Relapsed or progressive transitional cell carcinoma of the urothelium Cancer Malignant neoplasms of urinary tract
Conditions
Interventions
Patients are randomised on a 1:1 basis to either:
1. Pazopanib 800mg orally once daily until disease progression or patient toxicity or patient choice
2. Paclitaxel 80
Sponsors
NHS Greater Glasgow and Clyde (UK)
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 5.4. Absolute neutrophil count (ANC) =1500/mm3 without growth factor support 5.5. Platelets = 100,000/mm3 5.6. Urine protein to creatinine ratio (UPC) < 110 mg/mmol (1g/g) (or total urinary protein < 1g/24hrs) 5.7. Activated partial thromboplastin time (APTT) =1.2 x ULN 5.8. International normalised ratio (INR) = 1.2 6. Signed and dated informed consent indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrolment 7. A negative pregnancy test for women of childbearing potential 8. Life expectancy of 3 months or more 9. Willingness and ability to comply with scheduled visits, treatment plans and laboratory tests and other study procedures 10. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
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 haematemis; 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. 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: are asymptomatic and 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 five half lives, whichever is longer, prior to receiving the first dose of study treatment 11. Treatment with any of the following anti-cancer therapies: 11.1. Radiation therapy, surgery or tumour embolisation within 14 days prior to the first dose of study medication 11.2. Chemotherapy, immunotherapy, biologic therapy, investigational therapy within 28 days or five 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 Human immunodeficiency v
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall survival | — |
Secondary
| Measure | Time frame |
|---|---|
| 1 Progression free survival 2 Clinical benefit (proportion of patients alive with stable disease, partial response or complete response) at 12 weeks after the start of treatment 3 Clinical benefit at 24 weeks after start of treatment 4 Toxicity according to Common Terminology Criteria for Adverse Events version 4 (CTCAE v4) 5 Qualiy of life assessed by FACT-Bl at weeks 1, 9, 17, 25, 37, 49, 61, 73, 85 and 97 | — |
Countries
Scotland, United Kingdom
Outcome results
None listed