In the first phase, 10-20 patients will be enrolled and treated with 300-520 mg BID of AXL1717 (picropodophyllin) for 28 days. The primary endpoint of the first phase is to determine the recommended Phase 2 dose (RP2D) of AXL1717 and to assess the safety and toxicity of AXL1717. The study has a 3+3 design and the first cohort will be treated with 400 mg AXL1717 BID for 28 days repeated in up to 5 cycles.

Picropodophyllin (PPP) effectively inhibited human Rhabdomyosarcoma cell proliferation in anchorage dependent assay on plastic dishes. Proliferation potential decreased in a dose-dependent manner (cells were treated with increasing doses of PPP (0–3 μM) and the effects of growth arrest were significant after 72 h of treatment. Effective, the subtoxic concentration was estimated to be 0.1 μM for both RH30 cells and RD treated for 72 h. Similarly, PPP inhibited colony formation on soft agar in an anchorage independent assay. Next, was tested the effect of PPP on cell viability/apoptosis and cell cycle. In this experiment, flow cytometric measurement (FACS-based PI staining and Annexin V binding assay) was used to quantify the extent of apoptosis in the total cell population. 24-h exposure to PPP caused a dose-dependent decrease in number of alive cells and increase in the percentage of late apoptotic cells (FITC+, PI+) beginning from 0.5 μM and higher doses of PPP ≥ 2 μM, lead to massive apoptosis and cell death.