Carboplatin and Gemcitabine Hydrochloride With or Without Vandetanib as First-Line Therapy in Treating Patients With Locally Advanced or Metastatic Urinary Tract Cancer
Condition: Bladder Cancer; Transitional Cell Cancer of the Renal Pelvis and Ureter; Ureter Cancer; Urethral Cancer
MeSH terms: Urinary Bladder Neoplasms; Urethral Neoplasms; Carcinoma, Transitional Cell; Kidney Neoplasms; Ureteral Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): carboplatin; gemcitabine hydrochloride; vandetanib; Placebo
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Placebo of vandetanib tablet
Intervention MeSH terms: Carboplatin; Gemcitabine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: metastatic transitional cell cancer of the renal pelvis and ureter; regional transitional cell cancer of the renal pelvis and ureter; transitional cell carcinoma of the bladder; stage III bladder cancer; stage IV bladder cancer; anterior urethral cancer; posterior urethral cancer; urethral cancer associated with invasive bladder cancer; ureter cancer