Phase II Trial of Gemcitabine, Carboplatin, and Bevacizumab in Chemotherapy Naive Patients With Advanced/Metastatic Urothelial Carcinoma
Condition: Myeloproliferative Disorder; Urothelial Carcinoma; Cancer
MeSH terms: Carcinoma; Carcinoma, Transitional Cell; Myeloproliferative Disorders
Intervention: Bevacizumab; Carboplatin; Gemcitabine
Intervention MeSH terms: Bevacizumab; Carboplatin; Gemcitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 51.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Myeloproliferative Disorder; urinary bladder; Cancer; ureter; renal pelvis; chemotherapy

Summary:

      Gemcitabine and carboplatin are two standard chemotherapy drugs used to treat tumors of the
      urothelial tract. These drugs do not shrink tumors in all patients and when they do, it is
      generally for a limited amount of time. This has led scientists to look for different ways to
      treat cancer.

      New drugs have been developed to treat cancer that work differently than standard
      chemotherapy drugs. One new class of drugs are called 'angiogenesis-inhibitors'. These drugs
      attempt to decrease the blood supply to tumors. By doing so, this may limit the tumor's
      source of oxygen and nutrients and prevent the tumor from growing. Bevacizumab is an
      anti-angiogenic drug.

      In some other cancers such as colon cancer and lung cancer, combining bevacizumab with
      standard chemotherapy shrinks tumors in a greater proportion of patients and makes patients
      live longer than using standard chemotherapy alone. This has never been tested in urothelial
      cancer and we do not know if bevacizumab will have the same effects in this disease. The
      purpose of this study is to find out what effects, good and/or bad, the combination of
      gemcitabine, carboplatin, and bevacizumab has on you and your cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologic documentation: diagnosis of transitional cell carcinoma of the
             bladder,urethra, ureter, or renal pelvis.

          -  Unresectable or metastatic disease

          -  Ineligible for cisplatin (or incurable with cisplatin)

          -  ≥ 4 weeks since prior RT

          -  Karnofsky Performance Status ≥ 60%

          -  Age ≥ 18 years of age

          -  Required Initial Laboratory Values: Absolute neutrophil count ≥ 1.2 x 109/L; Platelets
             ≥ 100 x 109/L; Bilirubin ≤ 1.5 times the upper limit of normal (x ULN) for the
             institution; Aspartate transaminase (AST) and alanine transaminase(ALT) ≤ 3.0 x
             ULN;Serum creatinine < 2.0 or calculated creatinine clearance (CrCl) ≥ 30 mL/min

        Exclusion Criteria:

          -  Prior treatment with systemic chemotherapy (prior intravesical therapy is permitted)

          -  Current, recent (within 4 weeks of the first infusion of this study), or planned
             participation in an experimental drug study other than a Genentech-sponsored
             bevacizumab cancer study

          -  Blood pressure of >150/100 mmHg

          -  Unstable angina

          -  New York Heart Association (NYHA) Grade II or greater congestive heart failure

          -  History of myocardial infarction within 6 months

          -  History of stroke within 6 months

          -  Clinically significant peripheral vascular disease

          -  Evidence of bleeding diathesis or coagulopathy

          -  Presence of central nervous system or brain metastases

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to Day 0

          -  Anticipation of need for major surgical procedure during the course of the study

          -  Minor surgical procedures such as fine needle aspirations or core biopsies within 7
             days prior to Day 0

          -  Pregnant (positive pregnancy test) or lactating

          -  Albuminuria as demonstrated by a urinary albumin of greater or = to 1.0 g/24 hr at
             screening

          -  History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess
             within 6 months prior to Day 0

          -  Serious, non-healing wound, ulcer, or bone fracture

          -  Inability to comply with study and/or follow-up procedures

          -  History of persistent gross hematuria