Phase II Pazopanib in Combination With Weekly Paclitaxel in Refractory Urothelial Cancer

Not Recruiting

Trial ID: NCT01108055


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.

Official Title

A Phase II Study of Pazopanib in Combination With Weekly Paclitaxel in Refractory Urothelial Cancer

Stanford Investigator(s)

Sandy Srinivas
Sandy Srinivas

Professor of Medicine (Oncology) and, by courtesy, of Urology


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

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


drug: Pazopanib (GW786034)

drug: Paclitaxel

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305

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