A pharmacokinetic and dose-escalating study of paclitaxel injection concentrate for nano-dispersion (PICN) alone and with carboplatin in patients with advanced solid tumors.

Abstract

2557 Background: PICN is a novel Cremaphor-free composite of paclitaxel nano-particles stabilized with polymer and lipid using Nanotecton Technology. The MTD of PICN alone was previously determined to be 295 mg/m2 iv every 3 weeks in a South Asian population. This study aimed to determine the pharmacokinetic (PK) profile of PICN alone and with carboplatin (C), and the MTD of PICN plus C. Methods: Patients (pt) with advanced solid malignancies and ECOG PS 0-1 were eligible. Part A was a PK study designed to examine cohorts of 3 pts, receiving PICN over 30 min at dose levels of 175, 260, and 295 mg/m2 every 3 weeks; PK were performed at pre-determined time-points. Part B used a ‘3+3’ dose escalation scheme, designed to determine the MTD of PICN (220, 260, and 295 mg/m2) when combined with C at AUC 6. Only standard anti-emetic pre-medications were used. Adverse events (AEs) were graded using CTCAE 4.0 and tumor response by RECIST 1.1. Results: A total of 18 evaluable pts (9 in Part A, 9 in Part B) were enrolled from 2 US academic centers. No infusion reactions were observed with PICN. No dose limiting toxicity (DLT) was observed in Part A. In Part B, the DLTs were G3 febrile neutropenia and G4 thrombocytopenia requiring platelet transfusion at PICN 260/C AUC 6. A total of 6 pts were treated at PICN 220/C AUC 6 with no DLT. G3 or worse AEs for all cycles were as follow: Part A, bilateral lower extremity weakness, neuropathy, anorexia and neutropenia; Part B, anemia, thrombocytopenia, neutropenia and empyema. Partial responses were observed in biliary(Part A; PICN 260 mg/m2), breast (Part B 220/6) and anal cancers (Part B 260/6). PK analysis showed dose-proportional increase in total plasma paclitaxel level. Conclusions: PICN alone was tolerable in the dose range evaluated. When administered with C AUC 6, the MTD of PICN was 220 mg/m2 administered every 3 weeks. Anti-cancer activity was observed in biliary, breast, and anal cancers. Final PK, toxicity and efficacy data of PICN alone and with C will be presented at the conference. Clinical trial information: NCT01304303.