Inclusion Criteria:

- Histologically or cytologically confirmed, unresectable urothelial carcinoma of the
bladder or the upper urinary tract

- Wild-type HRAS

- Male and female subjects > 18 years of age

- General condition ECOG 0-1

- Life expectancy at least 12 weeks

- Women of child-bearing potential: negative pregnancy test and use of effective
contraception(oral contraceptive, coil); men: use of adequate male contraception
(condom) for up to 3 months after discontinuation of panitumumab therapy

- Locally advanced or metastatic disease (T3b,T4 and/or N+ and/or M+)

- At least one unidimensionally measurable lesion detectable in CT or MRI corresponding
to the RECIST criteria

- Adequate haematological, hepatic, renal and metabolic function parameters:

Leukocytes > 3000/mm³, ANC ≥ 1500/mm³, platelets ≥ 100,000/mm³, hemoglobin > 9 g/dl
Creatinine clearance ≥ 50 ml/min and serum creatinine ≤ 1.5 x upper limit of normal
Bilirubin ≤ 1.5 x upper limit of normal, GOT-GPT ≤ 2.5 x upper limit of normal in absence
of liver metastases, or ≤ 5 x upper limit of normal in presence of liver metastases, AP ≤
5 x upper limit of normal Magnesium ≥ lower limit of normal; calcium ≥ lower limit of
normal INR and PTT < 1.5 x the upper limit of the normal reference range

Exclusion Criteria:

- HRAS mutation

- Absence of any of the above-listed inclusion criteria

- Dialysis-dependence following nephrectomy

- Patients with cerebral tumours and/or cerebral metastases

- Clinically significant cardiovascular disease in (incl. myocardial infarction,
unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac
arrhythmia) ≤ 1 year before enrolment.

- Patients with uncontrolled hypertension; systolic blood pressure > 150 mmHg or
diastolic blood pressure > 90 mmHg despite optimal medical treatment

- History of interstitial lung disease, e.g. pneumonitis or pulmonary fibrosis or
evidence of interstitial lung disease on baseline chest CT scan.

- Patients with thrombotic or embolic events, such as stroke or pulmonary embolism

- Patients with recent or known history of haemorrhagic diathesis

- Known significant neurological or psychiatric disorders, including dementia and
epileptic seizures

- Serious inflammatory eye conditions, hearing impairment

- Pulmonary (pO2 < 60 mmHg), haemopoietic (e.g. serious bone marrow aplasia), hepatic
or renal disorders

- Patients with poorly controlled diabetes mellitus

- Serious bacterial or fungal infections (>grade 2 NCI CTC Version 3)

- Chronic hepatitis B or C; HIV infection

- Autoimmune disease

- Allergic reaction to one of the medications to be used

- Status post organ transplantation

- Status post autologous bone marrow transplantation or stem cell transplantation in
the 4 months prior to study commencement

- Manifest secondary malignancy or other form of cancer in the previous 5 years
(excluding basalioma, in situ cervical cancer, incidental prostatic cancer)

- Subject pregnant or breast feeding, or planning to become pregnant within 6 months
after the end of treatment

- Subject (male or female) is not willing to use highly effective methods of
contraception (per institutional standard) during treatment and for 3 months (male or
female) after the end of treatment (adequate: oral contraceptives, intrauterine
device or barrier method in conjunction with spermicidal jelly).

- Active participation in other clinical studies in the previous 4 weeks

- Prior systemic therapy with cytostatics or immunotherapeutic agents

- Concurrent use of other anticancer treatments after study commencement

- Intravesical chemotherapy in the previous 4 weeks

- Radiotherapy in the previous 4 weeks

- Previous radiotherapy in which all lesions to be used for the evaluation of tumour
response were irradiated

- Patients in a closed institution according to an authority or court decision