RATIONALE: Drugs used in chemotherapy, such as carboplatin and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vandetanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether giving carboplatin and gemcitabine hydrochloride is more effective with or without vandetanib as first-line therapy in treating urinary tract cancer. PURPOSE: This randomized phase II trial is studying giving carboplatin together with gemcitabine hydrochloride and to see how well it works when given with or without vandetanib as first-line therapy in treating patients with locally advanced or metastatic urinary tract cancer.
OBJECTIVES: Primary * To determine the antitumor activity (as measured by progression-free survival) of carboplatin and gemcitabine hydrochloride with versus without vandetanib as first-line treatment in patients with locally advanced or metastatic urothelial cell cancer who are not suitable to receive cisplatin. Secondary * To determine the safety, feasibility, and tolerability of these regimens in these patients. * To determine the objective response rate. * To determine the overall survival of patients treated with these regimens * To assess the change of size of measurable lesions at 9 weeks of study therapy. OUTLINE: This is a multicenter study. Patients are stratified according to relevant factors. Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive carboplatin IV over 30 minutes on day 1, gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and an oral placebo once daily on days 1-21. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. * Arm II: Patient receive carboplatin and gemcitabine hydrochloride as in arm I. Patients also receive oral vandetanib once daily on days 1-21. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Blood and urine samples may be collected for laboratory analysis at baseline and after completion of study. After completion of study treatment, patients are followed up at weeks 18, 26, 39, and 52. Peer Reviewed and Funded or Endorsed by Cancer Research UK.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
82
Beatson West of Scotland Cancer Centre
Glasgow, Scotland, United Kingdom
Wales Cancer Trials Unit
Cardiff, Wales, United Kingdom
Ayr Hospital
Ayr, United Kingdom
Royal Bournemouth General Hospital
Bournemouth, United Kingdom
Queens Hospital
Burton-on-Trent, United Kingdom
Velindre Hospital
City and County of Cardiff, United Kingdom
Western General Hospital
Edinburgh, United Kingdom
Calderdale Royal Infirmary
Halifax, United Kingdom
Huddersfield Royal Infirmary
Huddersfield, United Kingdom
The Royal Lancaster Infirmary
Lancaster, United Kingdom
...and 11 more locations
Progression Free Survival
Time to event PFS, follow-up to 1 year
Time frame: 1 year
Tolerability and feasibility
Rate of randomisation and safety profile of randomised patients
Time frame: 1 year
Objective response rate as assessed by RECIST criteria
Proportion of patients responding to treatment
Time frame: Up to 1 year
Overall survival
Patients will be followed up until death by using NHS flagging service.
Time frame: 2 years
Change in size of measurable lesions 9 weeks after start of chemotherapy
Time frame: 9 weeks
Toxicity during and after treatment as assessed by NCI CTCAE v 4.0
Time frame: 1 year
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