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

• Status: Terminated
• Trial end date: 2012-03-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of the study is to assess the efficacy of the combination consisting of gemcitabine/cisplatin and panitumumab in patients with urothelial carcinoma and 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: WiSP Wissenschaftlicher Service Pharma GmbH
• Collaborators: Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH; Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH
• Treatments: Antibodies, Monoclonal; Cisplatin; Gemcitabine; Panitumumab

Criteria

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