Gemcitabine Hydrochloride and Cisplatin With or Without Bevacizumab in Treating Patients With Advanced Urinary Tract Cancer
Condition: Advanced Urothelial Carcinoma; Metastatic Bladder Urothelial Carcinoma; Metastatic Prostate Carcinoma; Metastatic Renal Pelvis Urothelial Carcinoma; Metastatic Ureter Urothelial Carcinoma; Metastatic Urethral Urothelial Carcinoma; Metastatic Urothelial Carcinoma; Stage IV Bladder Urothelial Carcinoma AJCC v7; Stage IV Prostate Cancer AJCC v7; Stage IV Renal Pelvis Cancer AJCC v7; Stage IV Ureter Cancer AJCC v7; Stage IV Urethral Cancer AJCC v7; Unresectable Urothelial Carcinoma
MeSH terms: Carcinoma; Carcinoma, Transitional Cell; Urethral Neoplasms; Ureteral Neoplasms; Pelvic Neoplasms
Intervention: Bevacizumab; Cisplatin; Gemcitabine Hydrochloride; Laboratory Biomarker Analysis; Placebo Administration
Intervention description: Given IV; Given IV; Given IV; Correlative studies; Given IV
Intervention MeSH terms: Bevacizumab; Antineoplastic Agents, Immunological; Cisplatin; Gemcitabine; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 506.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial studies gemcitabine hydrochloride, cisplatin, and bevacizumab
      to see how well they work compared with gemcitabine hydrochloride and cisplatin in treating
      patients with urinary tract cancer that has spread to other places in the body. 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, by stopping them from dividing, or by
      stopping them from spreading. Immunotherapy with bevacizumab, may induce changes in body's
      immune system and may interfere with the ability of tumor cells to grow and spread. It is not
      yet known whether gemcitabine hydrochloride and cisplatin are more effective when given with
      or without bevacizumab in treating patients with urinary tract cancer.
    

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

               -  For patients that have had surgical resection prior to study enrollment, residual
                  or unresected disease (measurable and/or unmeasurable) must be evident on
                  post-surgical scans

          -  Prior treatment for transitional cell carcinoma (TCC)

               -  Patients may not have received combination systemic chemotherapy for metastatic
                  disease

               -  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 the
                  interval from end of therapy to diagnosis of metastatic disease is at least 1
                  year

               -  >= 4 weeks since any prior radiation (including palliative) or major surgery and
                  fully recovered

               -  >= 7 days since any minor surgery such as port placement

               -  >= 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 > 35
                  mIU/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 0-1 (or Karnofsky
             performance status [KPS] >= 80)

          -  Absolute neutrophil count (ANC) >= 1,500/uL

          -  Platelet count >= 100,000/uL

          -  Calculated or measured creatinine clearance >= 50 mL/minute

          -  Bilirubin =< 1.25 times upper limits of normal; for patients with Gilbert's disease,
             =< 2.5 x upper limit of normal (ULN) is allowed

          -  Aspartate aminotransferase (AST) =< 2.0 x upper limits of normal

          -  Urine protein to creatinine ratio < 1.0 or urine protein =< 1+ or 24-hour urine
             protein =< 1 gram