A Phase II multi-center, non-randomized, open-label study of TKI258 in patients with either FGFR3 mutated or FGFR3 wild type advanced urothelial carcinoma.

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 4

Inclusion Criteria

1.Histological confirmation of transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis
* Locally advanced or metastatic disease
2. Archival tumor tissue available FGFR3 mutational status analysis
3. Documented progressive disease at baseline
4. At least one measurable site of disease as defined by RECIST
5. Previously treated with at least 1 but not more than 3 systemic cytotoxic regimens, at least one of the following: cisplatin, carboplatin,gemcitabine or taxane
6. WHO Performance Status * 2
7. Required baseline laboratory values:
* Absolute neutrophil count (ANC) * 1.5 x 109/L
* Platelets * 100 x 109/L
* Hemoglobin * 9.0 g/dL [5,58 mmol/L]
* AST/SGOT and ALT/SGPT * 3.0 x Upper Limit of Normal [ULN] (or AST/SGOT and ALT/SGPT * 5 x ULN if abnormal liver function is due to tumor involvement of the liver)
* Bilirubin * 1.5 x ULN
* Serum creatinine * 1.5 x ULN

Exclusion Criteria

1.Patients with known brain metastases or who have signs/symptoms attributable to brain
metastases.
2. History of another malignancy < three years prior to study entry, with the exception of adequate treated basal cell carcinoma, squamous cell carcinoma or non-melanomatous skin cancer, excised carcinoma in situ of the cervix, or adenocarcinoma of the prostate.
3. Anti-cancer therapy and radiation for palliation * 14 days prior to starting study drug.
4. Nitrosourea or mitomycin-C * 6 weeks prior to starting study drug.
5. Anti-cancer monoclonal antibody * 6 weeks prior to starting study drug.
6. Wide field radiotherapy * 4 weeks to starting study drug.
7. Major surgery * 2 weeks prior to starting study drug.
8. Any of the following concurrent severe and/or uncontrolled medical conditions:
a) Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
* History or presence of serious ventricular arrhythmias or serious atrial fibrillation
* Clinically significant bradycardia
* LVEF < 45 %
* myocardial infarction, severe/unstable angina, Coronary Artery Bypass Graft, Congestive Heart Failure, Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism within 6 months prior to study entry:
* Uncontrolled hypertension (Systolic BP * 160 mm Hg and/or Diastolic BP * 100 mm Hg), with or without anti-hypertensive medication. Initiation or adjustment
of antihypertensive medication(s) is allowed prior to study entry.
b) Previous pericarditis; clinically significant pleural effusion in the previous 12 months
or current ascites requiring two or more interventions/month
c) Impairment of gastrointestinal function that may alter the absorption of TKI258.
d) Known diagnosis of HIV infection.
e) History of alcoholism, drug addiction, or any psychiatric or psychological condition
f) Therapeutic doses of warfarin
g) Uncontrolled diarrhea * CTCAE grade 2
h) Pregnant or breast-feeding women.
i) Male or female not willing to use adequate contraceptive protection (when applicable)

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Overall Response (Complete responses (CR) or partial responses (PR)) Rate. CR<br /><br>and PR will be defined according to RECIST as per local assessment.</p><br>

Secondary Outcome Measures

Name	Time	Method

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