Phase I Dose-escalating Study to Evaluate the Safety and Tolerability of LiPlaCis (Liposomal Cisplatin Formulation) in Patients With Advanced or Refractory Tumours
- Histological or cytological documented locally advanced or metastatic solid tumour
refractory to standard therapy or for which no curative therapy exists.
- Age >= 18 years.
- Life expectancy >= 3 months.
- ECOG performance status of 0 - 2.
- 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
- >= 4 weeks must have elapsed since patient received any radiotherapy, 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, blood transfusions or therapy
with G-CSF and GM-CSF. However, current use of erythropoietin will be permitted.
- Adequate condition as evidenced by the following clinical laboratory values:
- Absolute neutrophil count (ANC) >= 1,5 x 10E9/L
- Haemoglobin is at least 5,6 mmol/L
- Platelets >= 100 x 10E9/L
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2,5 x
ULN, in case of known liver metastases ALT and AST <= 5 x ULN
- Serum bilirubin <= 1,5 ULN
- Alkaline phosphatase <= 2,5 x ULN
- Creatinine and blood urea within normal limits and creatinine clearance within
normal limits (>= 60 mL/min Cr-EDTA clearance).
- Sexually active males and females of child-producing potential, must use adequate
contraception (oral contraceptives, intrauterine device or barrier method of
contraception in conjunction with spermicidal jelly or surgical sterile) 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 uncontrolled bleeding or bleeding diathesis (e.g., active peptic ulcer
- Any active infection requiring parenteral or oral antibiotic treatment.
- Known infection with human immunodeficiency virus (HIV) or hepatitis virus.
- Pre-existing renal insufficiency.
- 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
- Female patients who are pregnant or breast-feeding (pregnancy test with a positive
result before study entry).
- Unwilling or unable to follow protocol requirements.