PLUTO - (pazopanib versus paclitaxel in relapsed urothelial tumours) A Randomised Phase II study investigating pazopanib vs weekly paclitaxel in relapsed or progressive Transitional Cell Carcinoma (TCC) of the urothelium

Phase 1

• Conditions: 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: Transitional cell carcinoma of the bladder stage unspecified System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.0 Level: PT Classification code 10044407 Term: Transitional cell cancer of the renal pelvis and ureter System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-001841-34-GB
• Lead Sponsor: HS Greater Glasgow Health Board

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-11-21
• Study Completion: 2016-07-06
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 131

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 < 12 months prior to documented disease progression). The regimen must have included either cisplatin or carboplatin. Patients who have had two platinum containing regimens are eligible if one of these was given peri-operatively, and provided that there was a chemotherapy-free interval of at least 12 months between completing the 1st course and commencing the second course of chemotherapy. Chemotherapy given during radical radiotherapy as a radiosensitizer will not be considered as a chemotherapy treatment for the purposes of study eligibility. 3.Age = 18 years. 4.Measurable disease by RECIST 1.1. 5.Adequate organ function as defined by the following criteria: •Total serum bilirubin =1.5 x upper level of normal (ULN). •Serum transaminases <2.5 x ULN. Concomitant elevations of transaminases and bilirubin are not permitted. •Creatinine clearance >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) < 110 mg/mmol (1g/g) (or total urinary protein < 1g/24hrs) •Activated partial thromboplastin time (APTT) =1.2 x ULN •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.ECOG performance status of 0 or 1.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 42
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 98

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 <

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.