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
- Conditions
- ocally advanced/metastatic urothelial carcinomaMedDRA version: 12.1Level: LLTClassification code 10046721Term: Urothelial carcinoma bladder stage IIIMedDRA version: 12.1Level: LLTClassification code 10046722Term: Urothelial carcinoma bladder stage IVMedDRA version: 12.1Level: LLTClassification code 10046724Term: Urothelial carcinoma ureter localMedDRA version: 12.1Level: LLTClassification code 10046725Term: Urothelial carcinoma ureter metastatic
- Registration Number
- EUCTR2009-015119-42-DE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
• Histologically or cytologically confirmed 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this explorative study is to assess the efficacy of the combination consisting of gemcitabine/cisplatin and panitumumab in patients with wild-type HRAS (non-mutated status). The progression-free survival rate at 12 months will be compared to expectations derived from historical data, which are verified by a randomised control group without the antibody.;Secondary Objective: •Determination of tumour response <br>•Duration of response<br>•Overall survival <br>•Documentation of adverse effects<br>•Quality of life survey<br>;Primary end point(s): Progression-free survival rate after 12 months.
- Secondary Outcome Measures
Name Time Method