancer and not pregnancy, a negative trans-vaginal ultrasound
    and gynecological examination are required
  • Women of child-bearing potential include any female who has experienced menarche
    and who has not undergone surgical sterilization (hysterectomy, bilateral tubal
    ligation or bilateral oophorectomy) or is not postmenopausal [defined as
    amenorrhea >= 12 consecutive months or women on hormone replacement therapy
    [HRT] with documented serum follicle stimulating hormone [FSH] level >
    35mIU/mL) even women who are using oral, implanted or injectable contraceptive
    hormones or mechanical products such as an intrauterine device or barrier
    methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing
    abstinence or where partner is sterile (e.g., vasectomy), should be considered
    to be of child bearing potential
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 OR Karnofsky PS
    >= 80
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Calculated or measured creatinine clearance >= 50 mL/minute
  • Bilirubin =< 1.25 times upper limit of normal (ULN) (for patients with Gilbert's
    Disease, =< 2.5 X ULN is allowed)
  • Aspartate aminotransferase (AST) =< 2.0 times ULN
  • Urine protein to creatinine ratio < 1.0 OR urine protein =< 1+ OR 24-hour urine
    protein =< 1 gram
National Cancer Institute (NCI)
Last Updated:
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