An open-label, randomised, multicentre, phase II study to evaluate the efficacy of chemotherapy with gemcitabine and cisplatin in combination with the EGF receptor antibody panitumumab (GemCisP) versus GemCis in the first-line therapy of locally advanced/metastatic urothelial carcinoma in patients with wild-type HRAS - PURO - AB 23/09
- Conditions
- bladder cancerC67Malignant neoplasm of bladder
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 124
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
- 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
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Progression-free survival rate after 12 months.
- Secondary Outcome Measures
Name Time Method - Determination of best response (CR, PR and SD) rates in accordance with the RECIST criteria [ Time Frame: up to 18 weeks (until the end of treatment) ]<br>- Duration of response, progression-free and overall survival time [ Time Frame: 2 years (until the end of follow up) ] <br>- Documentation of adverse effects in accordance with the NCI CTC criteria [ Time Frame: up to 18 weeks (until the end of treatment) ]<br>- Documentation of quality of life on the basis of the EORTC questionnaire [ Time Frame: up to 18 weeks (until the end of treatment) ]<br>