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Phase 2 Study With the Multi-Targeted Tyrosine-Kinase Inhibitor Pazopanib (GW786034) for Patients With Relapsed or Refractory Urothelial Cancer

Phase 2
18 Years
Open (Enrolling)
Bladder Cancer, Transitional Cell Cancer of the Renal Pelvis and Ureter, Urethral Cancer

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Trial Information

Phase 2 Study With the Multi-Targeted Tyrosine-Kinase Inhibitor Pazopanib (GW786034) for Patients With Relapsed or Refractory Urothelial Cancer



- To evaluate the activity of daily oral doses of pazopanib hydrochloride monotherapy in
patients with relapsed/refractory metastatic urothelial carcinoma or transitional cell


- To evaluate the safety and tolerability of pazopanib hydrochloride monotherapy in a
population of chemotherapy pretreated patients.

- To assess progression-free survival of these patients.


- To evaluate the ability of whole-body 18FDG-PET to image metastases and monitor tumor
response and to determine the rate of concordance with CT imaging and RECIST response

- To evaluate the relationship existing between tumor response measured by 18FDG-PET and
progression-free survival.

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 whole-body 18FDG-PET at baseline and periodically.

After completion of study treatment, patients are followed for 2 years.

Inclusion Criteria


- Histologically confirmed diagnosis of transitional cell tumors of the bladder or the

- Metastatic disease

- Relapsed or refractory disease

- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 2 cm by
conventional techniques or ≥ 1 cm by spiral CT scan

- Must have failed ≥ 1 cisplatin-based conventional chemotherapy regimen for metastatic
disease (neoadjuvant/adjuvant therapy excluded)

- No history or clinical evidence of CNS metastases or leptomeningeal carcinomatosis,
except for individuals who were previously treated for CNS metastases, are
asymptomatic, and have had no requirement for steroids or anti-seizure medication for
the past 6 months


- ECOG performance status 0-1

- Life expectancy ≥ 12 weeks

- Hemoglobin ≥ 9.0 g/dL

- Absolute neutrophil count ≥ 1,000/μL

- Platelet count ≥ 75,000/μL

- Total bilirubin ≤ 1.5 x upper limit of normal (ULN)

- ALT and AST ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement)

- Alkaline phosphatase ≤ 4 x ULN

- Serum creatinine ≤ 1.5 mg/dL

- PT-INR/PTT < 1.5 x ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception during and for 3 months
after completion of study therapy

- Able to swallow oral medication

- None of the following cardiovascular conditions within the past 6 months:

- Cardiac angioplasty or stenting

- Myocardial infarction

- Unstable angina

- Symptomatic peripheral vascular disease

- NYHA class III or IV congestive heart failure

- Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin
are permitted)

- Uncontrolled hypertension

- No history of HIV infection or active chronic hepatitis B or C

- No active clinically serious infections > grade 2 NCI-CTC version 4.0

- No seizure disorder requiring medication (e.g., steroids or anti-epileptics)

- No history of any of the following conditions within the past 6 months:

- Cerebrovascular accident

- Pulmonary embolism

- Untreated deep venous thrombosis

- No evidence or history of bleeding diathesis

- No known endobronchial lesions or involvement of large pulmonary vessels by tumor

- No hemoptysis within the past 6 weeks

- No gastrointestinal abnormalities that may increase the risk of GI bleeding or affect
the absorption of investigational study drug

- No other cancer that is distinct in primary site or histology from the cancer being
evaluated in this study, except cervical carcinoma in situ, treated basal cell
carcinoma, or any cancer curatively treated > 5 years prior to study entry

- No substance abuse, medical, psychological, or social conditions that may interfere
with the study participation or evaluation of the study results

- No concurrent unstable condition that could jeopardize patient safety and their
compliance in the study

- No non-healing wound, fracture, or ulcer within the past 28 days

- No major trauma within the past 28 days

- No known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to pazopanib hydrochloride


- See Disease Characteristics

- Recovered from all prior therapy

- At least 14 days since prior radiotherapy, except palliative radiotherapy

- At least 14 days since tumor embolization

- At least 14 days or 5 half-lives (whichever is longer) of a drug since prior
chemotherapy, immunotherapy, biologic therapy, investigational therapy, or hormonal

- At least 3 weeks since prior biologic response modifiers (e.g., G-CSF)

- G-CSF and other hematopoietic growth factors may be used in the management of
acute toxicity (e.g., febrile neutropenia) when clinically indicated or at the
discretion of the investigator, however they may not be used to avoid a required
dose reduction

- Chronic erythropoietin allowed provided no dose adjustment is undertaken within
2 months prior to the study or during the study

- No prior pazopanib hydrochloride

- No coronary artery by-pass graft surgery within the past 6 months

- No major surgery within the past 28 days

- Concurrent coumadin or heparin for therapeutic anticoagulation allowed provided that
no prior evidence of underlying abnormality in PT-INR/PTT parameters exist

- Not concurrently undergoing renal dialysis

Type of Study:


Study Design:

Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate (complete and partial response) according to RECIST 1.1 criteria

Safety Issue:


Principal Investigator

Roberto Salvioni, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano



Study ID:




Start Date:

December 2009

Completion Date:

Related Keywords:

  • Bladder Cancer
  • Transitional Cell Cancer of the Renal Pelvis and Ureter
  • Urethral Cancer
  • recurrent bladder cancer
  • stage IV bladder cancer
  • recurrent urethral cancer
  • anterior urethral cancer
  • posterior urethral cancer
  • urethral cancer associated with invasive bladder cancer
  • metastatic transitional cell cancer of the renal pelvis and ureter
  • recurrent transitional cell cancer of the renal pelvis and ureter
  • Urinary Bladder Neoplasms
  • Urethral Neoplasms
  • Carcinoma, Transitional Cell
  • Kidney Neoplasms
  • Ureteral Neoplasms