Relapsed or progressive Transitional Cell Carcinoma (TCC) of the urothelium MedDRA version: 14.0 Level: LLT Classification code 10044426 Term: Transitional cell carcinoma urethra System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.0 Level: LLT Classification code 10044420 Term: Transiti
Conditions
Interventions
Trade Name: Votrient
Product Name: Pazopanib Hydrochloride (Votrient)
Product Code: GW786034B
Pharmaceutical Form: Tablet
INN or Propose
Sponsors
NHS Greater Glasgow Health Board
University of Glasgow
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Histologically or cytologically confirmed TCC (bladder, renal pelvis, ureter, urethra), which is locally advanced or metastatic (T4b and/or N1-3 and/or M1). Patients with mixed or differentiation pattern pathology will be permitted entry providing that TCC is a component pathology. 2.Progressive disease during or after one prior platinum-based chemotherapy regimen for advanced disease or as peri-operative therapy for muscle-invasive / node positive disease (if completed 30ml/min (calculated by Cockcroft Gault equation) or Creatinine =1.5 x ULN. •Absolute neutrophil count (ANC) =1500/mm3 without growth factor support •Platelets = 100,000/mm3 •Urine protein to creatinine ratio (UPC) =65 years) yes F.1.3.1 Number of subjects for this age range 98
Exclusion criteria
Exclusion criteria: 1.Congestive heart failure, myocardial infarction, coronary artery bypass graft or thrombotic cerebrovascular event in the previous six months, or ongoing severe or unstable arrhythmia requiring medication. Patients with rate controlled atrial fibrillation are permitted to enter the study. 2.History of clinically significant bleeding in the 6 months prior to study initiation (including haemoptysis, cerebrovascular bleed or haematemesis; patients with haematuria are permitted entry as long as there is no indication for intervention). 3.Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any unhealed wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery). 4.Cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been therapeutically anti-coagulated for at least 6 weeks are eligible. 5.History of another malignancy in the last 5 years (other than treated squamous/basal cell skin cancer, treated early stage cervical cancer or treated / biochemically stable, organ confined prostate cancer). 6.Ongoing major gastrointestinal disease including unstable inflammatory bowel disease or bleeding peptic ulcer disease. 7.Known endobronchial lesions which have a high risk of pulmonary haemorrhage . 8.Previously identified brain, or central nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously-treated CNS metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants in prior 28 days. 9.Pregnant or breastfeeding. Patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. Male patients must be surgically sterile or agree to use effective contraception. 10.Administration of any investigational drug within 28 days or 5 half lives, whichever is longer, prior to receiving the first dose of study treatment 11.Treatment with any of the following anti-cancer therapies: Radiation therapy, surgery or tumour embolisation within 14 days prior to the first dose of study medication Chemotherapy, immunotherapy, biologic therapy, investigational therapy within 28 days or 5 half-lives of a drug (whichever is longer) prior to the first dose of study medication. 12.Peripheral neuropathy of grade 2 or more. 13.Any on-going toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia. 14.Other severe or uncontrolled systemic disease or evidence of any other significant clinical disorder or lab finding that makes it undesirable for the patient to participate in the study. 15.Any psychological, familial, sociological or geographical consideration potentially hampering compliance with the study protocol and follow up schedule; those considerations should be discussed with the patient before registration in the trial. 16.Known HIV or other chronic immunosuppressive disease. 17. QTc that is immeasurable or >480 msec on screening ECG. (Note: If a subject has a QTc interval >480 msec on screening ECG, the screening ECG may be repeated twice (at least 24 hours apart). The average QTc from the three screening ECGs must be <
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to investigate whether pazopanib increases the overall survival time for patients with relapsed or progressive disease; in comparison to the current standard treatment, paclitaxel.;Secondary Objective: The secondary objectives of the study are to measure the following for pazopanib in comparison to the current standard treatment, paclitaxel: -Toxicity -Clinical benefit at 12 weeks -Progression free survival time -Clinical benefit at 24 weeks -Quality of Life;Primary end point(s): Overall survival.;Timepoint(s) of evaluation of this end point: The primary endpoint is overall survival. Data relating to any patient death that occurs throughout the study period will be captured via the Case Report Form (CRFs), both during the treatment period and active follow up. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary end points of the study are to measure the following for pazopanib in comparison to the current standard treatment, paclitaxel: -Toxicity -Clinical benefit at 12 weeks -Progression free survival time -Clinical benefit at 24 weeks -Quality of Life;Timepoint(s) of evaluation of this end point: -Toxicity will be assessed at all study visits while the patient is receiving treatment and until any ongoing toxicity is resolved. -Clinical benefit will be assessed after 12 and 24 weeks on treatment. Assessment will be by CT scans/MRI as appropriate and the tumour response (stable disease (SD), partial response (PR) or complete response (CR) will be reported in accordance with RECIST 1.1. -Progression free survival will be assessed on an ongoing basis, by radiology and/or any other means of idenitification, or the opinion of the investigator. -Quality of Life (QoL)will be assessed continuously throughout the trial. QoL questionnaires will be collected at baseline (Week 1), and at Weeks 9, 17, 25, 37, 49, 61, 73, 85 and 97. | — |
Countries
United Kingdom
Contacts
Public ContactResearch & Development
NHS Greater Glasgow & Clyde
Outcome results
None listed