Gemzar, Cisp, Sunitinib Urothelial Ca
Condition: Urothelial Cancer
Intervention: Gemcitabine, Cisplatin, Sunitinib
Intervention description: Patients will receive gemcitabine 800 mg/m2 IV (Days 1 and 8), cisplatin 60 mg/m2 IV (Day 1), and sunitinib 37.5 mg PO daily (Days 1-14) of each 21-day cycle.
2. One cycle of treatment is defined as 21 days (3 weeks). Restaging studies will be performed after every 3 cycles of therapy.
3. Successive cycles will be initiated every 3 weeks, and will be continued through 6 cycles unless a patient shows evidence of disease progression or intolerable toxicity.
Intervention MeSH terms: Gemcitabine; Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of this nonrandomized Phase II study is to evaluate the objective
      response rate (ORR, CR+PR) in patients with advanced/metastatic UC treated with the
      combination of gemcitabine, cisplatin, and sunitinib.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Has histological documentation of diagnosis of transitional cell carcinoma (TCC) of
             the bladder, urethra, ureter, or renal pelvis (histology may be mixed, but still
             requires a component of TCC; measurable disease only)

          2. Has unresectable or metastatic disease

          3. Has a Karnofsky Performance Status greater than or equal 60 percent

          4. Is 18 years of age or older

          5. Has laboratory values as defined by the protocol

          6. Has resolution of all acute toxic effects of prior chemotherapy or radiotherapy or
             surgical procedures to NCI CTCAE (v3.0) Grade less than or equal to 1

          7. Has normal cardiac function as evidenced by a LVEF greater than or equal to 50
             percent, as determined by multiple gated acquisition (MUGA) scan or an echocardiogram
             (ECHO). The same method must be used throughout the study to evaluate LVEF.

          8. Has a negative serum pregnancy test within 7 calendar days prior to registration
             (female patients of childbearing potential [not surgically sterilized and between
             menarche and 1 year postmenopausal])

          9. Is not currently breastfeeding

         10. If fertile, patient (male or female) has agreed to use an acceptable method of birth
             control to avoid pregnancy for the duration of the study and for a period of 3 months
             thereafter.

         11. Has signed a Patient Informed Consent Form, Has signed a Patient Authorization Form

        Exclusion Criteria:

          1. Has had prior treatment with systemic chemotherapy (prior intravesical therapy is
             permitted)

          2. Has had major surgery or radiation therapy within 4 weeks of starting the study
             treatment

          3. Has had NCI CTCAE (Version 3.0) Grade 3-4 hemorrhage within 4 weeks of starting the
             study treatment

          4. Has a history of or known spinal cord compression, or carcinomatous meningitis, or
             evidence of symptomatic brain or leptomeningeal disease on screening CT or MRI scan.
             However treated, stable and asymptomatic brain metastases are allowed.

          5. Has had any of the following within the 6 months prior to study drug administration:
             myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
             graft, symptomatic congestive heart failure, cerebrovascular accident or transient
             ischemic attack, or pulmonary embolism

          6. Has ongoing cardiac dysrhythmias of NCI CTCAE (Version 3.0) Grade 2

          7. Has prolonged QTc interval on baseline EKG

          8. Has uncontrolled hypertension (grater than 150/100 mm Hg despite optimal medical
             therapy)

          9. Has pre-existing thyroid abnormality with thyroid function that cannot be maintained
             in the normal range with medication

         10. Has known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
             (AIDS)-related illness or other active infection

         11. Is receiving concomitant use of any other investigational drugs or has received such
             drug within 28 days prior to registration

         12. Is receiving concurrent treatment on another clinical trial, including supportive care

         13. Has ongoing treatment with therapeutic doses of warfarin (low dose warfarin up to 2 mg
             PO daily for thromboembolic prophylaxis allowed). Patients on warfarin (greater than
             2mg) for thrombosis must be switched to low molecular weight heparin (ie, Lovenox),
             prior to registration for protocol therapy.

         14. Is currently taking drugs having proarrhythmic potential (terfenadine, quinidine,
             procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone,
             indapamide and flecainide) within 7 days prior to Day 1 of Cycle 1 (dosing) (and
             throughout study)

         15. Is currently on CYP3A4 inhibitors (see Section 5) within 7 days prior to Day 1 of
             Cycle 1 (dosing), with the exception of amiodarone, which should be discontinued
             within 6 months prior to Day 1 of Cycle 1 (dosing)

         16. Is currently on CYP3A4 inducers (see Section 5) within 14 days prior to Day 1 of Cycle
             1 (dosing)

         17. Has been taking herbal or alternative medications within the past 7 days or refuses to
             discontinue the use of herbal or alternative therapies within 7 days prior to Day 1 of
             Cycle 1 (dosing)

         18. Has a serious uncontrolled intercurrent medical or psychiatric illness, including
             serious infection

         19. Has a history of other malignancy within the last 5 years (except cured basal cell
             carcinoma of skin and carcinoma in situ of uterine cervix), which could affect the
             diagnosis or assessment of any of the study drugs.

         20. Is a pregnant or nursing woman. Patients must be surgically sterile or be
             postmenopausal, or must agree to use effective contraception during the period of
             therapy. The definition of effective contraception will be based on the judgment of
             the Study Investigator or Treating Physician. Male patients must be surgically sterile
             or agree to use effective contraception.

        Is unable to comply with requirements of study