Phase I/II Study to Evaluate the Safety and Tolerability of LiPlaCis in Patients With Advanced or Refractory Tumours

Inclusion Criteria

• •Histological or cytological documented locally advanced or metastatic solid tumour relapsed on 2 or more different prior therapies. From step 5 and extension phase, population limited to Skin Cancer patients (non screened) or metastatic Breast Cancer patients or metastatic castration-resistant prostate cancer patients screened sensitive to LiPlaCis.
• •Age \>= 18 years.
• •Life expectancy \>= 3 months.
• •ECOG performance status of 0 - 1.
• •Recovered to Grade 1 or less from acute toxicities of prior treatment.
• •\>= 6 months must have elapsed since patient received cisplatin.
• •\>= 4 weeks must have elapsed since patient received any investigational medicinal product.
• •\>= 4 weeks must have elapsed since patient received any radiotherapy(except for palliative radiotherapy on non-target lesions), or treatment with cytotoxic or biologic agents (\>=6 weeks for mitomycin or nitrosoureas). No hormonal treatment is allowed except treatment with corticosteroids at physiological dose and hormonal treatment with LHRH agonists for prostate cancer.
• •\>=2 weeks must have elapsed since any prior surgery or therapy with G-CSF and GM-CSF.
• •Adequate condition as evidenced by the following clinical laboratory values:
• •* Absolute neutrophil count (ANC) \>= 1,5 x 10E9/L
• •* Haemoglobin is at least 4,6 mmol/L
• •* Platelets \>= 75 x 10E9/L
• •* Serum bilirubin \<= 1,5 ULN
• •* Blood urea within normal limits, creatinine below upper normal limits and creatinine clearance within normal limits (\>= 60 mL/min Cr-EDTA clearance).In the case of hydronephrosis, renography must be considered prior to treatment with LiPlaCis. For signs of drainage obstacle, well-functioning renal excretion/effect and normal diuresis must be ensured, e.g. via a double-J catheter.
• •Sexually active males and females of child-producing potential, must use adequate contraception (oral contraceptives, intrauterine device or barrier method of contraception) for the study duration and at least six months afterwards.
• •Patient must understand the investigational nature of this study and sign an independent ethical committee (IEC) approved written informed consent form prior to any study related activities.
• •Active heart disease including myocardial infarction or congestive heart failure within the previous 6 months, symptomatic coronary artery disease, or symptomatic arrhythmias currently requiring medication.
• •Known or suspected active central nervous system (CNS metastasis). (Patients stable 8 weeks after completion of treatment for CNS metastasis are eligible).
• •Autoimmune disease.
• •Impending or symptomatic spinal cord compression or carcinomatous meningitis.
• •Pre-existing neuropathy, i.e., Grade \>1 neuromotor or neurosensory toxicity (as defined by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v4,0), except for abnormalities due to cancer.
• •Known hypersensitivity to cisplatin or liposomes.
• •Requiring immediate palliative treatment of any kind including surgery and/or radiotherapy(except for palliative radiotherapy on non-target lesions).
• •Female patients who are pregnant or breast-feeding (pregnancy test with a positive result before study entry).
• •Unwilling or unable to follow protocol requirements.
• •Previous progression on a platinum containing therapy.