The primary aim of this trial is to establish the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of LDE225 given in combination with standard doses of paclitaxel in patients with advanced solid tumors. In addition, the preliminary anti-tumor activity of this combination will be assessed, in particular in ovarian cancer.
This is a multicenter, open label phase I dose-escalation trial of LDE225 administered once daily (OD) with Paclitaxel administered weekly for three weeks (days 1, 8, 15) in 28-day cycles in adult patients with advanced solid tumors that have progressed despite standard therapy. The trial will consist of three parts. In Part A (dose escalation following a standard 3+3 design), patients with previously treated advanced solid tumors will receive escalating doses of LDE225 in combination with standard Paclitaxel doses, to define the MTD and the RP2D of LED225 OD that can be given in combination with standard doses of Paclitaxel. Once the MTD and RP2D is established in 6 patients, then part B will start. Part B and C are expansion cohorts in patients with advanced platinum-resistant ovarian cancer (6 patients each) to further evaluate the safety of the combination and to assess for any preliminary antitumor activity. In Part B, any prior taxane therapy must have been administered on a 3-week schedule. In Part C, prior taxane therapy must have been administered on weekly schedule and has to be followed by a wash-out period of at least 6 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
400, 600 and 800 mg OD
80 mg/m2 (days 1, 8, 15)
Istituto Oncologico della Svizzera Italiana
Bellinzona, Switzerland
Kantonsspital Graubünden
Chur, Switzerland
Centre Pluridisciplinaire d'Oncologie CHUV
Lausanne, Switzerland
Kantonsspital St. Gallen
Sankt Gallen, Switzerland
Dose limiting toxicities (DLTs) of the combination of LDE225 with paclitaxel in patients with advanced solid tumors
Time frame: until up to 4 weeks after start of trial therapy
Frequency and severity of adverse events based on the Common Terminology Criteria for Adverse Events V.4.0 (CTCAE).
Time frame: expected average 3 months
Objective tumor responses based on RECIST 1.1 criteria.
Time frame: expected average 3 months
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