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A Phase II Safety and Efficacy Study With the VEGF Receptor Tyrosine Kinase Inhibitor GW786034 in Patients With Metastatic Urothelial Cancer

Phase 2
18 Years
Not Enrolling
Anterior Urethral Cancer, Posterior Urethral Cancer, Recurrent Bladder Cancer, Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter, Recurrent Urethral Cancer, Stage IV Bladder Cancer, Transitional Cell Carcinoma of the Bladder, Urethral Cancer Associated With Invasive Bladder Cancer

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Trial Information

A Phase II Safety and Efficacy Study With the VEGF Receptor Tyrosine Kinase Inhibitor GW786034 in Patients With Metastatic Urothelial Cancer


I. Assess the anti tumor activity and toxicity profile of pazopanib hydrochloride in
patients with metastatic urothelial cancer.


I. Evaluate the pharmacokinetics of pazopanib hydrochloride in these patients. II. Evaluate
pre- and post-treatment changes in circulating endothelial cells, monocytes and platelets,
and angiogenesis-related factors in these patients.

OUTLINE: This is a multicenter study. Patients receive oral pazopanib hydrochloride once
daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or
unacceptable toxicity.

Patients undergo blood collection periodically for correlative studies and pharmacological
studies. Samples are analyzed for vascular endothelial growth factor (VEGF) and soluble VEGF
receptor II concentration via ELISA. Circulating endothelial cells are also measured.

After completion of study treatment, patients are followed for 1 year.

Inclusion Criteria:

- Histologically or cytologically confirmed transitional cell cancer of the urothelium
or bladder

- Metastatic disease

- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 2.0 cm by
conventional techniques OR ≥ 1.0 cm by spiral CT scan

- No known brain metastases

- ECOG performance status 0−2

- Life expectancy ≥ 12 weeks

- Platelet count ≥ 100,000/mm^3

- WBC ≥ 3,000/mm^3

- Absolute neutrophil count ≥ 1,500/mm^3

- Bilirubin normal

- AST and ALT ≤ 2.5 times upper limit of normal (ULN)

- Creatinine normal OR creatinine clearance ≥ 60 mL/min

- PT/INR/PTT ≤ 1.2 times ULN

- No proteinuria > 1+ on two consecutive dipsticks measured ≥ 1 week apart

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to pazopanib hydrochloride or other agents used in the study

- No condition that impairs the ability to swallow and retain pazopanib hydrochloride
tablets, including any of the following:

- Gastrointestinal tract disease resulting in an inability to take oral medication

- Requirement for IV alimentation

- Prior surgical procedures affecting absorption

- Active peptic ulcer disease

- No uncontrolled illness that would limit compliance with study therapy including,
but not limited to, any of the following:

- Ongoing or active infection

- Psychiatric illness or social situations

- No QTc prolongation (defined as a QTc interval ≥ 480 msecs) or other significant ECG
abnormalities (e.g., frequent ventricular ectopy, evidence of ongoing myocardial

- No other conditions, including any of the following:

- Serious or non-healing wound, ulcer, or bone fracture

- Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
within the past 28 days

- Cerebrovascular accident within the past 6 months

- Myocardial infarction, cardiac arrhythmia, or admission for unstable angina
within the past 12 weeks

- Venous thrombosis within the past 12 weeks

- New York Heart Association (NYHA) class III or IV heart failure

- Asymptomatic NYHA class II heart failure on treatment allowed

- No other active second malignancy other than non-melanoma skin cancer

- Patients are not considered to have an active malignancy if they have completed
anti-cancer therapy and are considered by their physician to be ≤ 30% risk of

- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
and recovered

- At least 4 weeks since prior radiotherapy

- Prior palliative radiotherapy to metastatic lesions allowed provided there is ≥ 1
measurable and/or evaluable lesion(s) that has not been irradiated

- At least 4 weeks since prior surgery

- One prior chemotherapy regimen for metastatic urothelial or bladder cancer

- More than 12 weeks since prior cardiac angioplasty or stenting

- Prior adjuvant or neoadjuvant therapy allowed

- No prior experimental treatment for metastatic disease

- No other prior or concurrent investigational agents

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent CYP2C9 substrates

- No other concurrent anticancer agents or therapies

- No concurrent medications that are associated with a risk of QTc prolongation and/or
Torsades de Pointes

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Best Tumor Response (Complete [CR] or Partial Response [PR] by Response Evaluation Criteria in Solid Tumors [RECIST])

Outcome Description:

Tumor response is defined as the total number of eligible patients whose disease has a complete or partial response to GW786034 according to the RECIST criteria. Per RECIST v1.0 criteria: A Complete Response (CR) requires the disappearance of all target lesions. A Partial Response (PR) requires >=30% decrease in the sum of the longest diameter of target lesions from baseline measurement. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for response.

Outcome Time Frame:

Participants will be evaluated every 8 weeks during treatment and up to 1 year after completion of treatment.

Safety Issue:


Principal Investigator

Ulka Vaishampayan

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

August 2008

Completion Date:

December 2010

Related Keywords:

  • Anterior Urethral Cancer
  • Posterior Urethral Cancer
  • Recurrent Bladder Cancer
  • Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter
  • Recurrent Urethral Cancer
  • Stage IV Bladder Cancer
  • Transitional Cell Carcinoma of the Bladder
  • Urethral Cancer Associated With Invasive Bladder Cancer
  • Urinary Bladder Neoplasms
  • Carcinoma
  • Carcinoma, Transitional Cell
  • Urethral Neoplasms
  • Kidney Neoplasms
  • Ureteral Neoplasms



University of Wisconsin Hospital and ClinicsMadison, Wisconsin  53792-0001
Mayo Clinic Cancer Research ConsortiumRochester, Minnesota  55905