Phase 2 study with the multi-targeted tyrosine-kinase inhibitor Pazopanib (GW786034) for patients with relapsed or refractory urothelial cancer - Pazopanib for pre-treated urothelial cancer

Conditions: rothelial cancer
MedDRA version: 9.1Level: LLTClassification code 10064467

Registration Number: EUCTR2009-017093-20-IT

Lead Sponsor: ISTITUTO NAZIONALE PER LA CURA TUMORI

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

Age > 18 years Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. Life expectancy of at least 12 weeks. Histologically confirmed diagnosis of transitional cell tumors of the bladder or the urothelium. Metastatic disease. Measurable disease criteria, defined as ≥ 1 unidimensionally measurable lesion ≥ 2 cm by conventional techniques or ≥ 1 cm by spiral CT scan. Failure of at least one cisplatin-based conventional chemotherapy regimen for metastatic disease (neoadjuvant/adjuvant therapy excluded). Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening: Hemoglobin ≥ 9.0 gr/dL Absolute neutrophil count (ANC) ≥ 1.000/μL Platelet count ≥ 75.000/μL Total bilirubin ≤ 1.5 times the ULN ALT and AST ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement of their cancer) Alkaline phosphatase ≤ 4 x ULN Serum creatinine ≤1.5 mg/dL PT-INR/PTT < 1.5 x ULN [Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.] Written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

History of cardiac disease: congestive heart failure > NYHA class 2; active CAD; cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension. History of HIV infection or active chronic hepatitis B or C. Active clinically serious infections (> grade 2 NCI-CTC version 3.0). Symptomatic metastatic brain or meningeal tumors Patients with seizure disorder requiring medication (such as steroids or anti-epileptics). Patients with evidence or history of bleeding diathesis. Patients undergoing renal dialysis. Previous or concurrent 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. Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and three months after the completion of trial. Substance abuse, medical, psychological or social conditions that may interfere with the patient s participation in the study or evaluation of the study results. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study. Patients unable to swallow oral medications. Excluded therapies and medications, previous and concomitant 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. (Palliative radiotherapy will be allowed). Use of biologic response modifiers, such as G-CSF, within 3 week of study entry. [G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator, however they may not be substituted for a required dose reduction.] [Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study]. Prior exposure to pazopanib.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the activity of the drug in patients with relapsed/refractory transitional cell tumors receiving the following treatment program: daily oral doses of Pazopanib monotherapy.;Secondary Objective: To evaluate the safety and tolerability of Pazopanib monotherapy in a population of chemotherapy pretreated patients.;Primary end point(s): Assessment of response-rate by RECIST 1.1 criteria. RR (%) = CR + PR.

Secondary Outcome Measures