Liposomal formulations are frequently used today in the treatment of cancer. LiPlaCis is the first targeted liposomal formulation with a tumour triggered release mechanism to undergo clinical development in oncology and it is expected that LiPlaCis will improve the therapeutic index of cisplatin compared to conventional cisplatin. Cisplatin is one of the most widely used drugs in the treatment of cancer due to its documented efficacy in a number of tumour types. Furthermore, it seems highly likely that cisplatin will remain an important drug in the future treatment of cancer. However, the drug is associated with a number of serious toxicities that complicates or necessitates discontinuation of therapy - e.g. need for pre-hydration, neurotoxicity, nausea and vomiting. Thus, there is a well-established need for improving cisplatin therapy in cancer patients. One option here is improving the formulation of the drug, so that a more selective up-take of cisplatin administered takes place at the tumour sites. Based on the results of the pre-clinical studies of LiPlaCis, it seems clear that LiPlaCis offers the potential to improve cisplatin therapy to the benefits of cancer patients. In a prematurely stopped Phase I Dutch study a Recommended Dose (RD) for a Phase II study was never reached which was the aim of the finished Phase I dose escalating part of this study for advanced or refractory solid tumors. In the Phase 2 part of this study, patients with advanced breast cancer with a biopsy examination showing a pattern compatible with sensitivity to LiPlaCis or patients with skin cancer will be included.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
LiPlaCis IV every 3 weeks on day 1, day 8
The Phase One Unit, The Finsen Centre, Rigshospitalet
Copenhagen, Denmark
Herlev & Gentofte Hospital
Herlev, Denmark
Nordsjællands Hospital Hillerød
Hillerød, Denmark
Vejle Sygehus
Vejle, Denmark
Maximum tolerated dose (MTD) and recommended dose (RD) by evaluating the safety and tolerability
Primary Objective: Assessment of adverse events and laboratory abnormalities
Time frame: one year
Maximum Observed Plasma Concentrations of platinum (Cmax)
Blood samples are obtained and plasma concentrations of total LiPlaCis-derived platinum are determined using a validated atomic absorption spectrometry method.
Time frame: Prior to the initial dose on day 1, day 8 and 15 and 5 min before end of infusion, 5 min, 0,5, 1, 3, 7, 24, 48, 72 hours post dose
Concentration of platinum (Pt-DNA)
Tumor and normal tissue biopsies are obtained concentrations of platinum are determined using a validated method.
Time frame: Prior to the initial dose on day 1and 24 hours after
Area Under the Plasma - Time Concentration Curve (AUC)
Blood samples are obtained and plasma concentrations of total LiPlaCis-derived platinum are determined using a validated atomic absorption spectrometry method.
Time frame: Prior to the initial dose on day 1, day 8 and 15 and 5 min before end of infusion, 5 min, 0,5, 1, 3, 7, 24, 48, 72 hours post dose
Elimination half-life of platinum (T½)
Blood samples are obtained and plasma concentrations of total LiPlaCis-derived platinum are determined using a validated atomic absorption spectrometry method.
Time frame: Prior to the initial dose on day 1, day 8 and 15 and 5 min before end of infusion, 5 min, 0,5, 1, 3, 7, 24, 48, 72 hours post dose
Total body clearance of platinum (Cl)
Blood samples are obtained and plasma concentrations of total LiPlaCis-derived platinum are determined using a validated atomic absorption spectrometry method.
Time frame: Prior to the initial dose on day 1, day 8 and 15 and 5 min before end of infusion, 5 min, 0,5, 1, 3, 7, 24, 48, 72 hours post dose
Volume of distribution of platinum at steady state (Vss)
Blood samples are obtained and plasma concentrations of total LiPlaCis-derived platinum are determined using a validated atomic absorption spectrometry method.
Time frame: Prior to the initial dose on day 1, day 8 and 15 and 5 min before end of infusion, 5 min, 0,5, 1, 3, 7, 24, 48, 72 hours post dose
Therapeutic efficacy of LiPlaCis (Efficacy Endpoint)
Response and progression is evaluated using internationally accepted response criteria and definitions proposed by the RECIST criteria.
Time frame: Tumor Assessed every 6 weeks until and at end of treatment, with an expected average of 3 treatment cycles (9 weeks)
Progression Free Survival
PFS for patients at dose step 5 and up by Response and progression evaluated using internationally accepted response criteria and definitions proposed by the RECIST criteria.
Time frame: one year after end of treatment
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