Phase I Study With Sorafenib in Addition to Vinflunine in Metastatic Transitional Cell Carcinoma of the Urothelial Tract
Condition: Urothelial Carcinoma; Bladder Cancer; Renal Pelvis Cancer; Ureter Cancer; Urethra Cancer
MeSH terms: Carcinoma; Carcinoma, Transitional Cell; Ureteral Neoplasms; Pelvic Neoplasms; Urethral Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      This study aims to analyse the tolerability (side effects and safety) with standard treatment
      (Javlor®) with the addition of a second anti-tumour drug: sorafenib (Nexavar®). This is the
      first time this treatment combination is studied in humans. Samples of blood, urine and
      tumour tissues will be analysed for molecular biomarkers. These biomarkers may potentially
      help us in the future in predicting whether a patient will benefit or not from the cancer
      treatment. The study also aims to investigate if a newer imaging method, called PET-CT
      (positron emission tomography-computed tomography), at an earlier stage (than a normal CT
      scan) can identify patients who will benefit from the given treatment.
    

Detailed description: 
      Objectives

        -  To explore the safety of sorafenib in combination with vinflunine in patients with
           transitional cell carcinoma of the urothelial tract and to define a recommended phase II
           dose for this treatment combination

        -  To correlate early tracer 18F-FDG-PET/CT functional imaging readouts with standard
           RECIST (version 1.1) evaluations with the intention to explore new endpoints for
           targeted therapy

        -  To find predictive tumour tissue biomarkers for sorafenib/vinflunine treatment

        -  To evaluate serum and urine markers of apoptosis as potential markers of
           sorafenib/vinflunine treatment

      Rationale/Goal

      To evaluate the tolerability and activity of sorafenib combined with vinflunine in patients
      with advanced or metastatic urothelial cancer.

      Tumour biopsies will be collected before and after one cycle of therapy. The translational
      part of this study aims to explore the predictive value of a number of biomarkers related to
      the targeted properties of sorafenib and presumptive markers for vinflunine treatment.

      In addition, the predictive value of an early functional imaging tracer 18F-FDG-PET/CT will
      be evaluated.
    

Intervention name(s): Vinflunine; Sorafenib
Intervention type(s): Drug; Drug
Intervention description(s): Vinflunine (Javlor®, Pierre Fabre Pharma): 320 mg/m2 I.V., day 1, repeated every 21 days for patients with PS 0, adequate renal (creatinine clearance >60 ml/min) and hepatic function (as described in the inclusion criteria). PLEASE NOTE THAT THE 320 mg/m2 ARM IS CLOSED FOR RECRUITMENT.
For patients with PS 1, or age 75 to 80 years, or exposed to radiation of the lower pelvis region, or with impaired renal function (creatinine clearance 40-60 ml/min) but adequate hepatic function (as described in the inclusion criteria), the dose of vinflunine is 280 mg/m2 I.V. day 1, repeated every 21 days.; Sorafenib (Nexavar®, Bayer HealthCare) daily dosage from day 2 through day 21 (repeated every 21 days):
Step 1: 400 mg P.O. (i.e. one (1) tablet 200 mg morning and evening, 1+0+1) Step 2: 600 P.O. (i.e. one (1) tablet 200 mg morning and two tablets evening, 1+0+2) Step 3: 800 mg P.O. (i.e. two (2) tablets 200 mg morning and evening, 2+0+2) Doses of sorafenib higher than 400 mg P.O. b.i.d. are not allowed.
Other intervention name(s): Javlor; Nexavar
Intervention MeSH terms: Sorafenib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment