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

This is an interventional treatment trial for Urinary Bladder Cancer Read More

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