Phase II Pazopanib in Combination With Weekly Paclitaxel in Refractory Urothelial Cancer
Condition: Bladder Cancer; Bladder (Urothelial, Transitional Cell) Cancer; Bladder (Urothelial, Transitional Cell) Cancer Superficial (Non-Invasive); Bladder (Urothelial, Transitional Cell) Cancer Resectable (Pre-Cystectomy); Bladder (Urothelial, Transitional Cell) Cancer Metastatic or Unresectable
MeSH terms: Urinary Bladder Neoplasms
Intervention: Pazopanib (GW786034); Paclitaxel
Intervention description: Cycle of 28 days. Pazopanib: 800mg/day; Cycle of 28 days Paclitaxel: 80mg/m2 days 1,8 and 15
Intervention MeSH terms: Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      We will combine an oral investigational vascular endothelial growth factor (VEGF inhibitor)
      called pazopanib which is being studied in kidney cancer will be combined with standard
      chemotherapy called taxol in patients with relapsed recurrent urothelial cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically confirmed transitional cell carcinoma (TCC) of the urothelium (bladder,
             renal pelvis, ureter, or urethra). Mixed histology is allowed as long as the
             predominant histology is TCC

          2. First recurrence after treatment with a maximum of two chemotherapeutic regimens.

          3. Subjects must provide written informed consent prior to performance of study-specific
             procedures or assessments, and must be willing to comply with treatment and follow up.

             Procedures conducted as part of the subject's routine clinical management (eg, blood
             count, imaging study) and obtained prior to signing of informed consent may be
             utilized for screening or baseline purposes provided these procedures are conducted as
             specified in the protocol.

          4. Age ≥ 18 years

          5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

          6. Measurable disease criteria by RECIST criteria

          7. Adequate organ system function as defined below

               1. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L

               2. Hemoglobin ≥ 9 g/dL

               3. Platelets ≥ 100 X 10^9/L

               4. Prothrombin time (PT) or international normalized ratio (INR) ≤ 1.2 x upper limit
                  of normal (ULN)

               5. Total bilirubin ≤ 1.5 x ULN

               6. aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT)≤ 2.5 x ULN

               7. Serum creatinine ≤ 1.8 mg/dL

               8. Urine Protein to Creatinine Ratio (UPC) < 1

          8. A female is eligible to enter and participate in this study if she is of
             non-childbearing potential (ie, physiologically incapable of becoming pregnant). This
             includes any female who has had:

               -  A hysterectomy

               -  A bilateral oophorectomy (ovariectomy)

               -  A bilateral tubal ligation

               -  Menopause

        Childbearing potential females must have a negative serum pregnancy test within 2 weeks
        prior to the first dose of study treatment, preferably as close to the first dose as
        possible, and agree to use adequate contraception. Adequate acceptable contraceptive
        methods, when used consistently and in accordance with both the product label and the
        instructions of the physician, are as follow:

          -  An intrauterine device with a documented failure rate of less than 1% per year.

          -  Vasectomized partner who is sterile prior to the female subject's entry and is the
             sole sexual partner for that female.

          -  Complete abstinence from sexual intercourse for 14 days before exposure to
             investigational product, through the dosing period, and for at least 21 days after the
             last dose of investigational product.

          -  Double-barrier contraception (condom with spermicidal jelly, foam suppository, or
             film; diaphragm with spermicide; or male condom and diaphragm with spermicide).

        Exclusion Criteria:

          1. History of other malignancies within 5 years prior to Day 1 except for tumors with a
             negligible risk for metastasis or death, such as adequately controlled basal cell
             carcinoma, squamous-cell carcinoma of the skin, carcinoma in situ of the cervix,
             early-stage bladder cancer, or low-grade endometrial cancer Malignancies that have
             undergone a putative surgical cure (ie, localized prostate cancer post-prostatectomy)
             within 5 years prior to Day 1 may be discussed with the Medical Monitor

          2. History or clinical evidence of central nervous system (CNS) metastases or
             leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS
             metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure
             medication for 6 months prior to first dose of study drug.

          3. Clinically significant gastrointestinal abnormalities that may increase the risk for
             GI bleeding

          4. Clinically significant gastrointestinal abnormalities that may affect absorption of
             the investigational product

          5. Presence of uncontrolled infection.

          6. Prolongation of corrected QT interval (QTc) > 480 milliseconds. On antiarrhythmics or
             medications known to prolong QT interval

          7. History of any one or more of the following cardiovascular conditions within the past
             6 months:

               -  Cardiac angioplasty or stenting

               -  Myocardial infarction

               -  Unstable angina

               -  Coronary artery by-pass graft surgery

               -  Symptomatic peripheral vascular disease

               -  Class III or IV congestive heart failure, as defined by the New York Heart
                  Association (NYHA)

          8. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥ 140 mmHg
             or diastolic blood pressure (DBP) of ≥ 90mm Hg].

          9. History of cerebrovascular accident, hemoptysis, cerebral hemorrhage, clinically
             significant GI bleed, pulmonary embolism or untreated deep venous thrombosis (DVT)
             within the past 6 months

         10. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or
             presence of any non-healing wound, fracture

         11. Evidence of active bleeding or bleeding diathesis.

         12. Any serious and/or unstable pre-existing medical, psychiatric, or other condition that
             could interfere with subject's safety, provision of informed consent, or compliance to
             procedures.

         13. Patients on strong CYP3A4 inhibitors

         14. Uncorrected abnormal electrolytes: K, Mg and Ca

         15. Prior treatment with taxane chemotherapy

         16. Treatment with any of the following anti-cancer therapies:

               -  radiation therapy, surgery or tumor embolization within 14 days prior to the
                  first dose of pazopanib OR

               -  chemotherapy, immunotherapy, biologic therapy, investigational therapy or
                  hormonal therapy within 14 days or five half-lives of a drug (whichever is
                  longer) prior to the first dose of pazopanib