PURO Panitumumab in Combination With Gemcitabine/Cisplatin in Advanced Urothelial Cancer

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